tag:blogger.com,1999:blog-52085624077887223072024-03-05T09:07:32.178+00:00Pompe disease - the real storyThe true story of the development of a treatment for Pompe disease.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.comBlogger80125tag:blogger.com,1999:blog-5208562407788722307.post-17296330844036180992017-12-12T16:10:00.000+00:002017-12-12T16:10:02.191+00:00What's next?<div dir="ltr" style="text-align: left;" trbidi="on">
I haven't updated this blog for a while and thought that I should probably do so, even if only so that the last word isn't the Duke negativity. I know that the information here is in a somewhat clunky format, so my project for the New Year is to turn it into something more reader-friendly. I say that with some confidence as I am going back to university, so will have more time to devote to it.<br />
<br />
At the risk of repeating myself, this is a great story that deserves to be known and understood, especially by the many patients now receiving enzyme replacement therapy around the world. Watch this space.</div>
Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-27284813079393640032012-08-22T22:16:00.001+01:002020-12-22T12:15:00.486+00:00The Duke "deception": what should be done?<div dir="ltr" style="text-align: left;" trbidi="on">
There is no cause more dear to me than the advancement of Pompe research. It is heartbreaking, plain heartbreaking, to see that cause tarnished in the way that it has been by the Duke paper. Science is about truth and evidence. There is very little room for short cuts and certainly none for spin. <br />
<br />
The 2001 Duke paper in <i>Genetics in Medicine</i> stands exposed as containing false information. It is now clear that this was a deliberate falsehood, for which an inadequate explanation has been given.<br />
<br />
Worse, that deliberate falsehood was used in the paper to argue against the work of another Pompe researchers, who used enzyme manufactured using a different method.<br />
<br />
There is an established course of action in such cases: the paper must be withdrawn. It would be best if the authors, recognising the enormity of their error, asked for this to be done themselves. Failing that, the editor of <i>Genetics in Medicine</i> should do so to protect the integrity of the journal. <br />
<br />
However, that is not the end of the matter. As we know, different companies were involved at this stage and the production method of alpha-glucosidase was itself a contentious subject. It is no exaggeration to say that fortunes were made or lost on that decision, on which the Duke paper may have had a bearing.<br />
<br />
My questions now are:<br />
<br />
Was anyone at Genzyme aware of the incorrect data reported in the Duke paper?<br />
<br />
Was anyone within the senior management at Duke University aware that data was being misreported in this way?<br />
<br />
Time to get digging, I guess!</div>
Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-38021599828301626762012-08-22T22:03:00.003+01:002012-08-22T22:42:08.483+01:00The Duke response<div dir="ltr" style="text-align: left;" trbidi="on">
In the 9 August advance online publication section of Genetics in Medicine, <a href="http://www.nature.com/gim/journal/vaop/ncurrent/index.html#09082012" target="_blank">two letters appear</a> . One is from Arnold Reuser <i><a href="http://www.nature.com/gim/journal/vaop/ncurrent/full/gim201280a.html" target="_blank">Inconsistent reporting about dosing, dosing regimen, and immunomodulation therapy in Pompe disease</a> </i>and a response from Andy Amalfitano, Priya Kishnani and YT Chen: <a href="http://www.nature.com/gim/journal/vaop/ncurrent/full/gim201281a.html" target="_blank"><i>Response to Reuser</i></a>.<br />
<br />
Once again, these are behind a paywall but let me precis.<br />
<br />
The letter from Arnold Reuser makes the observation that the dosage data reported in the 2001 genetics in Medicine paper on the Duke ERT trial is inconsistent with that reported in the 2012 paper from Banugaria <i>et al</i> as described in the last few blog entries. For an editor to publish this means that they consider that there is a case to answer. As indeed there is.<br />
<br />
Now, I have been awaiting the publication of the Duke response with some impatience, hoping that, somehow, there would be a reasonable explanation that would restore my belief in the integrity of researchers that I had admired.<br />
<br />
Unfortunately, it does not. Here is what it says.<br />
<br />
<blockquote class="tr_bq">
Dr Reuser is correct in noting that in our original report,<br />
we had not disclosed that in latter portions of the first clinical<br />
trial for patients 1 and 2 (who had declining AIMS scores and<br />
increasing antibody titers), that we attempted to treat these<br />
patients with increased doses of the enzyme,...</blockquote>
<br />
Going on to explain that:<br />
<br />
<blockquote class="tr_bq">
These attempts were ongoing during submission and review of our original<br />
manuscript, and were well beyond the scope of that manuscript,<br />
requiring further more detailed review and reporting as noted in subsequent publications</blockquote>
And finally concluding that their statement<br />
:<br />
<blockquote class="tr_bq">
“Three patients with<br />
infantile Pompe disease have been receiving twice-weekly<br />
intravenous infusions of rhGAA for 14 to 17 months,”</blockquote>
Might be better changed to:<br />
<blockquote class="tr_bq">
Three patients with infantile Pompe disease have been receiving<br />
at least twice-weekly intravenous infusions of rhGAA for<br />
14–17 months</blockquote>
And that actually appears as a correction to the 2001 paper in the current issue of genetics in Medicine. This is actually pretty jaw-dropping. Let me explain why.<br />
<br />
Firstly, the implication that the initial 5mg/kg twice weekly dose was changed so late in the course of the trial that it was just too complicated to include. Hardly worth mentioning, even. Well, the reported period was 14 -17 months. The dosage was changed after 20 weeks for Patient 1 and after 15 weeks for Patient 2. So for two thirds of the trial, the dose was much higher. The explanation given by Duke simply does not wash its face.<br />
<br />
Secondly, there is that section in the 2001 Duke paper still uncorrected:<br />
<br />
<blockquote class="tr_bq">
Similar cardiac improvements in four infants treated with rhGAA from rabbit milk for 9 months have recently been reported<sup><a href="http://www.nature.com/gim/journal/v3/n2/full/gim200127a.html#bib15">15</a></sup>;
however, the doses of rhGAA from rabbit milk necessary for the
therapeutic effects were 4 times higher than the present study of rhGAA
from CHO cells.</blockquote>
The conclusion is pretty clear. Incorrect dosage rates were deliberately reported in the 2001 paper, in order to put forward an argument against a rival group's work - a group which used enzyme manufactured via a different production method. This is deception, pure and simple, and has no place in science.</div>
Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-50770003860958606692012-07-27T18:41:00.001+01:002012-07-27T18:53:19.936+01:00Duke author admits discrepancy<div dir="ltr" style="text-align: left;" trbidi="on">
A bit of an update.<br />
<br />
Firstly, a letter from Dr Arnold Reuser pointing out the discrepancy in the data has been published in Molecular Genetics and Metabolism, as a 'Letter to the Editor':<br />
<a href="http://www.sciencedirect.com/science/article/pii/S1096719212001990" rel="nofollow" target="_blank">Enzyme therapy in Pompe disease: questions remain</a><br />
<br />
This was published online (link above) but unfortunately is behind their paywall, if you don't have a ScienceDirect subscription. The key sentence is:<br />
<br />
<blockquote class="tr_bq">
While Drs Y.-T. Chen, P.S. Kishnani and A. Amalfitano are authors<br />
on both publications, the information contained in Banugaria et al.,<br />
Mol. Genet. Metab. 2012;105:677–680 and Amalfitano et al., Genet.<br />
Med. 2001;3:132–138 is mutually inconsistent.</blockquote>
This has been followed by a response from Dr Kishnani at the other authors of the 2012 paper. Again, it is a <a href="http://www.sciencedirect.com/science/article/pii/S1096719212002454" rel="nofollow" target="_blank">Letter to the Editor </a>of Molecular Genetics and Metabolism. And again it is behind a paywall - sorry. However, the key part is:<br />
<br />
<blockquote class="tr_bq">
The details of the ERT dosing and immunomodulatory regimens<br />
used in the management of this patient are accurate as described in<br />
our recent article in Molecular Genetics and Metabolism [2]. The details<br />
of the increased rhGAA dosing and immunomodulation were<br />
not included in the 2001 Genetics in Medicine paper for reasons outlined<br />
in a recently accepted letter to the editor submitted in Genetics<br />
in Medicine by Drs. Amalfitano, Kishnani and Chen [3].</blockquote>
So it is accepted that the 2001 data <i>were incorrect</i> and that the 2012 data are correct. They go on to say:<br />
<br />
<blockquote class="tr_bq">
We regret any confusion this may have caused.</blockquote>
So, we await the publication of the letter in genetics in Medicine which will explain why the data was withheld in 2001. I'm struggling to see what could be in this letter than will somehow make things OK. For the record though, I would be absolutely delighted to be surprised.</div>Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-177713940927295852012-07-26T22:12:00.003+01:002012-07-27T18:48:54.357+01:00Why does the Duke error matter?<div dir="ltr" style="text-align: left;" trbidi="on">
Right. As you know, I like to keep things as objective as possible. So I give fair warning that following one more excursion into the land of facts and evidence, I will give my subjective opinion.<br />
<br />
First, more evidence. Let's return to that <a href="http://www.nature.com/gim/journal/v3/n2/full/gim200127a.html" rel="nofollow" target="_blank">2001 paper</a>. As I've shown, it repeatedly describes the dosage regime used in the trial as 5mg/kg. Now, as you know, an earlier trial in Rotterdam had already been published in <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2800%2902533-2/fulltext#article_upsell" target="_blank">The Lancet</a> in 2000. Here's how the Duke paper refers to the Rotterdam trial:<br />
<br />
<blockquote class="tr_bq">
Similar cardiac improvements in four infants treated with rhGAA from rabbit milk for 9 months have recently been reported<sup><a href="http://www.nature.com/gim/journal/v3/n2/full/gim200127a.html#bib15">15</a></sup>;
however, the doses of rhGAA from rabbit milk necessary for the
therapeutic effects were 4 times higher than the present study of rhGAA
from CHO cells.</blockquote>
<br />
