I can't end the account of the events of 2001 without noting a small but significant personal change for me. I stood down as the Pompe representative on the AGSD-UK Executive. Partly because I was just worn out with it really. Partly because I had always seen my involvement as finite - I would do it until a treatment was available. That day was was now not so far off. And partly again because I was in the happy position of having a good successor in Allan Muir.
I've already sung Allan's praises once, so I won't embarrass him by doing it again. Except to note that he is one of those people who seems to radiate calm, when everyone else is in a flap. A quality I can only admire.
From now on, the rest of this blog (at least the bits written by me) will be somewhat detached from the UK scene. I retained my involvement with the IPA for another couple of years though (before cunningly diverting that to Allan too).
I therefore only have first-hand experience of two more years - 2002 and 2003.
Showing posts with label AGSD-UK. Show all posts
Showing posts with label AGSD-UK. Show all posts
Sunday, 17 January 2010
Thursday, 7 January 2010
Oxford 2000- part 2
AGSD-UK's Oxford 2000 conference (part 2)
Aside from the researchers we also had a strong representation from Genzyme and Pharming (who were the sponsors of the conference). In attendance were Jan van Heek, Gene Williams, Willem va Weperen and Phillipe Houten (I'm guessing here -I forgot to write Phillipe's second name down - d'oh!).
The first two had attended an IPA executive meeting the night before and had expressed a desire to be more open and communicative with the patient community. I therefore gave them the opportunity to answer a few of the questions that have been in people's minds since the switch to the CHO method of production: are there any differences in the results for the two methods? what are the benefits to us? What are the time-scales for trials? What is the availability of enzyme?
Genzyme: ERT is working and this is very encouraging. The question for us now is how can enough enzyme be made for more trials and beyond. It is good to know that, from Genzyme's experience, it is possible to get Government/insurance to pay for such products.
It was a difficult decision to switch manufacturing from the rabbits to cell culture. We have not been good at communicating this and in future would like to work better with patient groups.
We know that the product works and now need to work on appropriate doses etc. Time lines are under review and more questions arise as we go along. We promise to publicise any changes.
Questions
Q: We know that the milk based enzyme is efficient and non-toxic. can it not be made commercially viable? There is as yet no data for the cell-based enzyme.
A: We have looked at the unpublished data from Y T Chen and our believe that both products will behave similarly is supported by the data. (A. Reuser commented that tests with mice had shown no differences, however there was no comparison with humans yet. As the two trials had been set up differently, it was difficult to make an exact comparison - the types of patient, doses etc. may have been different, amongst other uncertainties. Conclusion - there is no evidence that suggests that they don't work equally well.)
In June, in Boston, all sorts of experts convened and reviewed the data. It was concluded that more trials were needed to satisfy the requirements of the regulatory authorities.
Lots of enzyme is needed and manufacturing must be scaled up dramatically
Q: Will it be easier to produce commercial quantities using cell manufacture?
A: Easier and faster. We have 60 different people working on the Pompe programme. The uncertainties are that we have no manufacturing capacity yet and no regulatory approval yet.
Q: Why not do trials which would be approved quicker?
A: Can't do it until ERT is proved to work, to the satisfaction of the regulatory authorities. At the beginning we didn't know the dose that would be required. A lot of material is needed to be effective, therefore a large manufacturing capacity is required. At least 50 people working on doing that.
We decided that this way was faster, more durable and gave more product to get to patients.
The key now is to get trials started to get us to the first end point - regulatory approval.
We need to select patients, treat them and then analyse and present the esults. All that takes time.
We now understand the importance of getting timely information to patients.
We are meeting with the FDA in October to discuss the next trial.
Q: Is this just for the USA?
A: Our intention is that the data will be produced in such a way that it is acceptable to all the different authorities. It will be a multi-centre trial in around 5 locations - not confined to the USA. We will communicate details to patient groups via the IPA.
Q: What are the plans for future trials?
A: The constraint is supply of enzyme. There may not be enough until late 2001. this is under discussion and review. We are working hard on this issue.
Q: Is the switch to CHO the solution to the problem of enzyme availability or the cause?
A: The solution. It will be quicker.
Q: What will happen to the patients receiving the rabbit milk enzyme at the moment?
A: We met some of the patients in Rotterdam. We are committed to provide the rabbit enzyme to them until 2001 [implication was until CHO supplies are available - KOD].
Q: In the early days we were told that rabbits could produce enough enzyme, then that cows would be used. Is that off the agenda now?
A: We think that there will be enough CHO capacity to meet demand. The cow platform is being preserved and the rabbit line just in case the CHO production does not work. All you can do is to make the best decision you can on the basis of the available data - and at the moment that means CHO.
Q: Would it be better to develop the products in parallel?
A: We've kept the one we don't want to implement as the back-up. If we used it we'd need to go back to the start with the regulatory authorities. However we do not expect CHO production to fail at this stage.
Q: Is it still worth getting regulatory approval for the rabbits on a small scale adult trial?
A: We are convinced that the data available shows proof of principle. However we have also concluded that the regulatory bodies would not give approval on the basis of the existing data. The big issue for us is how can we increase the availability of the product. CHO is the fastest way of doing this.
Q: Any information on costs?
A: Need to show treatment works first of all. Have experience of persuading insurance companies/governments to pay for ERT.
Q: Can you give information on trial dates?
A: This is ongoing. Earliest will be early 2001, followed by another 6-9
months later.
Q: Allowing for all obstacles how long till regulatory approval?
A: At least 5 years for all approvals.
Aside from the researchers we also had a strong representation from Genzyme and Pharming (who were the sponsors of the conference). In attendance were Jan van Heek, Gene Williams, Willem va Weperen and Phillipe Houten (I'm guessing here -I forgot to write Phillipe's second name down - d'oh!).
The first two had attended an IPA executive meeting the night before and had expressed a desire to be more open and communicative with the patient community. I therefore gave them the opportunity to answer a few of the questions that have been in people's minds since the switch to the CHO method of production: are there any differences in the results for the two methods? what are the benefits to us? What are the time-scales for trials? What is the availability of enzyme?
Genzyme: ERT is working and this is very encouraging. The question for us now is how can enough enzyme be made for more trials and beyond. It is good to know that, from Genzyme's experience, it is possible to get Government/insurance to pay for such products.
It was a difficult decision to switch manufacturing from the rabbits to cell culture. We have not been good at communicating this and in future would like to work better with patient groups.
We know that the product works and now need to work on appropriate doses etc. Time lines are under review and more questions arise as we go along. We promise to publicise any changes.
Questions
Q: We know that the milk based enzyme is efficient and non-toxic. can it not be made commercially viable? There is as yet no data for the cell-based enzyme.
A: We have looked at the unpublished data from Y T Chen and our believe that both products will behave similarly is supported by the data. (A. Reuser commented that tests with mice had shown no differences, however there was no comparison with humans yet. As the two trials had been set up differently, it was difficult to make an exact comparison - the types of patient, doses etc. may have been different, amongst other uncertainties. Conclusion - there is no evidence that suggests that they don't work equally well.)
In June, in Boston, all sorts of experts convened and reviewed the data. It was concluded that more trials were needed to satisfy the requirements of the regulatory authorities.
Lots of enzyme is needed and manufacturing must be scaled up dramatically
Q: Will it be easier to produce commercial quantities using cell manufacture?
A: Easier and faster. We have 60 different people working on the Pompe programme. The uncertainties are that we have no manufacturing capacity yet and no regulatory approval yet.
Q: Why not do trials which would be approved quicker?
A: Can't do it until ERT is proved to work, to the satisfaction of the regulatory authorities. At the beginning we didn't know the dose that would be required. A lot of material is needed to be effective, therefore a large manufacturing capacity is required. At least 50 people working on doing that.
We decided that this way was faster, more durable and gave more product to get to patients.
The key now is to get trials started to get us to the first end point - regulatory approval.
We need to select patients, treat them and then analyse and present the esults. All that takes time.
We now understand the importance of getting timely information to patients.
We are meeting with the FDA in October to discuss the next trial.
Q: Is this just for the USA?
A: Our intention is that the data will be produced in such a way that it is acceptable to all the different authorities. It will be a multi-centre trial in around 5 locations - not confined to the USA. We will communicate details to patient groups via the IPA.
Q: What are the plans for future trials?
A: The constraint is supply of enzyme. There may not be enough until late 2001. this is under discussion and review. We are working hard on this issue.
Q: Is the switch to CHO the solution to the problem of enzyme availability or the cause?
A: The solution. It will be quicker.
Q: What will happen to the patients receiving the rabbit milk enzyme at the moment?
A: We met some of the patients in Rotterdam. We are committed to provide the rabbit enzyme to them until 2001 [implication was until CHO supplies are available - KOD].
Q: In the early days we were told that rabbits could produce enough enzyme, then that cows would be used. Is that off the agenda now?
A: We think that there will be enough CHO capacity to meet demand. The cow platform is being preserved and the rabbit line just in case the CHO production does not work. All you can do is to make the best decision you can on the basis of the available data - and at the moment that means CHO.
Q: Would it be better to develop the products in parallel?
A: We've kept the one we don't want to implement as the back-up. If we used it we'd need to go back to the start with the regulatory authorities. However we do not expect CHO production to fail at this stage.
Q: Is it still worth getting regulatory approval for the rabbits on a small scale adult trial?
A: We are convinced that the data available shows proof of principle. However we have also concluded that the regulatory bodies would not give approval on the basis of the existing data. The big issue for us is how can we increase the availability of the product. CHO is the fastest way of doing this.
Q: Any information on costs?
A: Need to show treatment works first of all. Have experience of persuading insurance companies/governments to pay for ERT.
Q: Can you give information on trial dates?
A: This is ongoing. Earliest will be early 2001, followed by another 6-9
months later.
Q: Allowing for all obstacles how long till regulatory approval?
A: At least 5 years for all approvals.
Wednesday, 6 January 2010
Oxford 2000 part 1
Every year I say the Pompe's workshop was the biggest and best so far, and this year's was no exception. Just under 50 people attended the workshop,held on Saturday 9 September 2000 at the Oxford Belfry Hotel.
As well as UK patients and families, we also had participants from Denmark,The Netherlands, Germany and the USA. These included some representatives from Genzyme and Pharming, of whom more later.
