Dr J C Pompe

Dr J C Pompe
Discoverer of Pompe disease

About this blog

What you can read here is the story of the development of enzyme replacement therapy (ERT), the first effective treatment for Pompe disease. It is an incredible story, rich with events, characters and science. Above all, it is the story of an international community of scientists, doctors, patients and companies, working together towards a common goal.

It is not a story that features in Geeta Anand's book, The Cure , or the film based on it, Extraordinary Measures despite the fact that they are ostensibly about the development of ERT for Pompe ( you can link straight to the relevant articles covering the events described in the book and film here, here and here).

This blog represents my small attempt to set the record straight and to give the story back to its rightful owners - the international Pompe community. It is written here in roughly chronological order i.e. you'll need to start at the bottom of the April 2009 archive page and work your way up.

It is also a personal account and, although I've tried to make it as objective as possible, there is an inevitable degree of subjectivity. For that reason I have included contributions from other members of the worldwide Pompe community and would be delighted to receive more. Feedback is also welcome.

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Sunday, 27 December 2009

IPA Founding Conference part 3

The conference was reported to the worldwide GSDNet audience by Gezinus Wolters. Here are his contemporary accounts (reprinted with permission):

Part 1 (posted Saturday 3 July, 1999)

As announced earlier I attended yesterday the first day of the IPA (International Pompe Association) in Naarden, Netherlands.

The conference is in a small hotel outside Naarden with conference facilities. Today the talks are mainly about the founding of the IPA itself and tomorrow (Sunday) Dr Ans van der Ploeg will report on the ongoing trials, which she leads. I will try to tell you about that too, later.

First, the atmosphere at the conference was very good, it had an exciting feeling.  No wonder, something is really happening.

A lot of faces of the names you only know from the GSDNET, all the icons of the Pompe-history (Dr. Loonen, Dr. Reuser, Kevin, the Houses, etc.). About 60 or 70 participants from all over the world (USA, UK, Netherlands, Belgium, France, Germany, Spain, Italy, India, Australia, Phillippines) and from all sectors: Industry, Universities, and Patient Organisations.

All in all there were ten presentations yesterday with a good overview of what is going on at the moment. I will not try to report on each introduction, but I will try to select the most interesting things.

There were three kinds of presentations: historical (Dr. Loonen and Dr. Reuser);reports on ongoing research (Prof Hopwood, Dr. Ausems, the Pharming people, Dr. Devlin (Synpac) and Dr. Amalfitano) and presentions from the patient (organisation) (Maryze, Kevin).

I'll skip the historic presentations, although they were both very interesting and inspiring. What is really amazing is, that this whole thing is still relatively new. Thirty years ago almost nobody knew anything about Pompe. And there is still a lot to be explained and investigated. Dr. Reuser and Dr. Looonen concluded with these things. What is really the differnce between infantile and adult forms? Why are different organisms affected? What exactly is the role of the missing enzyme (acid maltase)? We don't know.

Dr. Reuser emphasised the good relations between all Pompe researchers all over the world. Of course ther are different interests by the companies, but the academic researchers are cooperating and exchanging information very well. The presentaion of prof. Hopwood (Australia) was mainly about diagnosing. How to screen and diagnose Pompe early. Especially very, very important for the babies. For now a good indication can be gotten from a blood test (the standard Guthrie blood spots), which can be followed by a further diagnosis. So there is no viable blood test yet (but ther will be in the near future) but there are good indicative screening tests.

The presentation of Dr. Ausems (somebody called her Dr Awesome) had equally interesting conclusions. She investigated by several methods (genetic and from diagnoses) how much Pompe-patients there are. She concluded convincingly that there are a lot more Pompe patients than everybody thought earlier. Earlier number were that 1 in 100.000 (at least) people have Pompe.

Ausems concludes that here are 1 in 40.000 Pompe patients ! (about 1 in 100.000 infantile/juvenile and 1 in 57.000 adult).

So what does this mean? Is that good or bad? (I'm speaking for myself now, GW). Of course it is not good that there are much more Pompe-patients than we thought. And there is a higher chance that our children are effected. Maybe even there is a chance as high as 0,25 % (1 in 400) that a child of a Pompe-patient is effected.