To be clear, the two trials each used enzyme produced by a different method. Rotterdam used enzyme produced in the milk of transgenic animals, whereas Duke used enzyme produced by CHO cells in culture. The Duke paper is explicitly stating above that their method was <i>better</i> because the dosage used was <i>lower</i>.<br />
<br />
In other words they were making an argument based on dosage data that they presumably knew to be false.<br />
<br />
And now the subjective part:<br />
<br />
This wasn't a case of careless error-checking. It's hard to avoid the conclusion that this was a deliberate omission of data, designed to support the argument that a specific product required a lower dose - an argument now shown to be false.<br />
<br />
As a scientist, I find this absolutely shocking. It is a violation of the standards of openness and transparency on which good science relies. <br />
<br />
The question is why this occurred. It's probably worth bearing in mind that, once ERT had been shown to work, there was obviously money to be made. And where that money went would depend on the method chosen to produce the enzyme. As you know, the CHO cell method described in the 2001 paper was the production method chosen.<br />
<br />
There's also the fact that credit for ERT for Pompe disease is a big thing - perhaps having published last, the temptation to try to gain priority over the previous publication was too much to resist.<br />
<br />
Or perhaps, in some way and for some as yet unknown reason, the authors managed to convince themselves that it was OK to withhold the data in the service of some greater good. A human failing - politicians do it all the time - but not one allowable in science.<br />
<br />
I have some thoughts on what should happen next but time for a breather. <br />
<br />
<br /></div>Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-44127630336607164482012-07-26T21:44:00.002+01:002012-07-26T21:44:27.032+01:00What is wrong with the Duke publication?<div dir="ltr" style="text-align: left;" trbidi="on">
As regular readers will know, I'm all for keeping things simple. However this is serious and in order to explain why it is serious I'm afraid that there is no option but to delve into the detail. You might want a coffee beside you at this point. OK? Right, here we go.<br />
<br />
First stop, 2001 in that original Duke paper in <a href="http://www.nature.com/gim/journal/v3/n2/full/gim200127a.html" rel="nofollow" target="_blank">Genetics in Medicine</a>. This paper reported the results on the 3 patients in the Duke ERT trial. Now, the actual end results - the evidence that ERT works - are not in question. The problem lies in the 'dusty end' of the paper, the Materials and Methods. Here the enzyme dosage given to the patients is described as 5mg/kg, twice weekly. Under Results, we are told that the enzyme was given for 14-17 months and again the twice-weekly 5mg/kg dosage is mentioned. There is one further reference to the dosage that I'll come to later, however the message is clear: the paper describes the results of 3 patients treated with a dosage regime of 5mg/kg, twice-weekly.<br />
<br />
On to 2004, and the publication of a paper by Hunley <i>et al:</i><br />
<br />
<br />
<blockquote class="tr_bq">
<div id="article-title-1" itemprop="headline" style="text-align: left;">
<b>Nephrotic Syndrome Complicating α-Glucosidase Replacement Therapy for Pompe Disease</b></div>
</blockquote>
<cite><a href="http://www.blogger.com/goog_661021626"><abbr class="slug-jnl-abbrev" title="Pediatrics">Pediatrics</abbr>
<span class="slug-vol">
Vol. 114
</span><span class="slug-issue">
No. 4
</span></a><span class="slug-pub-date" itemprop="datePublished"><a href="http://pediatrics.aappublications.org/content/114/4/e532.full.html" rel="nofollow" target="_blank"> October 1, 2004</a> </span></cite><br />
<br />
(Full text available free <a href="http://pediatrics.aappublications.org/content/114/4/e532.full.html" rel="nofollow" target="_blank">online</a>)<br />
<br />
This shares 3 authors with the 2001 paper, Drs Amalfitano, Chen and Kishnani and reports the case of a child on ERT who developed complications. However, the dosage rate is rather different from that described in the 2001 paper. This paper describes a dosage of 5mg/kg, twice-weekly (20mg every 2 weeks), for 15 weeks, followed by 10mg/kg ,twice-weekly (40mg/kg every 2 weeks)for 27 weeks, followed by 5x10mg/kg weekly (100mg per 2 weeks)for 11 weeks.<br />
<br />
However, at no point in this paper is it explicitly stated that this patient was one of the three described in the 2001 results. So we might give Duke the benefit of the doubt (at this point, I don't think I do).<br />
<br />
Fast forward to 2012 and the following publication from Banugaria <i>et al</i>:<br />
<br />
<blockquote class="tr_bq">
<h1 class="svTitle">
<span style="font-size: small;">Persistence of high sustained antibodies to enzyme
replacement therapy despite extensive immunomodulatory therapy in an
infant with Pompe disease: Need for agents to target antibody-secreting
plasma cells</span></h1>
</blockquote>
<div class="title">
Molecular Genetics and Metabolism</div>
<a href="http://www.sciencedirect.com/science/journal/10967192/105/4" title="Go to table of contents for this volume/issue">Volume 105, Issue 4</a>, April 2012, Pages 677–680<br />
<br />
(<a href="http://www.sciencedirect.com/science/article/pii/S1096719212000236" rel="nofollow" target="_blank">abstract only</a> available free) <br />
<br />
This papers shares 3 authors with the 2001 paper, Drs Amalfitano, Chen and Kishnani, and it refers back explicitly to one patient in that study, however the results reported are rather different. Rather than a dosage of 5mg/kg for 17 months, this paper tells us that patient 1 received: 5mg/kg twice weekly (20mg every 2 weeks)for only the first 5 months, followed by 10mg/kg twice-weekly (40mg every 2 weeks) for 8 months and then 5 X 10mg/kg weekly (100mg every 2 weeks) for 4 months.<br />
<br />
It is fair to say then that the 2001 paper which purported to describe a treatment regime of 5/mg/kg, twice-weekly, does no such thing. On the evidence of the 2012 paper, <i>at least</i> one of those patients had a much higher dosage for most of the study.<br />
<br />
Apologies once again for all the detail. The point is to allow you to check what I've said for yourself.<br />
<br />
Now at this point you may be thinking "OK, so the 2001 paper had wrong information in it. A simple error that any of us could have made - does it matter?" Yes, it does matter. It matters a great deal. And I shall explain why in my next post.<br />
<br /></div>Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-38413376854662899072012-07-26T20:21:00.000+01:002012-07-26T20:21:59.836+01:00One last twist in the tale<div dir="ltr" style="text-align: left;" trbidi="on">
Well, here's a story that I wasn't expecting to have to write. If you've followed the Pompe story through this blog (and if not, why not?), then you'll know that there have been occasional patches of...murkiness. Times when things have happened that the reader may have had to stretch to see in a good, or even neutral, light.<br />
<br />
Nearly all of those have been concerned with commercial interests and, well, I think you kind of expect it from that quarter, where the bottom line reigns supreme. At least, I thought, the same could not be said of the world of academic science. A world where truth and objectivity were tirelessly in the service of the scientific ideal. You know, the <i>good</i> guys.<br />
<br />
Turns out, I was wrong. There are significant errors - errors which are difficult to explain - in the original publication of the ERT trial results from Duke University, one of the most important publications in the development of ERT.<br />
<br />
The publication in question is:<br />
<blockquote class="tr_bq">
Recombinant human acid a-glucosidase enzyme<br />therapy for infantile glycogen storage disease<br />type II: Results of a phase I/II clinical trial</blockquote>
Amalfitano <i>et al </i>Genetics in Medicine, 2001:<b>3</b>(2):132–138<i>.</i> <br />
<br />
The full text is available <a href="http://www.nature.com/gim/journal/v3/n2/full/gim200127a.html" rel="nofollow" target="_blank">online</a>.<br />
<br />
Over the next few posts, I will spell out exactly what the issue is, why it matters and what I think should be done.</div>Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-50804097370336100672010-02-06T18:28:00.003+00:002010-02-06T18:32:14.612+00:002003 - onwards and upwards2003 signaled the end of one era and the beginning of another. From now on, news of friends receiving ERT would begin to come thick and fast - every one of them a cause for rejoicing. <br />
<br />
It would take until 29 March 2006 (Europe) and 28 April 2006 (USA) before the formal approval of Myozyme as a treatment. However even that was not the end of the road - there are still issues around funding and, above all, ERT is a treatment, not a cure.<br />
<br />
<br />
The fight goes on, carried out by an international community of patients, scientists, doctors and companies. I hope that others will contribute the rest of the story here.<br />
<br />
<br />
I myself 'retired' from the Pompe scene at the end of 2003. It had been 10 years since Calum died and my dream of seeing an effective treatment for Pompe disease had come true. We wanted to remember our son for his short, but wonderful, time with us and not for his disease. There were other people better suited than I to do my remaining jobs. It was time to move on.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-31078215410765896202010-02-06T18:20:00.001+00:002010-06-13T11:07:16.513+01:00HeidelbergI go to many conferences as part of my work as well as personal activities and I can honestly say that the 2003 IPA conference remains the best I have ever been to. It was held on 31 October- 2 November, in Heidelberg, Germany. Everything was superb: the location, the presentations, the cameradie, the beer...<br />
<br />
The conference <a href="http://home.arcor.de/fobrokel/pompe2003/index.html">website</a> and <a href="http://home.arcor.de/fobrokel/pompe2003/indexfollowup.html">follow-up</a> (including proceedings) are still available to read for yourself.<br />
<br />
There was also a <a href="http://worldpompe.org/index.php/news/article/389/">Q and A session</a> released on the website and GSDNet.<br />
<br />
That the conference was such a roaring success is in large part down to the organisers, Thomas Schaller, Birgit Wolf, Rita & Helmut Erny from the German patient group.<br />
<br />
<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg0G5KSTwViFelIzJz_WRJNSmPB5KfppR2GO6ybqZCtloraE4i4GujaN80LFc0l1X_iKH02k6orAiQEuAMItBMVcSylOhLCBhi3pUN83eb9XjIQMaxqPalMDXPwFer_8BMqmrdDxg-scoA/s1600-h/Conference+Participants2003web.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="273" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg0G5KSTwViFelIzJz_WRJNSmPB5KfppR2GO6ybqZCtloraE4i4GujaN80LFc0l1X_iKH02k6orAiQEuAMItBMVcSylOhLCBhi3pUN83eb9XjIQMaxqPalMDXPwFer_8BMqmrdDxg-scoA/s640/Conference+Participants2003web.jpg" width="640" /></a></div><div style="text-align: center;"><span style="font-size: x-small;"><i>Conference participants</i></span></div><div style="text-align: center;"><br />