To begin with, we had the star of the show - Ans van der
Ploeg. She was accompanied by Arnold Reuser, Marian
Kroos and Hannerieke van den Hout. Yes,we had the cream
of Pompe's research attending the one little meeting. I can't
tell you how pleasing it was to see not only the research
leaders but also Marian Kroos, whose name has co-authored
many research papers and has been Arnold Reuser's
collaborator for many years, and Hannerieke van den Hout,
who has been deeply involved in the clinical trial and is the
'first author' on the Lancet paper.
I introduced the proceedings by mentioning the change in
attitude towards enzyme replacement therapy for Pompe's,
from it being effectively a dead duck to a successful
clinical trial. I pointed out that this was due to the work
carried out in the Netherlands, in large part by people
present today.
Dr van der Ploeg gave a good account of the ERT trial
on infants. She began by saying that she had said in every
talk for the last 10 years that enzyme replacement therapy
was a possibility. Now, for the first time, she could
present real evidence of it working.
She presented the results of 36 weeks of treatment for
the 4 infants. The inclusion criteria were: showing
symptoms of Pompe's, including heart enlargement; less
than 10 months of age; alpha-glucosidase deficiency;
muscle biopsy diagnosis.
The ages at diagnosis were 1, 4, 0.5 and 6 months, and
at inclusion, 3, 7,2.5 and 8 months.
Patients 2 and 4 had lost a great deal of muscle function
and required oxygen.
After 12 weeks, all 4 babies had an alpha glucosidase
activity within the 'normal' (i.e. non-Pompe's) range.
Muscle biopsies (images shown) illustrated that glycogen
storage had been markedly reduced. Heart size was
also reduced.
Muscle function showed improvement. One child is still on
a ventilator and one is now walking.
Conclusions:
The treatment is generally well-tolerated.
The treatment prolongs life.
Therapeutic effects were observed.
Muscle function and cardio-respiratory function were both
stimulated.
And perhaps most importantly - it is easier to prevent than
to cure, therefore treatment should be started early.
[Applause]
Questions
Q: The dose was increased 3-fold during the trial. Are
you satisfied with the current dose?
A: Yes. Enzyme activity is normalised, which is a good
sign that the dose is correct.
Q: Is it possible that not all muscle activity would be
recovered?
A: Yes, it is possible - some muscle fibres may be
beyond repair. Recovery may be a very long process
for severely affected patients.
Q: Did any patients show an antibody response to
the enzyme?
A: Yes but this did not appear to have an effect on
the treatment.
Q: Does enzyme get to the lysosomes?
A: Yes - we know this because glycogen is removed
from the lysosomes by the enzyme.
Q: Is it possible that measuring enzyme activity may
overstate the amount there, since you may be measuring
enzyme that is in the rest of the cell too?
A: Theoretically this is possible, however alpha
glucosidase is only active at the acid pH of the lysosomes,
not the neutral pH of the rest of the cell. In the end, the
best measure of enzyme activity is that the glycogen is
removed and muscle function improves. This has been
shown by the trial.
Q: What the implications for the late onset types?
A: Too early to say but treatment holds promise. It will
be a long process but hopeful for the future for ALL
Pompe's patients.
Q: Can you say anything about the status of juvenile trials?
A: The trial has started but it will take longer than with the
infants to make certain that measurements and improvements
are actually due to the treatment. There is a need to gather
reliable statistics and data.
Q: Is a controlled diet more important in the later onset forms?
A: There are many hypotheses. It is certainly very important
to have enough protein for muscles. Keeping busy/moving
is a good way to help muscle strength.
[Prolonged applause]
As well as UK patients and families, we also had participants from Denmark,The Netherlands, Germany and the USA. These included some representatives from Genzyme and Pharming, of whom more later.
To begin with, we had the star of the show - Ans van der
Ploeg. She was accompanied by Arnold Reuser, Marian
Kroos and Hannerieke van den Hout. Yes,we had the cream
of Pompe's research attending the one little meeting. I can't
tell you how pleasing it was to see not only the research
leaders but also Marian Kroos, whose name has co-authored
many research papers and has been Arnold Reuser's
collaborator for many years, and Hannerieke van den Hout,
who has been deeply involved in the clinical trial and is the
'first author' on the Lancet paper.
I introduced the proceedings by mentioning the change in
attitude towards enzyme replacement therapy for Pompe's,
from it being effectively a dead duck to a successful
clinical trial. I pointed out that this was due to the work
carried out in the Netherlands, in large part by people
present today.
Dr van der Ploeg gave a good account of the ERT trial
on infants. She began by saying that she had said in every
talk for the last 10 years that enzyme replacement therapy
was a possibility. Now, for the first time, she could
present real evidence of it working.
She presented the results of 36 weeks of treatment for
the 4 infants. The inclusion criteria were: showing
symptoms of Pompe's, including heart enlargement; less
than 10 months of age; alpha-glucosidase deficiency;
muscle biopsy diagnosis.
The ages at diagnosis were 1, 4, 0.5 and 6 months, and
at inclusion, 3, 7,2.5 and 8 months.
Patients 2 and 4 had lost a great deal of muscle function
and required oxygen.
After 12 weeks, all 4 babies had an alpha glucosidase
activity within the 'normal' (i.e. non-Pompe's) range.
Muscle biopsies (images shown) illustrated that glycogen
storage had been markedly reduced. Heart size was
also reduced.
Muscle function showed improvement. One child is still on
a ventilator and one is now walking.
Conclusions:
The treatment is generally well-tolerated.
The treatment prolongs life.
Therapeutic effects were observed.
Muscle function and cardio-respiratory function were both
stimulated.
And perhaps most importantly - it is easier to prevent than
to cure, therefore treatment should be started early.
[Applause]
Questions
Q: The dose was increased 3-fold during the trial. Are
you satisfied with the current dose?
A: Yes. Enzyme activity is normalised, which is a good
sign that the dose is correct.
Q: Is it possible that not all muscle activity would be
recovered?
A: Yes, it is possible - some muscle fibres may be
beyond repair. Recovery may be a very long process
for severely affected patients.
Q: Did any patients show an antibody response to
the enzyme?
A: Yes but this did not appear to have an effect on
the treatment.
Q: Does enzyme get to the lysosomes?
A: Yes - we know this because glycogen is removed
from the lysosomes by the enzyme.
Q: Is it possible that measuring enzyme activity may
overstate the amount there, since you may be measuring
enzyme that is in the rest of the cell too?
A: Theoretically this is possible, however alpha
glucosidase is only active at the acid pH of the lysosomes,
not the neutral pH of the rest of the cell. In the end, the
best measure of enzyme activity is that the glycogen is
removed and muscle function improves. This has been
shown by the trial.
Q: What the implications for the late onset types?
A: Too early to say but treatment holds promise. It will
be a long process but hopeful for the future for ALL
Pompe's patients.
Q: Can you say anything about the status of juvenile trials?
A: The trial has started but it will take longer than with the
infants to make certain that measurements and improvements
are actually due to the treatment. There is a need to gather
reliable statistics and data.
Q: Is a controlled diet more important in the later onset forms?
A: There are many hypotheses. It is certainly very important
to have enough protein for muscles. Keeping busy/moving
is a good way to help muscle strength.
[Prolonged applause]
Back on track - progress on the real treatment
After that excursion to plant Novazyme, we go back to the development of a treatment for Pompe disease.
The results of the clinical trials, corporate shenanigans and subsequent buy-out of Synpac had left patients feeling uneasy. The Rotterdam (and Duke) results had been promising yet the corporate turbulence had confused the picture. What exactly was going on? Could we still rely on genzyme? What was going to happen next?
At the AGSD-UK conference, held in Oxford in September 2000, we got some answers.
An attached IPA meeting ensured a good international presence and genzyme sent over a high-powered delegation, including Jan van Heek, second in command of the company. That itself sent a message that they meant business.
What follows in the next couple of posts is the account that originally appeared on GSDNet at the time, complete with some contemporary photographs.
The results of the clinical trials, corporate shenanigans and subsequent buy-out of Synpac had left patients feeling uneasy. The Rotterdam (and Duke) results had been promising yet the corporate turbulence had confused the picture. What exactly was going on? Could we still rely on genzyme? What was going to happen next?
At the AGSD-UK conference, held in Oxford in September 2000, we got some answers.
An attached IPA meeting ensured a good international presence and genzyme sent over a high-powered delegation, including Jan van Heek, second in command of the company. That itself sent a message that they meant business.
What follows in the next couple of posts is the account that originally appeared on GSDNet at the time, complete with some contemporary photographs.
Saturday, 12 December 2009
The 1997 AGSD-UK conference: an international gathering
The 1997 AGSD-UK conference took place on 25 May, in Slough, near London. Coincidentally, I used to live in Slough and managed to get the Mayor, Lakhbir Minhas, to come an open the conference, which ensured some local news coverage and also gave a suitable sense of occasion. I also managed to blag a few boxes of chocolate bars from my old employer. Let's just say that we were well prepared for work, rest and playing. And just as well, for this was to be a remarkable conference, for all sorts of reasons.
A report from the Slough Observer! Photo shows Mayor Minhas, Me, Elaine & Euan, Arnold Reuser and Ann Philips. It also contains my embryonic daughter, Catriona who was born in December. We got the CVS all-clear on the drive down.
Firstly, there were a number of international attendees, mainly from the Pompe field. From memory, Gerd Hassler from Germany, Bob Morrison from Australia, Ross Harvey (jr's brother),Randall House and YT Chen from the USA and Gerben Moolhuizen and Arnold Reuser from the Netherlands. Many of us had 'met' online, so in a way it was a GSDNet conference too! In retrospect, this really helped to cement the development of a Pompe community.
There were a series of remarkable presentations too. Arnold Reuser gave a talk on the latest developments in ERT and was helped in the following Q & A session by Gerben Moolhuizen.
That was obviously exciting. However, the following presentation by YT Chen was a real show-stopper. Yt presented his work involving Japanese quails, an unusual choice of experimental animal, explained by the fact that they have the bird equivalent of Pompe disease.
The affected birds were unable to move their wings, or to right themselves after being turned over. After 3 weeks treatment with enzyme produced in YT's lab (at Duke University USA) one of the birds was able to fly - and was only stopped after it hit a light stand! Analysis showed that their heart and liver had returned to normal and that their skeletal muscle, while still containing some glycogen, showed obvious signs of improvement - and, more to the point, fairly spectacular evidence of recovered function!