But there is also a very beneficial positive effect. It may sound very cynical, but it means that there is a very much bigger market for the Pompe treatment than was estimated before and that it is much more interesting for companies to invest.  But these are all my conclusions, nothing to do with or said by Dr. Ausems, who just did a terrific job.

I come to the main dish now: the report on the ongoing research for the Pompe treatment.

Maybe you did not realise (I did not) but there is a three horse race going on to reach a admitted Pompe drug first. Or rather it is a two horse race with a third black horse as a very promising outsider.

Of course we know the first horse (leading by a length at the moment). A Dutch horse partly American-owned: the Therapy developed by Pharming and Genzyme.Pharming is producing the medicine, the enzyme alpha glucosidase (acid maltase), in the milk of transgenic rabbits. We passed animal tests (very positive results), phase 1 (safety tests on healthy people) and we are now in the middle of phase 2 (trials on 4 infantile and 2 juvenile patients). Dr. van der Ploeg will hopefully say more on Sunday, but according to reports now everything is going as well as can be expected. But it is too early for solid conclusions as yet. Pharming is expanding facilities at the moment, which means that they are building facilities for more rabbits and purification etc. All Pharming people reported that everything on the technical side is going well and that maybe (depending on the admission, the licensing, the approval) the medicine could be available mid-
or late 2000.

The second horse has good qualities too. And keeps the first horse very alert, of course. It is the company Synpac, represented by Dr. Blythe Devlin. Synpac is supported by Dr. Y.T.Chen from Duke University.

Synpac produces in fact the very same medicine but in a totally different way. It is a small company but backed up financially by a very heavy pharmaceutical company. So they do not perform the research themselves but do this by contract research. Which has advantages (little investment) but also disadvantages (contracts and lawyers I imagine). Also the way of manufacturing is very different. Synpac uses no animals, but fermentation. The medicine is brewed in a jacuzzi-like soup. I have no opinion on the relative qualities of both manufacturing processes, but Pharming/Genzyme is undoubtedly ahead at the moment.  Synpac however will also try to perform a trial with infants this year and juvenile/ adult trials next year. Problems with formulation (which means stable storage as I understood) are overcome, said Dr. Devlin, but she did not tell a lot more.

A disadvantage of the fermentation process seems to be (somebody told me) the low concentration of the difficult purification therefore. But there will be advantages too, no doubt.

And then, finally the last, black horse.Introduced expertly by Dr. Amalfitano from Duke University, NC, USA. Also cooperating with Dr. Y.T.Chen. This horse follows a different route, so it is not really the same race.

Pharming/Genzyme uses genetic modification in animals to produce the medicine (enzyme) but does not change any genes in the patient. Dr. Amalfitano and his people are working on a real gene therapy for the patient. The idea is there for years, but maybe there is a breakthrough coming soon! The point is not, how can you change genetic material, but how can you get the changed material in the muscle cells. Dr. Amalfitano explained a few tricks to do this. First the
genetic material need some transportation (vectors). This is found in viruses. You bring the material in relatively harmless viruses and infect the patient. The viruses are then mostly stored in the liver and afterward they produce a lot of the enzyme which is secreted in the blood.

So the viruses are not needed to go to every muscle cell,;the enzyme does, just like in the other two therapies. So there are some similarities between these therapies. There are still a lot of problems to overcome. For instance, the virus infection must, to be effective, last as long as possible. And afterward, once the infection is over, you can not use the same virus again, because the patient has produced antibodies.

Dr. Amalfitano was very convincing in the potential strength of this therapy. So probably this black horse will not win this race, but on the long run they may have a potentially very effective therapy. We will see and follow this with great interest, regardless which one of the other two wins the race.

In the end of the afternoon (our) Maryze and (our) Kevin gave their presentation.Impressive both and that is not just my opinion.

Maryze emphasized the importance of initiatives of patients and patient organisations. They played a very, very important role in organising and stimulating research and bringing parties together.