</div><br />
However one other reason is that, here, for the first time, much of the talk was about success. Successful trials, successful enzyme production and the prospect of many more people being treated in the coming year. We had come a long way.<br />
<br />
There was still a long way to go, of course, but as Marilyn House put it at the time " everyone came away with new sense of enthusiasm and cooperation for the treatment of Pompe's disease."<br />
<br />
<br />
<br />
Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-90684474244733503352010-02-06T17:16:00.001+00:002010-02-06T17:21:57.413+00:002003Before we get into the 2003 big picture, can I just step aside for a moment and mention something of huge significance for me. This was the year that, for the very first time, there was a UK clinical trial of ERT. This was at The Willink Centre in Manchester, under Dr Ed Wraith and co-workers. This was a dream come true and added to a growing feeling that my own part in the story, such as it was, was coming to a logical end.<br />
<br />
2003 was again a year of solid progress. In retrospect, we had moved pretty clearly to a situation where we knew that ERT <i>would</i> be available. For many people, this was even more difficult than wondering <i>if</i> it would be available. It was now a waiting game, not a hoping game. In particular, many adult patients were wondering when it would be their turn to feature in a trial.<br />
<br />
This led to occasional tensions. The IPA were in regular contact with Genzyme, yet much of this was under strict terms of confidentiality. This meant that information could not be passed on to the patients, who were - understandably - restive.<br />
<br />
Nevertheless, a series of regular updates held things together.<br />
<br />
Issue 10 of the <a href="http://www.pompe.org.uk/images/stories/pompebulletin10.pdf">Pompe's Bulletin</a> came out in February, bringing people up to date on a whole range of things, including the Manchester trial.<br />
<br />
There were regular Pompe Program updates (contents agreed between the IPA and Genzyme) of progress.<br />
<br />
These were released on <a href="http://worldpompe.org/index.php/news/article/393/">February 18</a>, <a href="http://worldpompe.org/index.php/news/article/392/">March 19</a> (Genzyme press release), <a href="http://worldpompe.org/index.php/news/article/390/">September 10</a> (press release)<br />
<br />
The latter brought the first news of adult onset trials and of 'Special Access' for patients who did not fit into clinical trials but who were in demonstrable need. This was a mark of Genzyme's success in ramping up production - they could not have made such promises without absolute confidence in supplies of enzyme. From now on, alpha-glucosidase would be much more widely available, in advance of formal commercialisation.<br />
<br />
As you can imagine, having been aware of developments through regular contact with Genzyme, it was a great feeling of relief to have them out in the public domain. It was recognised though that something bigger and public was needed to signal progress to patients. That something was the biggest and best Pompe event so far - the 2003 IPA Conference at Heidelberg in Germany.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com1tag:blogger.com,1999:blog-5208562407788722307.post-90669514078624209322010-01-31T20:35:00.006+00:002010-02-01T13:54:41.308+00:00Maryze's story - Part 8<div class="separator" style="clear: both; text-align: center;"></div>On March the 29th Myozyme was officially approved in Europe. That special day for Pompe patients, I was at the funeral of a Pompe patient I knew very well. It was she who called me that day on November the 14th 1996, to ask if I had heard the news and what I thought of it. It was sad that she never could benefit from the treatment she too had been waiting for so long. Shortly after the FDA approved Myozyme as well. Slowly Pompe patients all over the world did start treatment. I know of one boy in Germany who was so affected that he didn’t meet the criteria for participation in the clinical trial in Rotterdam, but he was able to start commercial treatment with Myozyme just 2 weeks after the official approval. <br />
<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEibu29jLsLu3ZSfqwe0fII4LCnQQOZeM76t_zG33gopcamRdJLE1AzEKMZzaKUifJsFCg96TYjdO5O8Whu74YsuYKDbwNaKhxUBkn31auYxuPdNIZRT31pbt3IvWTTw_vfRAdEVkr-IsEQ/s1600-h/maryze12.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="247" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEibu29jLsLu3ZSfqwe0fII4LCnQQOZeM76t_zG33gopcamRdJLE1AzEKMZzaKUifJsFCg96TYjdO5O8Whu74YsuYKDbwNaKhxUBkn31auYxuPdNIZRT31pbt3IvWTTw_vfRAdEVkr-IsEQ/s400/maryze12.jpg" width="400" /></a></div><br />
<div class="separator" style="clear: both; text-align: center;"></div><div style="text-align: center;"><span style="font-size: x-small;"><i>A cake to celebrate the approval of Myozyme.</i></span></div><br />
In spite of the approval the clinical trials on Myozyme in adults continued. The regulatory authorities had requested additional data that showed also efficacy of Myozyme in older Pompe patients. I personally admire these people who did continue going to Rotterdam and other trial sites in France and the USA to get their infusions not knowing if they received alpha-glucosidase or placebo, to do all the required tests and go through all the emotional feelings, even when they knew Myozyme was approved for the market already. <br />
<br />
Over the years from 1996 till now, I collected a lot of documents, newspaper articles, publications etc on Pompe disease and related issues from all over the world. These 6 large files contain a lot of information on events and people not mentioned in the book ‘The Cure’. This book is a story of John Crowley and his family, but it's not the story of so many other Pompe patients in the world.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com1tag:blogger.com,1999:blog-5208562407788722307.post-14983172713095768552010-01-31T20:33:00.002+00:002010-02-01T00:11:33.239+00:00Maryze's story - Part 7In December 2005, Genzyme invited me to join them and Dr. Ans van der Ploeg to the official hearing at the European Medicine Agency (EMEA) in London. Genzyme had received permission from the EMEA to bring a patient to the official hearing to give her personal account. I immediately said ‘yes’, because it was important for all Pompe patients in Europe and beyond to get approval for the enzyme replacement therapy. At December 13 2005, it was the day of truth and it was one of the most exciting days in my life. We were all nervous, even after such a thorough preparation. Genzyme and Dr. Ans van der Ploeg gave an excellent and clear presentation on the effect of ERT. After their presentation it was my turn.<br />
<br />
I had 5 minutes to tell about my personal experience with enzyme replacement therapy. For me these 5 minutes was worse than doing 3 school exams. I felt as if all the European patients were sitting on my shoulder, depending on my performance and ability to explain the impact of ERT on my life. All the experts in the room were silent and listened carefully. I was able to tell them the story behind the data Genzyme and my physician presented. This mixture of hard scientific data and a personal account was good and clear. After the official hearing we received a debriefing of the French and Belgium representatives who were leading this hearing. The French representative told us that apart from the data, my personal story was what they wanted to hear. Sometimes hard data can’t tell what one story can explain…the real impact of a treatment on a life.<br />
<br />
On January the 27th 2006 we were told in a press release that Myozyme™ Receives Positive Opinion from European Regulatory Committee (London, 27 January 2006, Doc. Ref. <a href="http://www.ema.europa.eu/pdfs/human/press/pr/3279606en.pdf">EMEA/32796/2006</a>). This meant that the regulatory committee would advise the European commission to approve Myozyme for Pompe disease. Just before this press release I was called by Genzyme by someone I know very well. He just asked me: ‘Do you have Champagne?’ Tears ran below my cheeks, as I felt so relieved that now all Pompe patients in Europe could start treatment and I knew other countries would follow Europe. We were both emotional and happy. It was as if we won a battle together and survived. One day after this press release, on January the 28th 2006, the VSN had organised a Pompe patient meeting. It couldn’t have be timed better and in a movie one wouldn’t belief it as it would be too good to be true. At that meeting Pompe patients from all over the Netherlands gathered and prepared to hear another delay in treatment as we had been hearing for so many years already. Someone of Genzyme did tell everyone about the press release, that most of the people didn’t know about yet as it was so fresh, but the message wasn’t understood. Then my mother decided to tell everyone this good news in a symbolic way.<br />
<br />
She left the room and came back with a bottle of Champagne and some glasses. She entered the stage and called several people to get a glass of Champagne. Dr. Arnold Reuser, Dr. Ans van der Ploeg, Willem van Weperen (Genzyme), Gezinus Wolters, my father, and I. We all represented those who were so closely involved in the process of getting a treatment: scientists, physicians, industry, patient organisation, patients, parents and partners.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhP0suZlTsYrG7ua1CJnQhdFnGQxvddCZD_YyB99UM1zykFECvzM-egrWIeQsqdUZTuVQs0sGHXesSIYorA3q-9MO_hVBha-2XV_bYDhN4twqn1g2y6-H9IMHTDfeNcu2qLCbUWpPz3rOg/s1600-h/maryze10.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="295" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhP0suZlTsYrG7ua1CJnQhdFnGQxvddCZD_YyB99UM1zykFECvzM-egrWIeQsqdUZTuVQs0sGHXesSIYorA3q-9MO_hVBha-2XV_bYDhN4twqn1g2y6-H9IMHTDfeNcu2qLCbUWpPz3rOg/s400/maryze10.jpg" width="400" /></a></div><div class="separator" style="clear: both; text-align: center;"><i><span style="font-size: x-small;">My mother, Tanneke van der Linde, and Dr Arnold Reuser opening a bottle of champagne.</span></i> </div><div class="separator" style="clear: both; text-align: center;"><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUdNuJx5dU1XXyvy7M5mxXzkX__4vfOKi_TJIFXmrL3gA7VvxJJGzzsyzFqYwsNZ-7keDa54o-rE8FUUTeVIvJySTkSVuU7iKPdigiKeiVk71VEj0HJGObN2jM3yuINTiZIOOnYC1hSFA/s1600-h/maryze11.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="351" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUdNuJx5dU1XXyvy7M5mxXzkX__4vfOKi_TJIFXmrL3gA7VvxJJGzzsyzFqYwsNZ-7keDa54o-rE8FUUTeVIvJySTkSVuU7iKPdigiKeiVk71VEj0HJGObN2jM3yuINTiZIOOnYC1hSFA/s400/maryze11.jpg" width="400" /></a></div><div class="separator" style="clear: both; text-align: left;"><br />