It was a remarkable double-whammy for everyone in that room. ERT was being developed - and there were the people developing it, right in front of us, answering questions. Not only that but a researcher had come from the US with dramatic evidence that it would actually work. This work was published in 1998 and the paper - well worth reading - is online. To my continued astonishment it manages to avoid all mention of the pioneering series of papers published by the Rotterdam group that demonstrated that ERT was a runner. I guess this was a sign that things were about to become competitive (the paper acknowledges funding by Synpac). Aside from the fact that the reviewers should have picked the omission up, it was just plain bad form.
However, just like a TV drama, there were twists and turns ahead that we could not conceive of. And speaking of TV, do I get a prize for an article involving Slough that does not mention The Office?
A report from the Slough Observer! Photo shows Mayor Minhas, Me, Elaine & Euan, Arnold Reuser and Ann Philips. It also contains my embryonic daughter, Catriona who was born in December. We got the CVS all-clear on the drive down.
And the rival Sough Express was not to be outdone!
There were a series of remarkable presentations too. Arnold Reuser gave a talk on the latest developments in ERT and was helped in the following Q & A session by Gerben Moolhuizen.
That was obviously exciting. However, the following presentation by YT Chen was a real show-stopper. Yt presented his work involving Japanese quails, an unusual choice of experimental animal, explained by the fact that they have the bird equivalent of Pompe disease.
The affected birds were unable to move their wings, or to right themselves after being turned over. After 3 weeks treatment with enzyme produced in YT's lab (at Duke University USA) one of the birds was able to fly - and was only stopped after it hit a light stand! Analysis showed that their heart and liver had returned to normal and that their skeletal muscle, while still containing some glycogen, showed obvious signs of improvement - and, more to the point, fairly spectacular evidence of recovered function!
However, just like a TV drama, there were twists and turns ahead that we could not conceive of. And speaking of TV, do I get a prize for an article involving Slough that does not mention The Office?
Pharming
Pharming were - and are - a fantastic company. They were pioneers in the field of transgenic animals. Relatively small, young and adventurous. That's why they were willing to take a risk on a product for a disease that no-one had heard of. I am of the belief that without Pharming the development of ERT for Pompe disease would have been much delayed. Certainly, Genzyme had not shown any interest when I had written to them regarding the Rotterdam work.
Over the years they were involved with the Pompe project, I always got the impression that this was more than just a job - they believed in this project. That high level of motivation made for good relations with the patient community and undoubtedly helped progress. They were the right company, with the right product at the right time. And the fact that they were nearly destroyed by later corporate chicanery does not detract from that one bit. I hope that all those from Pharming look back on their involvement with the patient community with pride. We owe them our thanks.
No-one exemplified the Pharming commitment to the Pompe project better than Gerben Moolhuizen, the Project Director. Gerben got in touch in early 1997, to bring me up to date with the project. That established a relationship between the AGSD-UK and Pharming based on openess and trust. They knew that confidential and commercially sensitive information could be shared without it going any further.
Pharming were taking a novel and potentially controversial approach. They had genetically engineered animals by adding the human alpha-glucosidase gene to them, along with a marker that meant that the resulting human enzyme was expressed in the animals' milk. This cleverly did away with the need for complex bioreactors, with all their special growth mediums, difficulties in keeping sterile. Just feed grass in and get alpha-glucosidase-rich milk out.
One problem though was that the animal Pharming were not producing the milk in cows, or even sheep or goats - but rabbits. At first this seems odd, not to say bizarre. However the reasoning was solid - the rapid generation time allowed production to be increased quickly due to the relatively short time taken for the animals to reach breeding (and milk producing) maturity. The downside was that it was going to take an awful lot of rabbits to produce the required volume of milk.
One question I often used to get asked was "But how do you milk a rabbit?" To which the obvious answer was "You sit on a very small stool." However the true - and only slightly less amusing answer - is that you buy a rabbit-milking machine. Apparently cheese made from rabbit milk is considered to be a delicacy in some quarters. Who knew?
As a postscript to the above, I once asked Gerben Moolhuizen what precautions were taken to preserve these very valuable rabbits, in the case of some catastrophic accident. he replied that I shouldn't worry because samples of semen from the genetically engineered rabbits were deep frozen so that, in such an event, the breeding line could be quickly restored. I mention that simply to point out that there are worse jobs than milking rabbits.
Over the years they were involved with the Pompe project, I always got the impression that this was more than just a job - they believed in this project. That high level of motivation made for good relations with the patient community and undoubtedly helped progress. They were the right company, with the right product at the right time. And the fact that they were nearly destroyed by later corporate chicanery does not detract from that one bit. I hope that all those from Pharming look back on their involvement with the patient community with pride. We owe them our thanks.
No-one exemplified the Pharming commitment to the Pompe project better than Gerben Moolhuizen, the Project Director. Gerben got in touch in early 1997, to bring me up to date with the project. That established a relationship between the AGSD-UK and Pharming based on openess and trust. They knew that confidential and commercially sensitive information could be shared without it going any further.
Pharming were taking a novel and potentially controversial approach. They had genetically engineered animals by adding the human alpha-glucosidase gene to them, along with a marker that meant that the resulting human enzyme was expressed in the animals' milk. This cleverly did away with the need for complex bioreactors, with all their special growth mediums, difficulties in keeping sterile. Just feed grass in and get alpha-glucosidase-rich milk out.
One problem though was that the animal Pharming were not producing the milk in cows, or even sheep or goats - but rabbits. At first this seems odd, not to say bizarre. However the reasoning was solid - the rapid generation time allowed production to be increased quickly due to the relatively short time taken for the animals to reach breeding (and milk producing) maturity. The downside was that it was going to take an awful lot of rabbits to produce the required volume of milk.
One question I often used to get asked was "But how do you milk a rabbit?" To which the obvious answer was "You sit on a very small stool." However the true - and only slightly less amusing answer - is that you buy a rabbit-milking machine. Apparently cheese made from rabbit milk is considered to be a delicacy in some quarters. Who knew?
As a postscript to the above, I once asked Gerben Moolhuizen what precautions were taken to preserve these very valuable rabbits, in the case of some catastrophic accident. he replied that I shouldn't worry because samples of semen from the genetically engineered rabbits were deep frozen so that, in such an event, the breeding line could be quickly restored. I mention that simply to point out that there are worse jobs than milking rabbits.
Wednesday, 2 December 2009
The AGSD-UK
As well as ever-expanding email contacts, I was also involved with the flesh and blood GSD community in the form of the AGSD-UK.
I was a member of the AGSD-UK Executive and I'll try and give some small flavour of that here. When I joined in 1993, the AGSD-UK was already an organisation in transition. From meeting in scout huts, it was growing in size and professionalism, with all the accompanying strains. The 1994 conference, organised by Henry and Janet Thomson, was the first which had gathered people in the same hotel overnight, with the conference proper in a nearby hospital. My wife and I took that to its logical conclusion in 1996, by organising the conference in Edinburgh and making it entirely hotel based - and so it has been ever since.
The AGSD-UK Executive used to meet in London, at the rather grand offices of a firm of solicitors, Winckworth and Pemberton, just round the corner from the Houses of Parliament. This was courtesy of the late Nick Owston who was a partner in the firm. Nick had Mcardles disease (GSD type 5) and represented those patients on the Executive. Nick was a real gentleman. He could have bought and sold the lot of us but you'd never have guessed - he was entirely unassuming. He was happy to host the AGSD-UK meetings and, on occasion, to provide top notch legal advice, all the while quietly encouraging things along from the sidelines. He also organised a robust international survey of Mcardles patients which remains the gold standard for information about that disease. It's a cliche, I know, but he really is much missed by everyone who knew him.
In my time, the husband and wife team of John and Sue Del Mar were chairman and treasurer respectively. Sue is charm personified and absolutely unflappable. She has always reminded me, as she will now be surprised to read, of Lady Penelope from Thunderbirds. I suspect that Sue will not find the comparison with a puppet to be a very flattering one. However, I can assure her that it is, as all men of a certain age will agree. John will be relieved to hear that he bears no resemblance to Lady Penelope's side-kick, Parker. John brought a business-like approach to the chairing of meetings and helped smooth things along, when they got sticky. As they did. Again, a successful businessman who cheerfully gave his free time to helping a small charity. John and Sue were two of the original founders of the AGSD-UK and have a son, Hugo, who has type 1.
Another regular presence was Phil Lee, a doctor specialising in metabolic diseases at the Institute of Child Health in London. Phil gave a lot of his time to help the GSD, coming to conferences as well as exec meetings and providing some essential medical backbone and advice. He had enormous enthusiasm and, as well as research, was something of a pioneer in establishing clincis for adults with metabolic diseases. Again, a remarkable talent attracted to this small charity, helping it punch above its weight and a good friend to the GSD community. I was sorry to hear that he has recently retired through ill-health and I wish him well.
Which brings me to Ann Phillips, El Presidente. I love Ann dearly, and the fact that the range of talented people described above gave up so much time to such a small charity is a testament to her energy and commitment. She was (still is) a force of nature that the AGSD-UK just gravitated around. All that talent was just drawn in by centrifugal force. But, goodness me, it could be hard work. Ann could be very single-minded and also had an understandable attachment to the organisation she had co-founded. This made for interesting meetings, which could ocasionally get heated. Sometimes she and I argued - she would occasionally try to spend the Pompe fund on other things, for example. However, Ann has a heart as big as the Atlantic that separates her US birthplace from the UK. You could have a stand-up row with her one minute and it was done and forgotten the next. The bottom line is that AGSD-UK simply wouldn't have existed without her and GSD patients in the UK and beyond will always be in her debt.
Ann co-founded the AGSD-UK because her youngest son Peter had GSD type 1. It is a real tragedy that Peter died in 2008, after 3 failed liver transplants. He was a fine young man, who, as well as contributing to the AGSD-UK in his own right, was a paediatric nurse, dedicated to helping others. The apple doesn't fall too far from the tree.
Postscript
The Pompe report stuck out like a sore thumb from the rest of the AGSD-UK business, simply because there was so much going on - research, clinical trials, conferences, meetings with companies and so on. I would give some rather breathless account of what was happening and one of Ann's foibles was to listen and then say "Kevin, that's great but, you know, you should always say 'AGSD-UK' and not 'AGSD' because that will confuse people." Which always seemed like a bit of a non-sequitur and classic Ann. Imagine my huge amusement then, when I'd started writing this blog, to receive an email from Allan Muir, my Pompe group successor, saying "Good blog Kevin - but please remember to say 'AGSD-UK' and not 'AGSD'" Well it amused me anyway. You had to be there, I guess.