There are three main parties: patients/patient organisations ; research (universities/ hospitals) and industry. And these parties are surrounded by  social, political and economic forces. We have to be alert always and produce publicity and counter forces with the media if needed.We must also be critical towards the power of the industry. The medication must not only be become available, it must also be affordable. (By the way, nobody was willing tospeculate about the price of the Pompe drug). Maryze concluded with a moving story about her personal emotions during the turbulent events in the last years. How can you cope with all the new expectations? What if the hope is false? What if the drug is not regenerating, but only stabilises the disease? You have to be a very emotionally stable person to handle all this possibilities and expectations.

Kevin put his personal experiences (the diagnosis and death of his son) at the begin of his presentation. He emphasised the importance of knowledge by the patients. It is really of the greatest importance that Pompe patients and a lot of physicians will be much more aware. Kevin has a lot of humor but there are two things he hates: ignorance and bigotry. Good choice, but not easy ones to correct.

I forgot a lot. One interesting thing I like to mention. Mr Andrew Curtis from Genzyme proposed to initiate to establish in different countries Genetic Centres of Excellence. These institutes (maybe connected to a hospital) could support diagnosis, treatment, education and support for Pompe patients and other comparable diseases. A bit like the existing Centers for Respiratory Support we have in the Netherlands. A splendid idea. I hope they will discuss this further to

That is it for now. Confused? Never mind, that is a good state of mind. I hope I can give you part 2 tomorrow. Kevin and Maryze and others can fill you in about the discussions today an tomorrow later.

Bye, Gezinus

Part 2 (posted Sunday 4 July, 1999)


My second report from the IPA conference could be very brief: no real news. As you know, today the only and final speaker was Dr. Ans van der Ploeg, who leads the clinical trials for the Pharming/Genzyme treatment in the Sophia Hospital.

They started the phase 2 trials with 4 babies and 2 juveniles in january/february. The patients get the medicine (the enzyme alpha glucosidase) once a week intravenously. All trials subjects are still alive and tolerating the drug well.

As could be expected Dr van der Ploeg could not give us some prelimonary conclusions other than all seems to be going well, There are no indications that the treatment is  not working. Dr. van der Ploeg is a scientist, so she refused to draw any conclusions before it is really possible. The conclusions must be made according to objective criteria, on measurements of muscle strength or pulmonary function, not on the basis of impressions etc. The first real conclusions can not be expected before the fourth quarter of this year.

It was really pitiful to watch her trying very hard not to give answers to all the questions. You could feel that she really wanted to tell us all about what was going on at the trials but she just could not. But while she was telling us again and again that she could not give us any conclusions she was always smiling !! You should have seen her, trying very very hard not to tell us a lot of things she wanted badly to tell us.Which gave us in the audience the feeling that everything is really going very very well.

There is another indication to confirm this. Two of the babies are having their first anniversary. And as you know the majority of the Pompe babies do not reach this age unfortunately.

There were a lot of questions and very few answers. Some of us were a little disappointed I noticed afterwards. I was not in the least, because I knew before that there would be no hard conclusions, and what I heard gave me confirmation and confidence that all is going (very) well. Nothing more or better can be expected at this moment.

One important question and answer was: when will adult trials start. Answer: it is not sure that adult trials will be executed. The objective is to have the drug on the market as soon as possible. If this can be done without adult trials, then these will be omitted. As Dr. Reuser said strongly: in fact the adult trials have already been started, because there is no real difference between the infantile/juvenile form and the adult form of Pompe. So way have adult trials if this would just delay the introduction of the drug.

Other people (Kevin maybe) will tell you how the founding of the IPA has come along. I got the impression that evrything in that department also went all right. During and after the lunch today we said till next time, au revoir, auf wiedersehen, arriverdecci and tot de volgende keer to a lot of nice people. Hard to believe that we did not know them personnaly three days earlier. I am convinced that the conference will later show to have been very succesfull in particular because there have been a lot of personal contacts. Just to give an example, the people from Genzyme told me that they were really inspired by a conference like this. Meeting patients and patient organisations and academic people from another line of research.

So I was not disappointed because of the lack of hard news. On the contrary. Next year there will be news. I'm sure.


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