</div>When the Champagne was poured in the glasses, everyone started slowly to understand. It took a while as no one really could belief it. After all those years of waiting since 1996, there finally a treatment would be available. This was the moment everyone was waiting for so long. Some people got emotional and hardly could express their feelings. Later I received an email from a patient who thanked me as she couldn’t say it personally, because she was afraid to cry. In the afternoon of Monday the 30th of January 2006, our doorbell rang. I was surprised to see a fellow Pompe patient and his wife at my door. They live not very far from me and decided to give me a bouquet of flowers for the work that I had done. I was deeply touched, because it was for people like him that I hoped the treatment would help. From now on when a new Pompe patient would be diagnosed, they would be told: ‘I am sorry to tell you that you have Pompe disease, but there is a treatment available’.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-41096927451260857932010-01-31T20:22:00.001+00:002010-01-31T23:05:10.668+00:00Maryze's story - Part 6In April 2002, I met John Crowley, former CEO of Novazyme and at that time working for Genzyme at a meeting. I also knew he had two children with Pompe disease and both were severely affected. John and my mother sat next to eachother and talked about their children: Megan, Patrick and me. I saw two parents who were both very worried about their children. They cried together. This is how I remember John, crying with my mother as they both saw their children deteriorating and didn’t know if treatment would come in time. <br />
<br />
Both his children, Megan and Patrick and I finally received our treatment on time. The opportunity to receive treatment was a gift of life. I told my physician, Dr. Ans van der Ploeg that I wanted to contribute to the knowledge of enzyme replacement therapy like the other patients were doing in the clinical trial. A muscle biopsy was taken and all neurological, lung and blood tests were done. These outcomes were also used in the data gathering to get approval for enzyme replacement therapy at the regulatory authorities. It was good to see that also other patients were able to start treatment. It was a time in which Anton and I regularly drank German Sekt to celebrate the start of treatment from a friend somewhere in the world. <br />
<br />
Through the contacts with patients world wide, the IPA learned that it was important to inform Pompe patients about the issues involved in Pompe disease such as breathing problems, common health problems, exercises and physical therapy, pregnancy, genetics, medical developments etc. We felt that people should know how to stay in a as good physical condition as possible. Especially regarding the breathing problems that can occur we felt Pompe patients should know how to treat it and what to do and especially what not to do, like for example using oxygen or using a C-pap. To inform as many Pompe patients as possible, The Pompe Connections were written and reviewed by medical experts from several countries. Later it was translated in several languages such as Japanese, Turkish, German, Spanish, French and Dutch.<br />
<br />
<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhOIIOdQxq0VVV3sb4LtdVLRDUGa-HJkbhYBNCACT8se5ruGYxzTq9zJ4nMXrOCzDOk5E1XWC_dxgyTdocyAFFBuAVqQsQ1bppz8szNEumrXQtKU7Jr6ViiYNEav2i3Vux837vcbU_bnbo/s1600-h/maryze6.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="355" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhOIIOdQxq0VVV3sb4LtdVLRDUGa-HJkbhYBNCACT8se5ruGYxzTq9zJ4nMXrOCzDOk5E1XWC_dxgyTdocyAFFBuAVqQsQ1bppz8szNEumrXQtKU7Jr6ViiYNEav2i3Vux837vcbU_bnbo/s400/maryze6.jpg" width="400" /></a> </div><div class="separator" style="clear: both; text-align: center;"><br />
</div>Later I heard that people around the world were very happy with this information, especially when it was in their own language. It was a tremendous task, but absolutely worth all the energy and effort.<br />
<br />
In November 2003, the International Pompe Association organised an international conference in Heidelberg, Germany. Scientists, physicians, patients and industry were present and shared the latest information on research. It was at that conference a mystery was solved. The mystery of the ‘Holy Grail’, the treatment Novazyme had been working on, but that suddenly disappeared. This statement of ‘Holy Grail’ is not mine, but Novazyme used this terminology in one of their press releases.<br />
<br />
In answer to a question, Dr. William Canfield told everyone at the conference that during a test with muscle cells stored with glycogen in a Petri dish where they added the ERT of Novazyme, a huge mistake was made. At first it was claimed that the Novazyme treatment was working so well that in just a couple of minutes the glycogen in these muscle cells was decreased to almost zero. Based partly on this result the Pharming ERT was wiped from the Pompe development program, as according to the results of that famous test it was the most inefficient treatment. Later it was admitted that the Pharming ERT should have been tested in vivo (experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment) as it would have been more fair and probably would have revealed that it was more effective in vivo than in vitro (experimentation done in live isolated cells). Genzyme was presented the great results of Novazyme and convinced that the treatment Novazyme was developing was indeed very promising.<br />
<br />
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<div style="text-align: center;"><i>Novazyme's mistake</i></div><br />
Genzyme bought Novazyme in 2001, the company of John Crowley, for millions of dollars. John Crowley was offered the position of senior vice president at Genzyme Therapeutics after the sale. The take over from Novazyme by Genzyme was investigated thoroughly by the Federal Trade Commission. While this investigation was still going on, it became clear that the Novazyme treatment wasn’t promising at all, but that its results were based of a mistake. While doing the test, the in vitro muscle cells weren’t fixed, so when the Novazyme treatment was added, the glycogen simply was washed away. In such a situation even plain water would have been able to remove the glycogen from muscle cells.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-24748942627097692662010-01-31T20:10:00.005+00:002010-01-31T23:03:36.942+00:00Maryze's story - Part 5Meanwhile in 1999 the <a href="http://www.worldpompe.org/">International Pompe Association</a> was founded. One year before, in 1998 at the annual patient meeting of the VSN in the Netherlands, also some parents from other countries such as Germany, UK, USA and the Netherlands, were present. After the annual meeting we came together in a separate meeting and it was discussed how we could work together on behalf of all Pompe patients in the world. Also for those who didn’t have a strong patient organisation in their country. It was at that particular meeting the name International Pompe Association was mentioned. One year later the IPA was officially established and registered. The first board members of IPA were: Kevin O’ Donnell (UK), Ria Broekgaarden (the Netherlands), Bob Morrisson (Australia), Randall House (USA), Thomas Schaller (Germany) and Maryze Schoneveld van der Linde (the Netherlands). <br />
<br />
In April 2000, at Easter, Anton and I went on holiday in Andalusia, Spain. I always wanted to see the beautiful Moorish architecture of the Alhambra near Granada and the Mesquita in Cordoba. When we returned home, my parents told us that Genzyme would stop the development of human alpha-glucosidasis in rabbits. For us this news was a complete shock as the Lancet had just published a convincing article that showed that enzyme replacement therapy was safe and effective in children with infantile onset Pompe disease (Van den Hout H, Reuser AJ, Vulto AG, Loonen MC, Cromme-Dijkhuis A, Van der Ploeg AT. Recombinant human <span lang="NL" style="font-family: Georgia; font-size: 12pt;">α</span>-glucosidase from rabbit milk in Pompe patients.<a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2800%2902533-2/fulltext#article_upsell"> Lancet 2000; 356:397-398</a>). Many Dutch Pompe patients were emotional about this decision. The dutch company Pharming that we got to know so well from the beginning and that had proved to have a treatment that was effective, was now put aside without getting a real treatment in return. The treatment that would be further developed had still to be proven effective at that time <br />
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<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi5IwNzUHKdov7tB5MCv3STpP7kosdNf8vKaGsDHJ6vx5YDGco_UCj9i_O_yHQeOsM2zyzJj9L_4T-rADclpmqhrlLKTMyHqQmIolKfvnc5KZSN8gkYqzIkASWIItdIH1XXdqj-_1773Mk/s1600-h/maryze5.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="263" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi5IwNzUHKdov7tB5MCv3STpP7kosdNf8vKaGsDHJ6vx5YDGco_UCj9i_O_yHQeOsM2zyzJj9L_4T-rADclpmqhrlLKTMyHqQmIolKfvnc5KZSN8gkYqzIkASWIItdIH1XXdqj-_1773Mk/s400/maryze5.jpg" width="400" /></a> </div><div class="separator" style="clear: both; text-align: center;"><span style="font-size: x-small;"><i>The decision to stop production of the rabbit enzyme received extensive coverage in the Dutch press </i></span></div><div class="separator" style="clear: both; text-align: center;"><br />
</div>On September 28, 2001 Genzyme completed the take over of Oklahoma City-based Novazyme. <br />
<br />
On October 30, 2001 Genzyme acquired the manufacturing facility in Geel, Belgium. In a pressrelease the following was said: ‘CAMBRIDGE, Mass.-Genzyme Corp. announced today that it has acquired certain assets of Pharming N.V., the Belgian subsidiary of the Pharming Group currently operating under a court-supervised receivership. These assets include a 70,000 square foot cGMP protein manufacturing facility currently under construction and a pilot plant that is currently used to produce transgenic human alpha-Glucosidase, both located in Geel, Belgium. The acquisition has been approved by the Commercial Court in Turnhout, the Province of Antwerp, and Genzyme's board of directors. In the near term, the acquisition of the Geel facility is intended to allow Genzyme to assume control over the production of the transgenic enzyme and secure its supply to nine patients with Pompe disease participating in the extension of a clinical trial. Genzyme has been solely funding the production of the enzyme since Pharming Group sought receivership’.<br />
<br />
When we heard about the financial problems of Pharming. It was a shock to all of us. Who would have ever thought that the company that was developing and producing our treatment was not able to manage and continue the production? It was a real nightmare and it made clear that even when a treatment is successful, the race isn’t finalised. Patients always will be in a vulnerable position as they always will be dependent on markets, CEOs, politics, researchers, physicians, governments etc. <br />