I do miss those AGSD-UK Executive meetings. They were a good supportive bunch of people (apologies to those I haven't mentioned - I stuck to the core people who were there all the way through my time on it.) and I always came away from them with a spring in my step.
I was a member of the AGSD-UK Executive and I'll try and give some small flavour of that here. When I joined in 1993, the AGSD-UK was already an organisation in transition. From meeting in scout huts, it was growing in size and professionalism, with all the accompanying strains. The 1994 conference, organised by Henry and Janet Thomson, was the first which had gathered people in the same hotel overnight, with the conference proper in a nearby hospital. My wife and I took that to its logical conclusion in 1996, by organising the conference in Edinburgh and making it entirely hotel based - and so it has been ever since.
The AGSD-UK Executive used to meet in London, at the rather grand offices of a firm of solicitors, Winckworth and Pemberton, just round the corner from the Houses of Parliament. This was courtesy of the late Nick Owston who was a partner in the firm. Nick had Mcardles disease (GSD type 5) and represented those patients on the Executive. Nick was a real gentleman. He could have bought and sold the lot of us but you'd never have guessed - he was entirely unassuming. He was happy to host the AGSD-UK meetings and, on occasion, to provide top notch legal advice, all the while quietly encouraging things along from the sidelines. He also organised a robust international survey of Mcardles patients which remains the gold standard for information about that disease. It's a cliche, I know, but he really is much missed by everyone who knew him.
In my time, the husband and wife team of John and Sue Del Mar were chairman and treasurer respectively. Sue is charm personified and absolutely unflappable. She has always reminded me, as she will now be surprised to read, of Lady Penelope from Thunderbirds. I suspect that Sue will not find the comparison with a puppet to be a very flattering one. However, I can assure her that it is, as all men of a certain age will agree. John will be relieved to hear that he bears no resemblance to Lady Penelope's side-kick, Parker. John brought a business-like approach to the chairing of meetings and helped smooth things along, when they got sticky. As they did. Again, a successful businessman who cheerfully gave his free time to helping a small charity. John and Sue were two of the original founders of the AGSD-UK and have a son, Hugo, who has type 1.
Another regular presence was Phil Lee, a doctor specialising in metabolic diseases at the Institute of Child Health in London. Phil gave a lot of his time to help the GSD, coming to conferences as well as exec meetings and providing some essential medical backbone and advice. He had enormous enthusiasm and, as well as research, was something of a pioneer in establishing clincis for adults with metabolic diseases. Again, a remarkable talent attracted to this small charity, helping it punch above its weight and a good friend to the GSD community. I was sorry to hear that he has recently retired through ill-health and I wish him well.
Which brings me to Ann Phillips, El Presidente. I love Ann dearly, and the fact that the range of talented people described above gave up so much time to such a small charity is a testament to her energy and commitment. She was (still is) a force of nature that the AGSD-UK just gravitated around. All that talent was just drawn in by centrifugal force. But, goodness me, it could be hard work. Ann could be very single-minded and also had an understandable attachment to the organisation she had co-founded. This made for interesting meetings, which could ocasionally get heated. Sometimes she and I argued - she would occasionally try to spend the Pompe fund on other things, for example. However, Ann has a heart as big as the Atlantic that separates her US birthplace from the UK. You could have a stand-up row with her one minute and it was done and forgotten the next. The bottom line is that AGSD-UK simply wouldn't have existed without her and GSD patients in the UK and beyond will always be in her debt.
Ann co-founded the AGSD-UK because her youngest son Peter had GSD type 1. It is a real tragedy that Peter died in 2008, after 3 failed liver transplants. He was a fine young man, who, as well as contributing to the AGSD-UK in his own right, was a paediatric nurse, dedicated to helping others. The apple doesn't fall too far from the tree.
Postscript
The Pompe report stuck out like a sore thumb from the rest of the AGSD-UK business, simply because there was so much going on - research, clinical trials, conferences, meetings with companies and so on. I would give some rather breathless account of what was happening and one of Ann's foibles was to listen and then say "Kevin, that's great but, you know, you should always say 'AGSD-UK' and not 'AGSD' because that will confuse people." Which always seemed like a bit of a non-sequitur and classic Ann. Imagine my huge amusement then, when I'd started writing this blog, to receive an email from Allan Muir, my Pompe group successor, saying "Good blog Kevin - but please remember to say 'AGSD-UK' and not 'AGSD'" Well it amused me anyway. You had to be there, I guess.
I do miss those AGSD-UK Executive meetings. They were a good supportive bunch of people (apologies to those I haven't mentioned - I stuck to the core people who were there all the way through my time on it.) and I always came away from them with a spring in my step.
Tuesday, 1 December 2009
GSDNet
I have a huge file of emails, dating from 1995 or so onwards. Looking through 1996, I'm struck by the number of contacts from around the world, many of them nothing directly to do with Pompe disease but with genetic diseases in general. The internet was a much smaller place in those days!
Through hosting the AGSD-UK website, I was gradually amassing a number of glycogen storage disease contacts and I wanted to do something with them, to enable all these people to speak to each other. But what?
For some time the only place where patients could communicate on genetic diseases was an email mailing list called gendisease-j, run by a chap called Wayne Rosenfield. Gendisease-j (now called gaucherdisease) was ostensibly for diseases that have a greater predominance in the Jewish community, which included a number of lysosomal storage diseases. Importantly, this included Gaucher disease, which already had an enzyme replacement therapy. Although I am not Jewish and Pompe wasn't really within gendisease-j's remit, I was welcomed and made to feel right at home in that community. A small but characteristic kindness on Wayne's part. That in turn led to contacts with the Gaucher Society in the UK, which proved important. But I digress.
Having seen at first hand the community that Wayne had created, I thought it would be good to try and create something similar for the glycogen storage diseases. And welcoming as the gendisease-j community were, it's one thing to be a guest and another to invite all your friends and family to stay too. So I asked Wayne how to go about setting up a mailing list and he kindly took the time to put me in contact with someone who could help at St Johns University (which at that time hosted a number of medical lists) and then talked me through the business of setting up and running a mailing list. Wayne has been a source of help and advice over the years since - indeed, I have shamelessly plagiarised many of his ideas. So can I just take this opportunity to say - Wayne, thanks for everything.
I had an accomplice in setting up the new mailing list - John Bird of the AGSD-US. John - inexplicably - didn't think my initial title of Gendisease-gsd was a good one and so a return to the drawing board came up with GSDNet - which was duly launched in June 1996. I thought at the time that it would be great if we could get 50 people to join and hoped that we would have enough to talk to each other about. I needn't have worried. GSDNet quickly grew in size and also, I think, in depth. People from all over the world found that they were no longer isolated but part of a community. A community that has shared successes and supported each other through life's ebbs. It has also provided those affected by GSD with a voice at crucial junctures. I can't better the description from the Australian Pompe Association website:
Along the way, we added Ruth Speary and then Bet Cook as co-owners. Truth be told, it's Bet who does most of the actual work these days. Take a bow, Bet.
Today GSDNet has over 500 members, from all parts of the world and is the leading online resource for glycogen storage diseases. It works so well because it is more than the sum of its parts - and that is down to every one of its members. Well done all.
Through hosting the AGSD-UK website, I was gradually amassing a number of glycogen storage disease contacts and I wanted to do something with them, to enable all these people to speak to each other. But what?
For some time the only place where patients could communicate on genetic diseases was an email mailing list called gendisease-j, run by a chap called Wayne Rosenfield. Gendisease-j (now called gaucherdisease) was ostensibly for diseases that have a greater predominance in the Jewish community, which included a number of lysosomal storage diseases. Importantly, this included Gaucher disease, which already had an enzyme replacement therapy. Although I am not Jewish and Pompe wasn't really within gendisease-j's remit, I was welcomed and made to feel right at home in that community. A small but characteristic kindness on Wayne's part. That in turn led to contacts with the Gaucher Society in the UK, which proved important. But I digress.
Having seen at first hand the community that Wayne had created, I thought it would be good to try and create something similar for the glycogen storage diseases. And welcoming as the gendisease-j community were, it's one thing to be a guest and another to invite all your friends and family to stay too. So I asked Wayne how to go about setting up a mailing list and he kindly took the time to put me in contact with someone who could help at St Johns University (which at that time hosted a number of medical lists) and then talked me through the business of setting up and running a mailing list. Wayne has been a source of help and advice over the years since - indeed, I have shamelessly plagiarised many of his ideas. So can I just take this opportunity to say - Wayne, thanks for everything.
I had an accomplice in setting up the new mailing list - John Bird of the AGSD-US. John - inexplicably - didn't think my initial title of Gendisease-gsd was a good one and so a return to the drawing board came up with GSDNet - which was duly launched in June 1996. I thought at the time that it would be great if we could get 50 people to join and hoped that we would have enough to talk to each other about. I needn't have worried. GSDNet quickly grew in size and also, I think, in depth. People from all over the world found that they were no longer isolated but part of a community. A community that has shared successes and supported each other through life's ebbs. It has also provided those affected by GSD with a voice at crucial junctures. I can't better the description from the Australian Pompe Association website:
GSDNet is an Internet Mailing List for patients, their families and friends, and professionals.
It is a mailing list for all Glycogen Storage Diseases, including Pompe’s Disease, and here you will meet a great bunch of people.
You can email with other Pompe’s patients world-wide. And if you feel alone and isolated with this disease, or if you want to talk with someone who will understand just what you are going through, if you want to ask questions or you just want to receive the latest news, then this is the right place for you.
You can receive email for all Glycogen Storage Diseases or you can set your particulars so that you will only receive mail pertaining to Pompe’s Disease.
And the good thing is - It’s Free!!
Along the way, we added Ruth Speary and then Bet Cook as co-owners. Truth be told, it's Bet who does most of the actual work these days. Take a bow, Bet.
Today GSDNet has over 500 members, from all parts of the world and is the leading online resource for glycogen storage diseases. It works so well because it is more than the sum of its parts - and that is down to every one of its members. Well done all.
Sunday, 29 November 2009
AGSD-UK helps fund Rotterdam group
The UK Pompe patients, organised within the AGSD-UK, had a clear goal. We wanted to raise funds and raise awareness, in order to help the Rotterdam group take their work on ERT forward.
In 1996, there was an opportunity to do exactly that.
The problem for the Dutch group (I am putting words into their mouths here, for which I apologise) was to find a way to make the jump from their ground-breaking experiments that demonstrated that ERT could work in principle, to clinical trials. The funding required for that (£ millions) seemed like an insurmountable problem, however they took the sensible approach of taking one small step at a time. For example, a collaboration with John Hopwood's lab in Australia had resulted in the development of cells which produced alpha-glucosidase (complete with the critical sugar residues attached) and which were suitable for growing in a production vessel.
The strategy was therefore to use the Hopwood cell line to produce enough alpha-glucosidase to treat one or two patients and hope that a pharmaceutical company would then take it up. This was, to say the least, an approach fraught with uncertainty. However it is also true to say that there was no alternative.
To produce the enzyme, it was proposed to use a new company started by a former student (Martin van der Vliet) of Arnold Reuser's, called Biocell technology, who would build a small-scale fermenter. However this work, while being done at a bargain rate, still needed funding- and, despite applications to grant-awarding bodies and biotechnology companies, none was forthcoming. That was where the AGSD-UK were able to step in and fund the building of the fermenter via a grant of £10,000. Here's a photo of it below (that's the old AGSD-UK logo in the corner):
This was a great day for the UK Pompe patients - at last we were taking an active part in shaping our own destiny. At the same time, the AMDA were funding similar work at Y T Chen's lab in the US (along with other projects).
I think that the AMDA had also offered to fund the Rotterdam work, however Arnold Reuser and Ans van der Ploeg opted to receive the money from the AGSD-UK instead, a route that involved them in a bit more hoop-jumping. Why? I don't know for sure but here are my guesses. Firstly, they knew how much it would mean to us to do it. Secondly, it always makes sense to keep a diverse range of funding options open - and they knew that the AMDA route would still be open to them in the future. Thirdly - and this is a complete guess on my part - Arnold had a shrewd idea that by allowing us to become a funder, it would give us a seat in future discussions on the development of ERT.
£10,000 is, of course, in the grand scheme of things a small amount (though it represented a lot of hard work and generosity by many people). However, I believe that it had an effect out of all proportion to the amount. Again, I am departing into the realm of conjecture here - what follows represents my opinion only and I am not going to present any evidence to back it up:-)
The reactor was indeed used to produce enzyme that was used in experimental work. However it also demonstrated to Erasmus University (and Sophia Children's Hospital) that the Pompe group were capable of raising funds from overseas to further their work. I think that would have helped to boost their profile. Most important of all, the Rotterdam group had been in discussions with a biotech company called Pharming, regarding the production of alpha-glucosidase in the milk of transgenic animals. These discussions had been going on for a while and were inconclusive. However the advent of a new funding source (conveniently omitting that it was a small charity with limited resources) may have helped to push Pharming into a decision to commit to the project. It's a great theory - but I have absolutely no idea if it's true!
Soon after, Pharming did indeed commit to the Pompe project. And that decision was the key to making things happen.
In 1996, there was an opportunity to do exactly that.
The problem for the Dutch group (I am putting words into their mouths here, for which I apologise) was to find a way to make the jump from their ground-breaking experiments that demonstrated that ERT could work in principle, to clinical trials. The funding required for that (£ millions) seemed like an insurmountable problem, however they took the sensible approach of taking one small step at a time. For example, a collaboration with John Hopwood's lab in Australia had resulted in the development of cells which produced alpha-glucosidase (complete with the critical sugar residues attached) and which were suitable for growing in a production vessel.
The strategy was therefore to use the Hopwood cell line to produce enough alpha-glucosidase to treat one or two patients and hope that a pharmaceutical company would then take it up. This was, to say the least, an approach fraught with uncertainty. However it is also true to say that there was no alternative.
To produce the enzyme, it was proposed to use a new company started by a former student (Martin van der Vliet) of Arnold Reuser's, called Biocell technology, who would build a small-scale fermenter. However this work, while being done at a bargain rate, still needed funding- and, despite applications to grant-awarding bodies and biotechnology companies, none was forthcoming. That was where the AGSD-UK were able to step in and fund the building of the fermenter via a grant of £10,000. Here's a photo of it below (that's the old AGSD-UK logo in the corner):
This was a great day for the UK Pompe patients - at last we were taking an active part in shaping our own destiny. At the same time, the AMDA were funding similar work at Y T Chen's lab in the US (along with other projects).
I think that the AMDA had also offered to fund the Rotterdam work, however Arnold Reuser and Ans van der Ploeg opted to receive the money from the AGSD-UK instead, a route that involved them in a bit more hoop-jumping. Why? I don't know for sure but here are my guesses. Firstly, they knew how much it would mean to us to do it. Secondly, it always makes sense to keep a diverse range of funding options open - and they knew that the AMDA route would still be open to them in the future. Thirdly - and this is a complete guess on my part - Arnold had a shrewd idea that by allowing us to become a funder, it would give us a seat in future discussions on the development of ERT.
£10,000 is, of course, in the grand scheme of things a small amount (though it represented a lot of hard work and generosity by many people). However, I believe that it had an effect out of all proportion to the amount. Again, I am departing into the realm of conjecture here - what follows represents my opinion only and I am not going to present any evidence to back it up:-)
The reactor was indeed used to produce enzyme that was used in experimental work. However it also demonstrated to Erasmus University (and Sophia Children's Hospital) that the Pompe group were capable of raising funds from overseas to further their work. I think that would have helped to boost their profile. Most important of all, the Rotterdam group had been in discussions with a biotech company called Pharming, regarding the production of alpha-glucosidase in the milk of transgenic animals. These discussions had been going on for a while and were inconclusive. However the advent of a new funding source (conveniently omitting that it was a small charity with limited resources) may have helped to push Pharming into a decision to commit to the project. It's a great theory - but I have absolutely no idea if it's true!
Soon after, Pharming did indeed commit to the Pompe project. And that decision was the key to making things happen.
1996
A quick summary of where we were at in 1996.
In retrospect, this was a pivotal year though it didn't seem so at the time. The patient group in the UK was growing slowly. The Pompe's Bulletin newletter was circulated to any patients, doctors and scientists that we could think of. The patient groups in different countries began to reach out to each other via the internet. Another common link was Arnold Reuser's group on Rotterdam - their willingness to engage with the growing patient community was crucial to its development. They struck a careful balance between their compassion and their professionalism. There was a growing sense of beginning to come together for a common purpose. Little did we know that things were about to kick off in a quite astonishing way. But that's for 1997:-) First a couple of articles on 1996.
In retrospect, this was a pivotal year though it didn't seem so at the time. The patient group in the UK was growing slowly. The Pompe's Bulletin newletter was circulated to any patients, doctors and scientists that we could think of. The patient groups in different countries began to reach out to each other via the internet. Another common link was Arnold Reuser's group on Rotterdam - their willingness to engage with the growing patient community was crucial to its development. They struck a careful balance between their compassion and their professionalism. There was a growing sense of beginning to come together for a common purpose. Little did we know that things were about to kick off in a quite astonishing way. But that's for 1997:-) First a couple of articles on 1996.
Saturday, 14 November 2009
House improvements
I have tried to make this a roughly chronological account but I'm going to go off piste here because I can't give a good portrait of Randall and Marylyn without looking ahead.
In front of me is my first written communication from the Houses. Dated 29 August, 1995, it expresses sympathy for our loss of Calum, introduces Randall, Marylyn and their daughter Tiffany (then just a 12-year-old slip of a girl) who has Pompe (they have two other children, who do not), shares their conclusions so far and a sheaf of information on diet, including a paper by Pompe patient Donald Ewers. In hindsight it has all the hallmarks that mark out the Houses: compassion for others, sharp analysis and - above all - a drive to translate those things into action. It's a bit of a cliché but I found a lot of the American pioneer spirit in the Houses.
We talked on the phone and exchanged emails and gradually built up a relationship. My dealings were mainly with Randall, whose no-nonsense approach impressed me. We were fairly guarded with each other at first, as we worked out each other's agendas. It's probably true to say that I respected Randall before I liked him - though I came to like him a great deal. He is straight-talking - not given to exaggeration or soft-soaping. I found that if he said something, he meant it and if he said he would do something, he did it. I quickly realised that the Houses' resources were in a different league and that the most useful thing I could do was to be as open as possible and hope that it was reciprocated (it was).
Randall's words to me were along the lines of "We are not super-wealthy but we do have some means. We would like to use that means to find a treatment for this disease." Little did I realise then how much they would do. I also didn't fully appreciate at the time what those words meant. The Houses owned (still do, I think) a manufacturing business that they had devoted years to building up. That "some means" came from hard work and toil. I think it was, to a significant extent, their life's work up to that point. And yet they unhesitatingly put it at the service of finding a treatment for Pompe disease. In my view, their contribution to the development of a treatment for Pompe disease is as much their life's work as building their successful business.
I think I suggested that to have maximum effect they should found a patient organisation (the AGSD-US was, for whatever reason, less amenable to a devolved Pompe group than the UK version) , rather than act as individuals, and also have a scientific advisory board, to ensure that their money was spent wisely. We were both agreed that enzyme replacement therapy was the way to go. I don't know whether I had any actual influence, however Randall and Marylyn founded the Acid Maltase Deficiency Association (AMDA) as a patient organisation. They used that as their base to do some remarkable things.
Firstly, they built the AMDA as a source of advice and information for hundreds of people affected by Pompe disease. Secondly, they did something that had never been done before. They gathered together, at their own personal expense, Pompe experts from all over the globe and hosted a conference for them in San Antonio, Texas. This was on March 21-22, 1996. The talks read like a who's who of the Pompe world. It was followed by a second, even bigger, conference on June 22-23, 1997.
Organising these conferences was an imaginative and far-sighted act. As important, I think, as the funding that the Houses put into research (again, a significant amount - nearly $5 million to date, according to the AMDA website). They were obviously scientific conferences, not patient ones, however the Houses were kind enough to send me video recordings of each conference, which allowed me to keep right up to date with what was happening. A characteristic piece of generosity on their part.
Looking at the 1996 programme now, I am amused to note that the session started at 7.00 am with breakfast and registration. That's approximately 2.5 hours earlier than most scientists are used to, so I guess Randall and Marylyn were putting their own work ethic stamp on proceedings from the start (1997 had a more leisurely 7.30 am start). The programme was designed by one Tiffany Laurel House, who now heads up the AMDA.