<br />
When Pharming had financial problems it became a difficult period for patients, physicians and the employees of Pharming. At a certain moment there wasn’t even money to pay salaries of those people who were producing the ERT in Geel, Belgium. Most of these people were young, just starting their carreer. I really was impressed with their persistence and loyalty to continue working for those 9 Pompe patients in the Netherlands and Germany who were depended on their ERT. They even continued working when they didn’t know if they would receive a salary for it. The problems of Pharming and especially the threads of the financial problems for the Pompe patients were discussed in the news. <br />
<br />
When Genzyme finally took over the Pompe program from Pharming. The employees in Geel were taken over as well. Most of these employees stayed at Genzyme to continue producing the ERT with the genetically modified rabbits. Many of them still work there and are closely involved in the Myozyme production in the 4000 Liter bioreactors in Geel.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-33189817155887833572010-01-31T20:00:00.002+00:002010-01-31T23:04:03.640+00:00Maryze's story - Part 4In 1998, Pharming and Genzyme started to work together in a joint venture.<br />
<br />
In 2000 Pharming started with the building of the factory in Geel, Belgium. This plant later was bought by Genzyme and now Myozyme in the 4000 Liter bioreactor is being produced. So in the end our treatment was being produced there after all.<br />
<br />
However who would think that everyone was happy with these developments, is mistaken. The animal welfare organisations were criticizing the use of animals for medicines. For Pompe patients in the Netherlands it was quite shocking to hear this. For us the development of the production of ERT in rabbits was the only chance we got and then animal welfare organisations and animal right activists were opposed to it? Did they really prefer the life of rabbits over the life of human babies?<br />
<br />
Greenpeace too was opposed to this development. I knew they were opposed to biotechnology anyway as their billboard posters showing their opposition of this technology had hung everyone in Leiden. Although at that time Pompe disease, wasn’t in the picture yet. At a debate on animals and biotechnology in the Dutch parliament, my father and I too were present. I just wanted to show everyone that I was serious and would fight to secure treatment for Pompe patients.<br />
<br />
During the break of the debate, a lady came up to me and my father while we were having coffee. She introduced herself and said she was working for Greenpeace. I was honestly a bit shocked and thought by myself well here it is, now I need to use all my arguments to make clear why I am in favour of human babies instead of rabbits. Then however the lady of Greenpeace continued saying: ‘Greenpeace still is opposed to medical treatments produced in animals, but when it comes to treatments for diseases for which no other treatment yet exists and for which animals are the only solution, we will make an exception. Then we will not oppose it. I just want you to know about this’. I was relieved. I didn’t need to go into discussion with Greenpeace. They too cared for human babies who otherwise would die. The fight however wasn’t over yet. <br />
<br />
On a normal day I was sitting behind my computer I suddenly heard a commercial on the radio. A voice was telling about a little boy who did love rabbits, but these rabbits were misused to get a treatment for Pompe disease, while another production method without animals also could be done. Listeners who also were opposed to this misuse of animals could donate money to the foundation against animal lab testing (Proefdiervrij). When I heard this I was shocked. What other production method was available? At that moment the transgenic rabbits were the only ones and 7 people were successfully treated with this. How could they say such a thing?<br />
<br />
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<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhvXQzFVKU4Gxiha0sR4lz8jxNSDEI9n9a4uOhQvJ4dShjqDRWCq5gt0B93OWJS9kPLPH769nsGrCol8rhuKGPH-THX7CJOL5IMwWG90tgpGr0Nc9FCZ4-yCJpSHILFnQRTNtyY_LlJ37I/s1600-h/maryze4.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="325" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhvXQzFVKU4Gxiha0sR4lz8jxNSDEI9n9a4uOhQvJ4dShjqDRWCq5gt0B93OWJS9kPLPH769nsGrCol8rhuKGPH-THX7CJOL5IMwWG90tgpGr0Nc9FCZ4-yCJpSHILFnQRTNtyY_LlJ37I/s400/maryze4.jpg" width="400" /></a> </div><div class="separator" style="clear: both; text-align: center;"><i>Animal rights lies. The Pompe community fights for the truth - and not for the last time.</i> </div><br />
I immediately called the VSN. They too heard the commercial that meanwhile had been repeated several times on several radio stations already. This foundation also had a big advertisement in one of the national newspapers in the Netherlands, giving the same statement. In that advertisement a boy of about 6 years old was shown among rabbits hopping around in his room. The advertisement text stated this boy too had Pompe disease, but was opposed to using rabbits. Even a non medical professional with knowledge on Pompe disease could see in a moment, this boy absolutely didn’t have Pompe disease. Pompe patients in the Netherlands were upset by this attack and the VSN decided to appeal at the regulatory authority to forbid this type of incorrect advertisement over the backs of Pompe patients. The director of the VSN, Marcel Timmen, and I went together and we won the case by far. The commercial and the advertisements were forbidden per direct.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com1tag:blogger.com,1999:blog-5208562407788722307.post-58817006937733045052010-01-31T19:51:00.001+00:002010-01-31T23:01:59.049+00:00Maryze's story - Part 3In February 1997 my brother, Onard, returned from his 6 month exchange program at Trinity<br />
College in Dublin, Ireland. To hear the latest developments in Pompe disease,<br />
he came with us to the patient meeting of VSN. At that meeting I introduced him<br />
to Dr. Arnold Reuser. They talked and a little while later Onard applied for a<br />
training opportunity at the Department of Clinical Genetics of the Erasmus<br />
Medical Center in Rotterdam. He worked there from March 1997 till March 1998<br />
and participated actively in the research in Pompe knock out mice and the<br />
effect of enzyme replacement therapy derived from genetic modified rabbits.<br />
<br />
He was not allowed to tell us anything, but my father always asked him if the sun<br />
was shining in Rotterdam or if it was cloudy. Often the answer was that it was<br />
shining. Later we heard from Dr. Arnold Reuser that it was sometimes tough, as<br />
some mice got into an anaphylactic shock during the treatment with<br />
alpha-glucosidase. This was a serious adverse effect, and then it is even more<br />
serious when it concerns a disease your sister is suffering from. Luckily these<br />
adverse effects could be managed well (<a href="http://www.blogger.com/goog_1264967051176">Human Molecular Genetics, 1999, Vol. 8,</a><br />
<a href="http://hmg.oxfordjournals.org/cgi/content/full/8/12/2145">No. 12 2145-2153</a>).<br />
<br />
<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjfZ5D9tGhfQ_KOUg0VE_5VR60PjCfkuhcbB6uTfmu3g4hR5GbZr8UFm7G48hpOCZ2JWsKQEkFr3nIe6moM4y2u2brCuowvCtXyC56bENZAkzma156zKKxPC8mJCNbTfhCCw8iUY5wjjdc/s1600-h/maryze3.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjfZ5D9tGhfQ_KOUg0VE_5VR60PjCfkuhcbB6uTfmu3g4hR5GbZr8UFm7G48hpOCZ2JWsKQEkFr3nIe6moM4y2u2brCuowvCtXyC56bENZAkzma156zKKxPC8mJCNbTfhCCw8iUY5wjjdc/s400/maryze3.jpg" width="400" /></a> </div><div class="separator" style="clear: both; text-align: center;"><i>Thesis of Dr Anges Bijvoet, with a contribution from my brother, Onard Schoneveld. </i></div>Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-24321374671945742822010-01-31T19:44:00.001+00:002010-01-31T23:01:18.820+00:00Maryze's story - Part 2In the morning of the 14<sup>th</sup> of November 1996 I was still in bed and felt not that well. My parents were at work and Anton too was busy with a project. I was thinking about what to do, while at the same time I couldn’t do much physical activity as my body had deteriorated. Walking was very difficult and also breathing became such an effort that I often just sat on my bed or desk using the ventilator.<br />
<br />
That morning I turned on the radio while laying still in my bed. The news was on an I heard a male voice saying: ‘A dutch biotechnological company had announced to develop a treatment for a rare disease. It would be the first time ever in human history that genetically modified rabbits were used to produce a medicine’. I was somehow shocked and felt awake right away. I sat still in my bed awaiting for the next bulletin to be sure. Then again it was said, but this news reporter added one little important detail: He mentioned it was about Pompe disease. I somehow still couldn’t believe it and walked to the living room to turn on the television and to watch video text. There it was in black and white: Pompe disease, treatment, rabbits.<br />
<br />
I called my father and Anton. They too heard this news and were like me excited, but also with a bit of restriction as this news was so overwhelming that we couldn’t fully understand it yet. This was what my brother told me about. Then the phone rang and a Pompe patient I knew very well, asked if I heard the news. We talked about it and she was like me very excited. We promised eachother to keep eachother informed. I dressed myself and kept listening to the radio that continued bringing the news out. Then I was called again. It was Ysbrand Poortman of the VSN who had attended the press conference in Geel, Belgium, where Pharming had a small pilot plant to produce the enzyme. Ysbrand Poortman too asked me if I was informed about the latest developments and I told him that I indeed was. He told me he was approached by the Dutch News Broadcasting Service (NOS) and they wanted to interview a Pompe patient. ‘Are you interested?’, he asked. I said yes, without understanding the impact of this answer.<br />
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<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgmMGwtO9nOSi7bDtiUHKTjCdopt40ChxJlDMuB0z9_zxb3SYkE6VYQ6NBxkeG_JA7ui_j8FUOOS2J4io9B7XDjeqlGn5SbvrcHf036mWbu-lwnj3XeEmKiJkkahyqEiyGLUK8pbJCe9hg/s1600-h/maryze2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgmMGwtO9nOSi7bDtiUHKTjCdopt40ChxJlDMuB0z9_zxb3SYkE6VYQ6NBxkeG_JA7ui_j8FUOOS2J4io9B7XDjeqlGn5SbvrcHf036mWbu-lwnj3XeEmKiJkkahyqEiyGLUK8pbJCe9hg/s400/maryze2.jpg" width="347" /></a></div><div style="text-align: center;"><i>Articles in the international media on Pompe diseaseand its upcoming treatment derived from genetically modified rabbits.</i> </div><br />