In the founding of the AMDA and the gathering of US patients together, and bringing together scientists, Randall and Marylyn were playing the major role in creating a worldwide Pompe community. In extending those connections to industry (I'm really getting ahead of myself now) they helped found a new model in the development of treatments for rare diseases, one in which patients, researchers, doctors and companies interact. The development of ERT for Pompe was possibly the first instance where an informed patient community said to industry, in effect, "We are your future customers, this is our condition and this is the treatment we would like you to develop." But more of that later.
For now, it's enough to say that Randall and Marylyn changed the game. In a very real sense, they made ERT happen. They made it happen while being part of an international community. And they made it happen not just for Tiffany but for all Pompe patients.
Postscript
I don't think I actually met Randall until 1997, at the AGSD-UK's annual conference. Here's my earliest memory of him. We had introduced ourselves and I noted that he was wearing a formal business suit, unlike my scruffy self. I was fussing about trying to make some sense of the organisation of the Pompe session out of the customary AGSD-UK chaos. There was a group of parents who had found some space on the floor in order to feed/change their young children. Next time I turned around, Randall had hunkered down on the floor, amongst the crumbs, in his business suit, in order to talk with them. That's my abiding image of Randall House. Sorry, I can't tell you what brand of suit it was - or what kind of watch he was wearing.
In front of me is my first written communication from the Houses. Dated 29 August, 1995, it expresses sympathy for our loss of Calum, introduces Randall, Marylyn and their daughter Tiffany (then just a 12-year-old slip of a girl) who has Pompe (they have two other children, who do not), shares their conclusions so far and a sheaf of information on diet, including a paper by Pompe patient Donald Ewers. In hindsight it has all the hallmarks that mark out the Houses: compassion for others, sharp analysis and - above all - a drive to translate those things into action. It's a bit of a cliché but I found a lot of the American pioneer spirit in the Houses.
We talked on the phone and exchanged emails and gradually built up a relationship. My dealings were mainly with Randall, whose no-nonsense approach impressed me. We were fairly guarded with each other at first, as we worked out each other's agendas. It's probably true to say that I respected Randall before I liked him - though I came to like him a great deal. He is straight-talking - not given to exaggeration or soft-soaping. I found that if he said something, he meant it and if he said he would do something, he did it. I quickly realised that the Houses' resources were in a different league and that the most useful thing I could do was to be as open as possible and hope that it was reciprocated (it was).
Randall's words to me were along the lines of "We are not super-wealthy but we do have some means. We would like to use that means to find a treatment for this disease." Little did I realise then how much they would do. I also didn't fully appreciate at the time what those words meant. The Houses owned (still do, I think) a manufacturing business that they had devoted years to building up. That "some means" came from hard work and toil. I think it was, to a significant extent, their life's work up to that point. And yet they unhesitatingly put it at the service of finding a treatment for Pompe disease. In my view, their contribution to the development of a treatment for Pompe disease is as much their life's work as building their successful business.
I think I suggested that to have maximum effect they should found a patient organisation (the AGSD-US was, for whatever reason, less amenable to a devolved Pompe group than the UK version) , rather than act as individuals, and also have a scientific advisory board, to ensure that their money was spent wisely. We were both agreed that enzyme replacement therapy was the way to go. I don't know whether I had any actual influence, however Randall and Marylyn founded the Acid Maltase Deficiency Association (AMDA) as a patient organisation. They used that as their base to do some remarkable things.
Firstly, they built the AMDA as a source of advice and information for hundreds of people affected by Pompe disease. Secondly, they did something that had never been done before. They gathered together, at their own personal expense, Pompe experts from all over the globe and hosted a conference for them in San Antonio, Texas. This was on March 21-22, 1996. The talks read like a who's who of the Pompe world. It was followed by a second, even bigger, conference on June 22-23, 1997.
Organising these conferences was an imaginative and far-sighted act. As important, I think, as the funding that the Houses put into research (again, a significant amount - nearly $5 million to date, according to the AMDA website). They were obviously scientific conferences, not patient ones, however the Houses were kind enough to send me video recordings of each conference, which allowed me to keep right up to date with what was happening. A characteristic piece of generosity on their part.
Looking at the 1996 programme now, I am amused to note that the session started at 7.00 am with breakfast and registration. That's approximately 2.5 hours earlier than most scientists are used to, so I guess Randall and Marylyn were putting their own work ethic stamp on proceedings from the start (1997 had a more leisurely 7.30 am start). The programme was designed by one Tiffany Laurel House, who now heads up the AMDA.
In the founding of the AMDA and the gathering of US patients together, and bringing together scientists, Randall and Marylyn were playing the major role in creating a worldwide Pompe community. In extending those connections to industry (I'm really getting ahead of myself now) they helped found a new model in the development of treatments for rare diseases, one in which patients, researchers, doctors and companies interact. The development of ERT for Pompe was possibly the first instance where an informed patient community said to industry, in effect, "We are your future customers, this is our condition and this is the treatment we would like you to develop." But more of that later.
For now, it's enough to say that Randall and Marylyn changed the game. In a very real sense, they made ERT happen. They made it happen while being part of an international community. And they made it happen not just for Tiffany but for all Pompe patients.
Postscript
I don't think I actually met Randall until 1997, at the AGSD-UK's annual conference. Here's my earliest memory of him. We had introduced ourselves and I noted that he was wearing a formal business suit, unlike my scruffy self. I was fussing about trying to make some sense of the organisation of the Pompe session out of the customary AGSD-UK chaos. There was a group of parents who had found some space on the floor in order to feed/change their young children. Next time I turned around, Randall had hunkered down on the floor, amongst the crumbs, in his business suit, in order to talk with them. That's my abiding image of Randall House. Sorry, I can't tell you what brand of suit it was - or what kind of watch he was wearing.
Making connections
The UK group was definitely stirring and I had a growing mailing list that I could send paper newsletters to. However I realised that there were probably patient groups and individuals in other countries going through exactly the same process - but how could I contact them?* The answer seems simple now - just use Google, d'oh! Unfortunately, in 1995 Google was yet to be invented. I had internet access at work though and was keen on the idea of using a website as a sort of shop window.
A bit of history/nostalgia. My first web browser was something called Lynx which was entirely text-based. I then started using something called Mosaic which had the startling innovation of allowing you to see pictures and text. I got a hold of it by email - you got sent the code for it in chunks and had to manually piece them together to make a functioning piece of software. Happy days. But I digress.
I put together a rudimentary website for the AGSD-UK and included the full text of my Pompe patients' guide. A friend at work kindly hosted on his webspace (cheers, David). But how could people find it? I emailed it around to anyone I could think of but there were no search engines as such. However a couple of students at Stanford University had used their university account to set up a sort of index for interesting websites, so I listed it there. They had called their site Yahoo. It'll never catch on with a name like that, I thought.
Anyways, I gradually made contact with people from other countries - individuals from Germany and the US to begin with. Then I got a phone call from a guy in the USA that I'd never heard of but who had come to the same conclusions as me and was determined to do something about them. His name was Randall House and he, along with his wife Marylyn, changed everything.
*I realise on looking through my papers that the original list of names I was given by Ann Philips contained one non-UK contact - Helen Walker from Australia. I'm surprised by that and also to find that I've now been in touch with Helen for 15 years! More about the Ozzies later.
A bit of history/nostalgia. My first web browser was something called Lynx which was entirely text-based. I then started using something called Mosaic which had the startling innovation of allowing you to see pictures and text. I got a hold of it by email - you got sent the code for it in chunks and had to manually piece them together to make a functioning piece of software. Happy days. But I digress.
I put together a rudimentary website for the AGSD-UK and included the full text of my Pompe patients' guide. A friend at work kindly hosted on his webspace (cheers, David). But how could people find it? I emailed it around to anyone I could think of but there were no search engines as such. However a couple of students at Stanford University had used their university account to set up a sort of index for interesting websites, so I listed it there. They had called their site Yahoo. It'll never catch on with a name like that, I thought.
Anyways, I gradually made contact with people from other countries - individuals from Germany and the US to begin with. Then I got a phone call from a guy in the USA that I'd never heard of but who had come to the same conclusions as me and was determined to do something about them. His name was Randall House and he, along with his wife Marylyn, changed everything.
*I realise on looking through my papers that the original list of names I was given by Ann Philips contained one non-UK contact - Helen Walker from Australia. I'm surprised by that and also to find that I've now been in touch with Helen for 15 years! More about the Ozzies later.
Tuesday, 6 October 2009
Ans van der Ploeg's visit to the AGSD-UK conference
As mentioned in an earlier post Dr Ans van der Ploeg had agreed to speak at the 1995 AGSD UK conference, which was held in Birmingham on 28 May.
This was a very exciting prospect. For one thing, it would give the other Pompe families the opportunity to see that the Dutch team were not a figment of my imagination. The impact of a real person standing in front them talking about her promising research was not to be under-estimated. It would also mark something of a departure of the AGSD-UK, with a main talk at the conference being given over to Pompe disease, rather than one of the liver-based GSDs.
In short, I was anxious for it to go well. So when Hugo Del Mar, son of AGSD-UK co-founder Sue Del Mar, offered to pick up Dr van der Ploeg from the airport in his new two-seater sports car, I was delighted. "That will impress her!", I thought. I reflected on this example of my innate shallowness later, as I watched a fairly heavily pregnant Ans van der Ploeg extricate herself from the tiny sports car...
Ans van der Ploeg (yes, the one on the right) receiving an award for her pioneering work on Pompe disease.
The talk itself was excellent and well-received. It strengthened the resolve of the Pompe group to do something to support the work of the Rotterdam team and fund-raising began in earnest, though there was, at that point, nothing specific to support. Nevertheless, from that time on, we had a real goal.
Dr van der Ploeg was, needless to say, charm itself and dealt with her and her unborn child being squeezed into a sports car with her customary sang-froid. Many people (most, even) would have found pregnancy a more than adequate reason to cancel the talk. However - and this is typical of the whole Rotterdam team - having made a commitment to patients, she did not want to disappoint, regardless of the personal inconvenience.
Ans van der Ploeg is blessed with cleverness, good looks and a list of achievements that includes - aside from the minor matter of developing a treatment for Pompe disease - such things as national cross-country skating.