One and a half hour later the camera crew and reporter were at my home. Luckily my sister and a good friend of hers also were home from school already, so they had tidied up my room a bit. Three hours later the news item on Pompe disease, treatment with rabbit milk and Pharming was on prime time news in the Netherlands. This was my first television appearance and many more would follow on broadcastings in the Netherlands, Germany, Belgium, BBC world and of course interviews with magazines and newspapers in The Netherlands, Germany, Belgium, Norway and Finland. Pompe disease was brought into the world.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-78503435771152016902010-01-31T19:26:00.010+00:002010-02-06T16:43:59.511+00:00Maryze's story - Part 1<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOQEOhkc0sJpaxyG5ps7wrOhTyer-Z3PuYurVQE6bGVw9SQLyJDcKvd7CEhflZksYCw-WKpeOxcjLDzBvrmW4e2IHfaAKIOzSHchZjoNSR9PE3Oyb9GJqzi6cFGEE8wDrt4n9j5A7pw6o/s1600-h/maryze.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOQEOhkc0sJpaxyG5ps7wrOhTyer-Z3PuYurVQE6bGVw9SQLyJDcKvd7CEhflZksYCw-WKpeOxcjLDzBvrmW4e2IHfaAKIOzSHchZjoNSR9PE3Oyb9GJqzi6cFGEE8wDrt4n9j5A7pw6o/s400/maryze.jpg" width="296" /></a> </div><div class="separator" style="clear: both; text-align: center;"><span style="font-size: x-small;"><i>Maryze at the IPA Founding Conference, 1999</i></span></div><div class="separator" style="clear: both; text-align: center;"> </div>This is my contribution to the Pompe disease blog that Kevin O’Donnell created. I will first introduce myself. I am Maryze Schoneveld van der Linde and I was diagnosed with Pompe disease in 1979 when I was 8 years old.<br />
<br />
My parents immediately became member of the Dutch Association for Neuromuscular Diseases (VSN). Around 1985 diagnosis groups were established within the VSN, so that patients with a specific disease could meet and also learn about the latest developments in their disease. My mother became part of the Pompe group and remained active for many years. In 2008, she would finally receive a royal decoration for her voluntary work all those years.<br />
<br />
During one of the meetings of the diagnosis group, Wil de Geus, a woman with Pompe disease told the group that it was good to talk about good care for Pompe patients, but she didn’t only want care, but also a cure…afterall no one wants to have Pompe disease and a treatment was much wanted. The group members agreed and they got in touch with the scientists and physicians with knowledge on Pompe disease. These scientists and physicians were Dr. Christa Loonen, Dr. Arnold Reuser and Ans van der Ploeg. They were invited at our annual patient meeting and it was during one of those meetings I met Ans van der Ploeg for the first time.<br />
<br />
She was young and working on her PhD on Pompe disease. I must have been 16 years at that time. I really admired her for what she did. Doing research on my disease and trying to understand what exactly is going on. Dr. Loonen too always was present on those meetings and always was interested in the person behind the patient. She is still a regular guest at our meetings even years after her retirement. After all we were not only patients, but also people with a life. One year later, in 1987, at another annual patient meeting Dr. Reuser asked me if I was interested to write with a woman with Pompe disease in Australia. This lady has asked him about the latest developments in his laboratory and also asked him if he knew some other Pompe patient to exchange experience and knowledge. I agreed to write to her, though I wasn’t that skilled in English at that time. Though so I thought, it is a good way to learn English.<br />
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From that moment on Linda Zaidan and I exchanged letters for over a couple of years, until internet made email and chatting possible. Linda was a couple of years older than me and at the moment of writing less affected than I. Unfortunately that changed…she soon became also dependent on a ventilator and she deteriorated quickly. From her I learned that an enlarged tongue and the inability to speak well or even to smile was not only a symptom in children with the infantile onset form, but also in adults with a very severe progressive form of Pompe disease. In 1987 Anton and I met at a youth club and one year later when I was 18 we started our relationship. He knew about my disease, but decided that we could do it together. When we met I was still able to ride a bike and able to walk, but I too deteriorated.<br />
<br />
In 1990, at the 2nd year of my study cultural anthropology at the University in Leiden, I was admitted to the ICU at the Utrecht Medical Centre to be put on ventilation. I was there for 5 days to get all the settings right and to receive optimal ventilation. After the weekend I went to my classes again, as I did have to prepare for some examinations. 3 years later my first wheelchair entered my life. <br />
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In 1993 my brother started his study Molecular Biology at the same University of Leiden. In 1995 I remember that he once came home and told my parents and me about exciting news he heard during class. He said that a teacher had told about this rare neuromuscular disease, that no one ever heard about, Pompe disease and that they were working on a very new biotechnological method to get a treatment for that disease. He told the students about their creation of transgenic rabbit that were genetically modified in such a way that the females produced the enzyme human alpha-glucosidase in their milk. The theory was that this enzyme, when purified, could be given to humans with Pompe disease.<br />
<br />
My brother of course was excited and went to this teacher after class. He said: ‘Well you said that no one knows about Pompe disease, but I do. My sister does have this disease’. The teacher, Martin Verbeet, was very surprised that one of his students had a sister with this rare disease they were doing research for with the newest technologies available. He told my brother everything he knew. From that moment I had hope, though I also continued with my life knowing that people were at least working on my disease and that only 100 meters from where I lived in my students house in Leiden. Who could ever thought about that? If it was pictured in a movie, you wouldn’t believe it.<br />
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<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpH7KJ4Dvq0jlK8QxvAzdA83uz7JQaeY9R7kr1V5esB9cmrM3J1JECE481x6T6POpqHLHnfPcp1imESUibtsmliIPoF2RwgiLSv1AkUTj5uhyTKzqDbmiW2NfAhcuIHm4uN8G5URSZKa8/s1600-h/maryze1.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpH7KJ4Dvq0jlK8QxvAzdA83uz7JQaeY9R7kr1V5esB9cmrM3J1JECE481x6T6POpqHLHnfPcp1imESUibtsmliIPoF2RwgiLSv1AkUTj5uhyTKzqDbmiW2NfAhcuIHm4uN8G5URSZKa8/s400/maryze1.jpg" width="275" /></a></div><br />
<div style="text-align: center;"><span style="font-size: x-small;"><i>Receiving my Masters degree in Cultural Anthropology at the University of Leiden, June 19 1995</i></span></div><br />
In 1995 I graduated with a masters degree in cultural anthropology and went back to live with my parents in Varsseveld. My body had deteriorated so that I knew I couldn’t live alone. In spite of my physical problems I decided that my life would be as normal as possible, so I did apply for a job at several companies. Not long after I was invited for a job of 4 hours per week to work as a community worker with Turkish women close to where I live. It was exactly what I liked and was able to handle.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com1tag:blogger.com,1999:blog-5208562407788722307.post-69610519755748304472010-01-21T22:04:00.001+00:002010-01-31T22:59:34.380+00:00The Fate of the Transgenic Patients - Tiffany House<b>The Fate of the Transgenic Patients . . .</b><br />
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After Novazyme and Genzyme merged and Pharming went into receivership there was one looming question on the minds of those of us involved in the transgenic trials: what was going to happen to the patients?<br />
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As Kevin has already mentioned, when the decision was made to pursue the CHO method in lieu of the transgenic, the patients and the patient organizations were assured that treatment for the transgenic patients would continue until they could be transitioned to the CHO product–or indefinitely if transition was impossible. <br />
<br />
However, shortly after Pharming went into receivership in August 2001 this tune changed. Instead, we were told that the transgenic patients were Pharming’s responsibility—NOT Genzyme’s. As you can imagine, this declaration was met with opposition from the international patient community and from the “team” in the Netherlands.**<br />
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The international Pompe community banded together and stood up to Genzyme. We said that this was not acceptable, and we held them accountable. At the end of the day (and after many “conversations”), Genzyme stepped up to the plate and accepted that the transgenic patients were their responsibility. BUT, there were still more “battles” to come.<br />
<br />
While Genzyme agreed to continue treating the transgenic patients by transitioning them to CHO (the offer of indefinite treatment if transition from the transgenic enzyme was impossible was now off the table), they declared that the Duke product was more effective than the transgenic, and the doses of these patients was to be reduced to 5/mg/kg/week. To put this into perspective, at that time the patients in the transgenic infantile trial were receiving 40mg/kg/week and those in the juvenile trial were receiving 20/mg/kg/week. Ultimately, after many discussions, the transition<br />
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I can’t speak to all that was said behind closed doors during this time. What I can say is there was a genuine concern regarding the transition and how patients would do. The team in the Netherlands wanted more information to make sure it was safe to transition their patients. But, the ability to wait for this information was taken out of their hands by upcoming events . . . <br />
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The transgenic method of production had been foregone in favor of the CHO method of production, so the production of the transgenic product ceased (and the fate of rabbit herd remains a mystery). That meant that there was a limited amount of supply left. The transition could only be delayed for as long as the supply held out. Then things got more complicated: a decision was made by the Pompe Leadership Team at Genzyme to begin using a new brand of vials, and the vials started to break. The breaking vials meant that the need to transition was sped up. There was no more time to make sure the transition would be smooth and not have adverse consequences for the patients.<br />
<br />
By summer of 2003 most of the transgenic patients had been, or were in the process of, transitioning to the Duke product. The next hurdle that had to be faced was the dose. Within 6 months it was clear that the lower dose was not effective–patients were deteriorating where as before they had been improving. After many conversations Genzyme finally agreed to increase the dose (a further increase was later agreed to) and by summer 2004 the transgenic patients were once again receiving the same dose they had received while on transgenic (see my story on the Patients page of the AMDA website for an account of how I deteriorated during this time).<br />
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Unfortunately, by that time severe damage had been done to some patients. I personally remember seeing and talking to one of the patients in the original infantile trial. After a year and a half on treatment this patient was able to be off of the ventilator for several hours a day and could move her arms a little. These were drastic improvements. When the dust had settled after the transition, she was no longer able to be off of the ventilator and her condition had drastically declined. I can’t help but wonder what her life would be like today if her dose had not been reduced.<br />
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**I say “team” because if you ever talk to Drs. van der Ploeg or Reuser they will never take credit for the things they have accomplished—instead, they say it was the “team” that did it. This is, to me, just one of many of the examples of what drives them and their work. For the Dutch “team” it is not about notoriety or recognition. They have spent decades researching and working on Pompe for the sake of science. But, more importantly, for the sake of the patients the science will help.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com1tag:blogger.com,1999:blog-5208562407788722307.post-62860065327911357832010-01-21T22:00:00.002+00:002010-02-06T16:42:26.986+00:00The 2001 AMDA conference - Tiffany House<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLuXvYVD6zEg_P27GCo6fRSw5sUbrYYI_7_jlQSkDciN03uYmwBkbQVmNbUpZDWbWSe4pVwbA2AyfUgL75rUgbuCwmDekU79Jepgk940EgHj82kRXXz4aZu7byJftbTrCKj3LcUPOr33E/s1600-h/amdaconf.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="266" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLuXvYVD6zEg_P27GCo6fRSw5sUbrYYI_7_jlQSkDciN03uYmwBkbQVmNbUpZDWbWSe4pVwbA2AyfUgL75rUgbuCwmDekU79Jepgk940EgHj82kRXXz4aZu7byJftbTrCKj3LcUPOr33E/s400/amdaconf.jpg" width="400" /></a> </div><div class="separator" style="clear: both; text-align: center;"><span style="font-size: x-small;"><i>L to R: The late Jose Valentin and friend, The Houses</i></span></div><div class="separator" style="clear: both; text-align: center;"><br />
</div>As Kevin has already related, the weeks leading up to the 2001 AMDA Patient Conference were filled with turmoil and uncertainty. <br />
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I suppose the best place to start is, as always, at the beginning. The conference was the culmination of nearly a year of planning and organizing. By early September everything was planned and we were ready to go–eager to host the first ever Pompe patient meeting in the United States. It was going to be the first time that there was a conference for Pompe patients, and devoted <i>only</i> to Pompe disease—and from the responses we had gotten patients were planning to turn out en-mass.<br />
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Then, the tragedy of 9/11. As you will probably all remember, this was a time of turmoil and uncertainty in our country. BUT, despite statements made by Novazyme/Genzyme the AMDA never waivered in our decision to hold the conference. Kevin has already mentioned the statement posted to the GSDnet by Julie Smith of Genzyme on behalf of John Crowley (Novazyme) and Jan van Heek (Genzyme)—can you imagine our shock when we opened that email? We swiftly, and firmly, responded by saying that the conference was NOT cancelled and that we were still expecting a very good turnout from the scientific community. The exact message that was posted is as follows:<br />
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<blockquote>Dear All,<br />
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Thank you for your response. It was a complete shock to us to check our emails and find that the AMDA conference had been cancelled. We are flabbergasted that these two companies have taken it upon themselves to decide when and where a patient conference should be held.<br />
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We want to go ahead with the meeting. We have confirmations from keynote investigators that they will definitely present information to the patients at the meeting. These dedicated scientists/physicians are truly friends of the patients and have the patients' best interests at heart. The patients have a right to gather, exchange information, and to be informed about results from the ongoing trials. They also have the right to question the corporations about timelines and patient criteria for participation in new trials.<br />
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If we let Novazyme/Genzyme dictate all phases of what patients and patient organizations have a right to know and do, then we become putty in the hands of these "CORPORATE GIANTS".<br />
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We have all been affected by the bombings in the US, and we certainly understand anyone's apprehension with boarding an airplane. But if the corporations wanted to come--there are other means of travel available in the US. They can make other arrangements as are many of the patients. Many patients have told us that they want this meeting to take place and that they want to come to this meeting in spite of many obstacles; health, travel delays, etc. If patients have this much determination, then Novazyme/ Genzyme should be willing to come also to address this gathering.<br />
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Until Novazyme/Genzyme's announcement, we had 150 participants. As recently as Friday, both of these corporations had 20 people registered to attend.<br />
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Are there other motives for not wanting to attend????? <br />
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Novazyme and Genzyme stated that they were the sole sponsors of the AMDA Patient Conference. THIS IS NOT TRUE! AMDA has funded 2/3 of the conference. Genzyme has funded 1/3 of the conference. Novazyme has contributed nothing.<br />
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The following institutions were contacted today by AMDA and have vowed their support. They will make presentations at the conference.<br />
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Duke University-presentation on the CHO Trial<br />
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Rotterdam--presentation on the Transgenic Trial<br />
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Germany--presentation on the CHO trial and the Transgenic Trial<br />
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Presentation by the FDA--approval process for orphan drug products<br />
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Australia--presentation on diagnostics<br />
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UK--presentation on patient advocacy<br />
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Patient--presentation by a patient in a current clinical trial for Pompe's Disease<br />
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Marylyn House<br />
AMDA</blockquote><br />
Kevin has spoken as to the possible motivations for “cancelling” our conference, but you would have to ask those who made the decision to know for sure. What I do know is, despite the lingering concerns caused by 9/11 the patients and scientific community demonstrated their strength and perseverance and showed up on the first day of the conference. My mom (Marylyn House) remembers talking to Dr. Reuser and thanking him for attending. He replied that his wife said he should come–it was too important not to. I share that anecdote because I think it is important to realize that it is not just the scientists, themselves, who are dedicated to our disease — it is their families, too. <br />
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That leads us to the conference itself. There were some really great presentations. What I remember most were the presentations by Duke (made by Dr. Amalfitano) and Erasmus (made by Dr. van der Ploeg). In particular, I remember the slides showing how the infants did on the different treatments (CHO vs. transgenic). What struck me the most about these slides was that both doctors presented slides that had graphs of the progress of the patients on therapy. The Duke slide showed three patients that showed an impressive improvement. However, after this initial improvement 2 of the 3 patients (or lines) sharply dropped off and then stabilized. As I recall, the decline was to baseline (or slightly below). In contrast, the slide from Erasmus showed steady improvement for all patients–albeit different degrees of improvement (one patient had a pretty drastic improvement while another had a very slight improvement).<br />
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You may think that I am biased as I was on the transgenic product–but I’m not. What I am talking about is interpreting a black and white graph of how the patients did. I am by no means trying to degrade the accomplishments of the Duke team–the babies were alive which they would not have been without treatment. All I am saying is that, to me, it was very apparent that patients on the transgenic enzyme seemed to do better.<br />
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I remember talking to Dr. Amalfitano after his presentation about my feelings. I can’t recall his exact words but they were along the lines of: “who are we to say that stabilization isn’t good.” He’s right. I firmly believe that in a disease like Pompe the first goal that needs to be reached is stabilization. Anything else is a bonus. But, at the time, I was having a hard time reconciling the graphs I saw with Genzyme’s decision to pursue the CHO method instead of the transgenic.<br />