Normally of course, such a super-abundance of talents in one individual would draw the disapproval of all right-thinking people, given that so many of us have to get by with none at all. However, like everyone else, I am prepared to make an exception in Ans' case, as she has put her considerable abilities towards the service of others - and with such good effect.
This was a very exciting prospect. For one thing, it would give the other Pompe families the opportunity to see that the Dutch team were not a figment of my imagination. The impact of a real person standing in front them talking about her promising research was not to be under-estimated. It would also mark something of a departure of the AGSD-UK, with a main talk at the conference being given over to Pompe disease, rather than one of the liver-based GSDs.
In short, I was anxious for it to go well. So when Hugo Del Mar, son of AGSD-UK co-founder Sue Del Mar, offered to pick up Dr van der Ploeg from the airport in his new two-seater sports car, I was delighted. "That will impress her!", I thought. I reflected on this example of my innate shallowness later, as I watched a fairly heavily pregnant Ans van der Ploeg extricate herself from the tiny sports car...
Ans van der Ploeg (yes, the one on the right) receiving an award for her pioneering work on Pompe disease.The talk itself was excellent and well-received. It strengthened the resolve of the Pompe group to do something to support the work of the Rotterdam team and fund-raising began in earnest, though there was, at that point, nothing specific to support. Nevertheless, from that time on, we had a real goal.
Dr van der Ploeg was, needless to say, charm itself and dealt with her and her unborn child being squeezed into a sports car with her customary sang-froid. Many people (most, even) would have found pregnancy a more than adequate reason to cancel the talk. However - and this is typical of the whole Rotterdam team - having made a commitment to patients, she did not want to disappoint, regardless of the personal inconvenience.
Ans van der Ploeg is blessed with cleverness, good looks and a list of achievements that includes - aside from the minor matter of developing a treatment for Pompe disease - such things as national cross-country skating.
Normally of course, such a super-abundance of talents in one individual would draw the disapproval of all right-thinking people, given that so many of us have to get by with none at all. However, like everyone else, I am prepared to make an exception in Ans' case, as she has put her considerable abilities towards the service of others - and with such good effect.
The Hal Brodhurst Trust
The Hal Brodhurst Trust has an honourable corner of the Pompe story that deserves to be remembered.
Hal was the son of Robin and Desiree Brodhurst and suffered from infantile Pompe disease. When he was 6 months old, Hal had a radical treatment, a combined heart and bone marrow transplant, carried out in July 1993. The surgeon was the heart transplant pioneer, Sir Magdi Yacoub. Sadly, the treatment was not effective and Hal died four months later.
His parents established the Hal Brodhurst Trust in July 1994, in order to help fund research into Pompe disease. The aims of the Trust were:
Something that particularly sticks in my mind is that Sir Magdi said that his research strategy would be to sequence the Pompe mutations, find out what had gone wrong and then find a way of making the mutated enzymes work again. I was astonished by this because it was vanishingly unlikely to work (I still do think that, regardless of the fact that an analogous approach is being pursued by Amicus Therapeutics) . Being a great man in one field is no guarantee of being right in another one. But I digress.
The team at Harefield, led by Ann Child of the Institute of Child Health in London, looked at Pompe tissue samples from across the UK and carried out DNA sequencing. The work was published in the journal Human Mutation in 1998. The paper, by Clare Beesley, described some novel mutations causing Pompe disease (including the one I carry, if I remember rightly). After that, the Trust faded from view and, as far as I know, no longer exists.
Partly, this was a reflection of the limitations of charities dedicated to one child. With the best will in the world, by their very nature they find it difficult to draw the wider support needed for the longer haul. This reinforced my view that the AGSD-UK route was the right one for whatever contribution I was able to make. It also brought home to me the importance of a Scientific Advisory Board to give broad-based specialist advice.
However, and most importantly, the Hal Brodhurst Trust had the considerable achievement of funding the first UK research into Pompe disease. An important milestone and a lasting memorial for Hal.
Hal was the son of Robin and Desiree Brodhurst and suffered from infantile Pompe disease. When he was 6 months old, Hal had a radical treatment, a combined heart and bone marrow transplant, carried out in July 1993. The surgeon was the heart transplant pioneer, Sir Magdi Yacoub. Sadly, the treatment was not effective and Hal died four months later.
His parents established the Hal Brodhurst Trust in July 1994, in order to help fund research into Pompe disease. The aims of the Trust were:
1. To advance education by the promotion of research into the causes and treatment of glycogen storage disorders with particular concern for type 2 Pompe's Disease on terms that the results of such research are published. 2. to relieve the sickness of people suffering from glycogen storage disorders with particular concern for type 2 Pompe's Disease and in particular and without limitation to promote the establishment of a unit dedicated to the treatment of glycogen storage disorder patients at a United Kingdom hospital.They raised funds which were put at the disposal of Magdi Yacoub, who established a small team at Harefield Hospital, near London. A Pompe Disease workshop was held there on 31 March 1995 and I attended on behalf of the AGSD-UK. The focus very much reflected Sir Magdi's own interests, with several talks on transplantation. Arnold Reuser also made a presentation. Robin and Desiree conducted themselves with their usual quiet dignity.
Something that particularly sticks in my mind is that Sir Magdi said that his research strategy would be to sequence the Pompe mutations, find out what had gone wrong and then find a way of making the mutated enzymes work again. I was astonished by this because it was vanishingly unlikely to work (I still do think that, regardless of the fact that an analogous approach is being pursued by Amicus Therapeutics) . Being a great man in one field is no guarantee of being right in another one. But I digress.
The team at Harefield, led by Ann Child of the Institute of Child Health in London, looked at Pompe tissue samples from across the UK and carried out DNA sequencing. The work was published in the journal Human Mutation in 1998. The paper, by Clare Beesley, described some novel mutations causing Pompe disease (including the one I carry, if I remember rightly). After that, the Trust faded from view and, as far as I know, no longer exists.
Partly, this was a reflection of the limitations of charities dedicated to one child. With the best will in the world, by their very nature they find it difficult to draw the wider support needed for the longer haul. This reinforced my view that the AGSD-UK route was the right one for whatever contribution I was able to make. It also brought home to me the importance of a Scientific Advisory Board to give broad-based specialist advice.
However, and most importantly, the Hal Brodhurst Trust had the considerable achievement of funding the first UK research into Pompe disease. An important milestone and a lasting memorial for Hal.
1995
Right, back to our trawl through the dusty archives. At the risk of eliminating all suspense, here are the things that happened: There was a UK Pompe meeting organised by the Hal Brodhurst Trust; Ans van der Ploeg came to the AGSD UK Conference; I started a website for the AGSD-UK, with Pompe information; and last but not least, I had my first contact with a US couple called Randall and Marylyn House. All important in their different ways. I'll do them as separate blogs over the next week or so.
Saturday, 26 September 2009
1994 continued
I'm really going through my big folder of emails, faxes, scribbled notes of phone calls etc. and trying to unpick what actually happened, so this narrative might seem a bit disjointed. Hopefully, others will now chip in with their own recollections to help fill in the gaps (hint).
For me personally, the big thing that happened with regard to this story was that I started building the Pompe Group in the AGSD-UK. There are several letters from people I met at the Newcastle conference, giving information, other contacts to follow up and so on. Email was not really widespread at this time, so most contact was by letter.
The main things I have are:
I persuaded the AGSD-UK to set up a Scientific Advisory Board, onto which Arnold Reuser and Ans van der Ploeg were invited, amongst others. This helped to provide some professional ballast for the AGSD-UK, while increasing its profile amongst medical and scientific professionals. You know, I still think that was a good move. Well done me;-)
The second thing was that the AGSD-UK set up a specific Pompe fund. This was to become a focus for fund-raising by the Pompe families (and still is).
The creation of the SAB was followed up by inviting Dr Ans van der Ploeg to speak at the next AGSD conference, to be held in Birmingham in May 1995. This invitation was in September 1994, so 8 months in advance. I'm flagging that up for a reason, so pay attention.
There was so much happening that I started a Pompe-specific newsletter - The Pompe's Bulletin - to use a a tool to keep people in touch and to spread the word. Initially 4 sides of A4 text, it has since become a high-quality, professional production. Of course, that only happened once I stopped having anything to do with it. You may see the start of a recurring theme here. Having said that, those newsletters, alongside the US equivalent produced by the AMDA (about to enter our story) are a pretty good historical record of events.
However, I can't let the round-up of 1994 pass without mention of the fact that we knew we were going to have another child and that our child would not have Pompe disease. chorionic villus sampling (CVS) is a technique that allows a sample of placenta to be tested for the presence of (in our case) alpha glucosidase. We had the test at 11 weeks. Not a great experience because you see the foetus on the screen, just like a normal ultrasound. We were trying not to look because, after all, we might have had to terminate the pregnancy. We knew that the sample was to be sent to Manchester and the test carried out there and were told to expect a result in a week or so. The hospital phoned the next day to give us the all clear. They must have had a courier waiting right there and then to take that sample to Manchester, where someone was waiting to - right there and then - start work on it.
The staff at the hospital were wonderful with us - though I don't think I've met anyone employed by the National Health Service who treats it as 'just a job'. They did everything they could to make things as easy for us as possible and treated us with great kindness. Hopefully we were able to show our gratitude at the time. However, there were a lot of people in that chain from Edinburgh to Manchester and back, who did well by us, and who we'll never know. People who are doing the same thing day in, day out for others. Our thanks to all of them from the very bottom of our hearts.
Euan was born in January 1995. The knowledge that we were having a healthy child made the last part of 1994 a very happy time for us.
So, the UK Pompe group was beginning to stir in 1994. This was only the start - the next year would see the start of an international network.
For me personally, the big thing that happened with regard to this story was that I started building the Pompe Group in the AGSD-UK. There are several letters from people I met at the Newcastle conference, giving information, other contacts to follow up and so on. Email was not really widespread at this time, so most contact was by letter.
The main things I have are:
I persuaded the AGSD-UK to set up a Scientific Advisory Board, onto which Arnold Reuser and Ans van der Ploeg were invited, amongst others. This helped to provide some professional ballast for the AGSD-UK, while increasing its profile amongst medical and scientific professionals. You know, I still think that was a good move. Well done me;-)
The second thing was that the AGSD-UK set up a specific Pompe fund. This was to become a focus for fund-raising by the Pompe families (and still is).
The creation of the SAB was followed up by inviting Dr Ans van der Ploeg to speak at the next AGSD conference, to be held in Birmingham in May 1995. This invitation was in September 1994, so 8 months in advance. I'm flagging that up for a reason, so pay attention.
There was so much happening that I started a Pompe-specific newsletter - The Pompe's Bulletin - to use a a tool to keep people in touch and to spread the word. Initially 4 sides of A4 text, it has since become a high-quality, professional production. Of course, that only happened once I stopped having anything to do with it. You may see the start of a recurring theme here. Having said that, those newsletters, alongside the US equivalent produced by the AMDA (about to enter our story) are a pretty good historical record of events.
However, I can't let the round-up of 1994 pass without mention of the fact that we knew we were going to have another child and that our child would not have Pompe disease. chorionic villus sampling (CVS) is a technique that allows a sample of placenta to be tested for the presence of (in our case) alpha glucosidase. We had the test at 11 weeks. Not a great experience because you see the foetus on the screen, just like a normal ultrasound. We were trying not to look because, after all, we might have had to terminate the pregnancy. We knew that the sample was to be sent to Manchester and the test carried out there and were told to expect a result in a week or so. The hospital phoned the next day to give us the all clear. They must have had a courier waiting right there and then to take that sample to Manchester, where someone was waiting to - right there and then - start work on it.
The staff at the hospital were wonderful with us - though I don't think I've met anyone employed by the National Health Service who treats it as 'just a job'. They did everything they could to make things as easy for us as possible and treated us with great kindness. Hopefully we were able to show our gratitude at the time. However, there were a lot of people in that chain from Edinburgh to Manchester and back, who did well by us, and who we'll never know. People who are doing the same thing day in, day out for others. Our thanks to all of them from the very bottom of our hearts.
Euan was born in January 1995. The knowledge that we were having a healthy child made the last part of 1994 a very happy time for us.
So, the UK Pompe group was beginning to stir in 1994. This was only the start - the next year would see the start of an international network.
Saturday, 19 September 2009
My first AGSD-UK conference
When Calum was diagnosed, one of the few things the hospital could do for us, was to give us a leaflet for an organisation called the Association for Glycogen Storage Disease (UK) (and also for the Research Trust for Metabolic Diseases in Children, now Climb) .
We called Ann Philips, the President, and she put us in touch with other families who had had a baby with Pompe's. It was an enormous comfort to speak to them - other people who understood what it was like to have lost a child to this rare disease. So we decided to go to their annual conference, which was being held in Newcastle on 29 May, 1994.
The organisers, Henry and Janet, couldn't have been kinder to us and they - and Ann - made us feel very welcome. Most of the conference dealt with the other types of glycogen storage disease - reasonably enough, as that reflected the membership. However, at some point, the Pompe families met together. I don't have a note of everyone who was there, however it certainly included the Harringtons (who had also lost a child to Pompe's and became good friends of ours) the Critchleys and Allan and Barbara Muir. Allan is the current UK Pompe supremo and (I'm jumping the narrative gun a bit here) has made a much better job of it than I ever did. If you are doing a job that really matters to you, then I can wish you no greater blessing than to have a successor who does it better. It's certainly been a source of great happiness for me - cheers, Allan!
But I digress. At that small gathering I spoke about the ERT research and we gave ourselves a target to raise funds to help it. I also found myself on the executive of the AGSD, representing the Pompe group.
Without really thinking about it, I'd made a decision that whatever efforts I made regarding Pompe disease, it would be as part of this group. In retrospect absolutely the right decision (how I wish they were all like that). The alternative was to start a new group specifically focused on Pompe disease. However being part of a larger group brought the advantages of critical mass (for example, tagging on to a group big enough to organise a proper conference) and opened me up to the constructive criticism of others. Both important things.
Of course, I didn't realise then quite how much of my life this was going to take up for the next 10 years or so... It is not an exaggeration to say that this was a meeting that changed my life.
The very next month, I was to have another important meeting.
We called Ann Philips, the President, and she put us in touch with other families who had had a baby with Pompe's. It was an enormous comfort to speak to them - other people who understood what it was like to have lost a child to this rare disease. So we decided to go to their annual conference, which was being held in Newcastle on 29 May, 1994.
The organisers, Henry and Janet, couldn't have been kinder to us and they - and Ann - made us feel very welcome. Most of the conference dealt with the other types of glycogen storage disease - reasonably enough, as that reflected the membership. However, at some point, the Pompe families met together. I don't have a note of everyone who was there, however it certainly included the Harringtons (who had also lost a child to Pompe's and became good friends of ours) the Critchleys and Allan and Barbara Muir. Allan is the current UK Pompe supremo and (I'm jumping the narrative gun a bit here) has made a much better job of it than I ever did. If you are doing a job that really matters to you, then I can wish you no greater blessing than to have a successor who does it better. It's certainly been a source of great happiness for me - cheers, Allan!
But I digress. At that small gathering I spoke about the ERT research and we gave ourselves a target to raise funds to help it. I also found myself on the executive of the AGSD, representing the Pompe group.
Without really thinking about it, I'd made a decision that whatever efforts I made regarding Pompe disease, it would be as part of this group. In retrospect absolutely the right decision (how I wish they were all like that). The alternative was to start a new group specifically focused on Pompe disease. However being part of a larger group brought the advantages of critical mass (for example, tagging on to a group big enough to organise a proper conference) and opened me up to the constructive criticism of others. Both important things.
Of course, I didn't realise then quite how much of my life this was going to take up for the next 10 years or so... It is not an exaggeration to say that this was a meeting that changed my life.
The very next month, I was to have another important meeting.
Friday, 24 April 2009
Calum
The morning glory that blooms for an hour, differs not at heart from the giant pine that lives for a thousand years.It was Friday 28 May, 1993 and one of the happiest days of my life. I was driving across the border from England into Scotland, to a new home in Edinburgh - the city I had always wanted to live in - and to my dream job, running my own molecular biology laboratory. Best of all, I had my family in the car with me - my wife Elaine and our two-month old baby son, Calum. Life was sweet. Yet within a few short months that sweetness turned to dust in my mouth.
Buddhist proverb
Everything was fine for a couple of months. I busied myself with settling in to my new job, while Elaine and Calum went house-hunting. Then Calum seemed to be getting a lot of colds and sniffles, which took longer and longer to go away. It never occurred to us for one moment that something could be seriously wrong. Even when, at six months old, Calum was hospitalised with pneumonia we didn't think it was anything other than a temporary blip. In hindsight we were incredibly naive - but what does anyone know with their first child?
An x-ray showed an enlarged heart and, even then, we didn't think anything other than "So he shouldn't play rough sports? Guess he'll just have to be geeky like his dad!" Unknown to us though, alarm bells were beginning to ring at the hospital and blood tests were taken "Just routine, nothing to be concerned about..." And we weren't concerned. We found a house (next to a park - and a school - perfect!) and started fixing it up prior to moving in.
Then we got the news that brought our world crashing down around our ears. On a follow-up hospital visit we were told that the blood tests showed Calum had something called Pompe disease which was a type of glycogen storage disease. It was untreatable and fatal; children with this disease did not usually live beyond their first birthday.
We just couldn't believe it. We thought that there must have been some terrible mistake. Our beautiful child, the light of our lives, going to die? How could such a thing be possible? And whoever heard of an untreatable disease in this day and age - those doctors really needed to keep up with what was happening in the world of medicine!
For the next two we weeks we frantically found out everything we could about Pompe disease and what little information there was available was not good. Everything confirmed what the hospital had told us; there was no hope. None. While we were still in shock, Calum declined quite rapidly and he went back into hospital. He died at the Sick Children's Hospital in Edinburgh, on 18 November 1993, just two weeks after we were given the diagnosis.
We used the Buddhist proverb from the beginning of this article as his epitaph. We both think of him every day and will always mourn the life that was lost. But we will always be grateful for the life that we had.
...
The hospital hadn't been able to help us with a treatment however they did one thing for us that was very helpful, both then and in the years ahead, and which was life-changing. They passed us details of two patient groups that helped families in our position. One was the Research Trust for Metabolic Diseases in Children (now known as Climb ), an umberella group for metabolic diseases, and the other was the Association for Glycogen Storage Disease UK, which dealt specifically with the glycogen storage diseases. Both organisations founded by remarkable women who responded to the illness of their own children by creating organisations that helped others. We will be forever indebted to Lesley Greene (Climb), Ann Philips (AGSD-UK) and the families they put us in touch with, for helping us through the darkest time of our lives. More of them later.
Following Calum's death we wanted to raise some funds for research into Pompe disease and I also had the idea that, as there was so little information available on Pompe disease, I would use my scientific background to write something aimed at parents. I felt that this was important because we had been desperate to understand what was happening to Calum and as I had watched Elaine (a bright person without a science background) struggle with concepts like genes, enzymes and lysosomes it was brought home to me what a privilege it is to be a scientist. It now gave me the opportunity to make a contribution that others were not in a position to make. I had thought that I would pull together what information there was and write up something for the AGSD. A sort of 'thank you' that would also be of a help to any future parents in our position. I didn't really see that there would be much that could be done beyond that.
The librarian at my work, Lynda, pulled a few strings to get me into the medical library at Edinbugh University and so I started carrying out a literature search on Pompe disease, helped by my cousin Aidan, who was a med student at the time. It was just the kind of mind-numbing, time-consuming task that I needed. In the far off days of 1993, younger readers may be surprised to learn, this was all done as a paper chase - looking up entries in publications like the citation index, then walking to shelves of actual hard-copy journals to look up the articles and see if they were of any interest. And if they were useful, you wrote the reference (by hand) on an index card and put it in a little desk file. Describing this to anyone under the age of 30 elicits a response that can only be compared with the old 'For mash get smash!' advert. But I digress.
And then something astonishing happened. Right then, in that library, amongst those dusty shelves of journals, I felt the sun come out. Because there, in my hands, was a paper that showed that Pompe disease was not the hopeless case that I had thought. A team of people in The Netherlands had been carrying out some ground-breaking research. They had worked out how Pompe disease could be treated and had designed some ingenious experiments to show that their idea could work.
I realised that I would be able to do more than just write an article for other parents to help them understand how their child was dying. I could write something explaining how this disease could be beaten. This was no longer a hopeless cause - it was a cause that could and must be won.
And the first step was to try to explain to other people just why what this Dutch group had done was so important. Which is something that I am going to do again in the next article.
Subscribe to:
Posts (Atom)