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Now that I am older and wiser ;-) I understand that CHO was the quickest way to bring treatment to Pompe patients around the world. Personally, though, I wouldn’t be surprised if the transgenic product rears its head again one day in the future . . .Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-63238530488091579092010-01-21T21:50:00.001+00:002010-01-31T22:57:11.257+00:00A break from our normal scheduleOne of the things I really hoped to do with this blog was to include the perspectives of other members of the international Pompe community. I am therefore delighted to say that I now have a number of contributions that I will be posting to the blog. I to begin with I have contributions from Tiffany House (of the AMDA and IPA) and Maryze Schoneveld van der Linde (of the VSN and IPA). Both people with stories to tell and who were (and are) in a good position to observe events. I thank them both for their excellent contributions and encourage others to contribute their own.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-3236980325266551852010-01-20T23:48:00.001+00:002010-01-31T22:56:19.460+00:002002 concluded - last thoughts on John CrowleyI described 2002 as the John Crowley era. In fact, it was the only time that John was directly involved in the Pompe project. As far as I can judge, he did a competent job and left a more patient-centred approach that continues at Genzyme to this day. That is his real professional achievement, I think, and it's not a bad legacy to leave. It's one he should be proud of.<br />
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However, was John responsible for the development of a treatment for Pompe disease, as <i>The Cure</i> implies and <i>Extraordinary Measures</i> more-than-implies? No, absolutely not.<br />
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John Crowley is, I believe, a good man and a good father. He is one of the worldwide Pompe family. He has a prodigious talent. However, for me, <i>The Cure</i> is the story of a talent wasted. The story of Novazyme, in particular, is essentially the story of a gigantic displacement activity. It's what kept John busy while the rest of the world got on with developing a treatment for Pompe disease.<br />
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I can't help but wonder what might have been. What if John had been more of a team player and that amazing energy and talent had been used within the international Pompe community? What might have been achieved then? Looking through my notes in writing this blog, I saw that John Crowley was originally down to attend the IPA founding conference in 1999 but did not come. What if he had? What might we all have achieved then? What if...?<br />
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I'm glad - beyond glad in fact - that John's children were finally able to take part in a trial of ERT. As I've said before, my heart sings every time I hear of a child or adult I know of starting treatment. And I'm glad that he and his wife have had the courage to tell the story of what it is like to cope with seriously ill children. That makes <i>The Cure</i> a moving book at times and, by all accounts, <i>Extraordinary Measures</i> a moving film. It's a story that many parents coping with seriously ill children will identify with and one that deserves to be more widely known and understood. It's a great thing that they have helped raise awareness in this way. I just wish that they would tell the real story of the development of a treatment for Pompe disease too.<br />
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Pretty soon - already, in fact - new Pompe patients will simply accept that the treatment is there and not give much thought to how it came about. That's as it should be, I guess. However if <i>The Cure</i> and <i>Extraordinary Measures</i> fill the vacuum, then a great disservice will have been done to the researchers who really did help develop the treatment and to the international patient community who played a part in it. That's why <i>The Cure</i> is, ultimately, a disappointing book. It's a shame, because with a bit more competent research - and, perhaps, a bit more generosity of spirit - it could have been a <i>great</i> book. Another 'what if...?' <br />
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That's why it's important that the real story is written down, so that it is not forgotten and is there for those who do want to know. One day, that story will be told by the great book that it deserves - until then, this rather sloppily written blog will have to do. But I digress.*<br />
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<span style="font-size: x-small;">*Proving my point about sloppy writing. See what I did there?</span>Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com1tag:blogger.com,1999:blog-5208562407788722307.post-62947380405483740252010-01-20T23:02:00.001+00:002010-01-31T22:55:36.182+00:002002 - the IPA patient registryAside from the continuing development of ERT, the IPA was involved in another important project , starting in 2002. This was the establishment of a Patient Registry as Erasmus University, Rotterdam. <br />
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Looking ahead to clinical trials with late onset patients, it was acknowledged that the 'natural history' of pompe disease in adults was poorly documented. This meant that, for example, it would be more difficult to show a positive effect of ERT, because there was no baseline to compare patients against. Arnold Reuser and Ans van der Ploeg came up with the innovative idea of a <a href="http://www.pompecenter.nl/en/?Pompe_Survey">Patient Survey</a>. This would consist of a professionally authored questionnaire to be completed by patients with the anonymised data held at Erasmus University, to be analysed and published. The IPA helped fund the work and ensured that patients themselves had some ownership of their own data. The survey has led to a number of publications, with researcher Marloes Hagemans as the lead author (listed at the link above) - a very valuable contribution to our understanding of Pompe disease.<br />
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Yet another ground-breaking success story from the <a href="http://www.pompecenter.nl/en/?Home">Rotterdam team</a> - and another example of the patient community taking control of their own destiny.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-47198167183925601972010-01-20T22:41:00.001+00:002010-01-31T22:54:53.022+00:002002 - continued2002 continued the established pattern of regular liaison between Genzyme and the IPA.<br />
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Where possible, there were public reports of these meetings. For example, the visit of the IPA Executive to Genzyme HQ, on 16/17 April 2002 led to a positive <a href="http://worldpompe.org/index.php/news/article/396/">joint statement</a>. This was followed by accounts of the teleconference in <a href="http://worldpompe.org/index.php/news/article/395/">September 2002</a> and a further update in <a href="http://worldpompe.org/index.php/news/article/394/">December 2002</a>. Of course, these were only the public face of continuous contacts at various levels.<br />
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On of the main decisions, early in 2002, was to progress to commercialisation using Genzyme's own in-house enzyme, priduced using their own cell line. We were therefore in the position where the eventual product was not that used in either the first clinical trial in Rotterdam or the second trial at Duke University. Of course, the actual enzyme was very similar - what changed was simply the method of production. After all, insulin used today is not produced in the same way as that used in Banting and Best's Nobel Prize-winning work on developing a treatment for diabetes. It doesn't lessen their achievement one bit. Likewise, the fact that Genzyme now produce alpha-glucosidase in their own cell line does not detract one iota from the ground-breaking achievements of the pioneering Rotterdam team, or the following trial at Duke. <br />
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Genzyme agreed that the clinical trial patients should continue to receive the enzyme they received in the trial (Pharming for Rotterdam, Synpac for Duke) until an orderly transition could be arranged. It's fair to say that this was the cause of a great deal of discussion and concern. Patients who had done well, particularly with the Pharming enzyme, were - understandably - apprehensive about switching to another product. A particular issue was the fact that the Pharming enzyme was given at a higher dosage and it was felt that a benefit was lost on transfer to the lower dosage Genzyme product. Some of those directly involved may care to comment here.<br />
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Genzyme continued to make progress with production, bringing more bioreactors on stream. 2002 progressed according to plan, with a series of further trials being announced in November 2002. At the same time, it was announced that John Crowley would be leaving Genzyme. There's a little more about this in The Cure but essentially he had not been able to separate his personal and professional situations. I don't blame him for that - I don't think there's anyone in the world who could have done so. His replacement was Frank Ollington, who I would credit as being the person who brought the project to fruition. Frank's attitude was - I paraphrase wildly - "I don't give a rat's ass if you <i>like</i> me - my job is to make this product <i>happen</i>." And he did.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com0tag:blogger.com,1999:blog-5208562407788722307.post-38445568395421177912010-01-17T23:14:00.001+00:002010-01-31T22:53:25.937+00:002002 - The John Crowley eraReading through the huge number of emails, tele-conference transcripts and written notes from 2002, I find it hard to reconcile them with the account of this year in The Cure.<br />
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In fact, I think that the account in The Cure, in its rush to airbrush the patient community out of the picture, sells John Crowley short somewhat.<br />
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In general, I do think that John succeeded in bringing some of the Novazyme philosophy to Genzyme. In a lengthy transcript from 26 February 2002, of a teleconference between John Crowley, Jan van Heek and the IPA Board, I am struck by the new-found openness shown by Genzyme. They went into great detail about their plans - information that was in confidence and commercially sensitive. Regulatory-sensitive too. There was a lot of trust, openness and good humour. Something had changed for the better and was going right. I, for one, am happy to give John Crowley the credit for that.<br />
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The exciting news was that good progress had been made with manufacturing. By the end of 2002, supply of enzyme was no longer expected to be a bottleneck, opening the way to larger trials.<br />
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This new positive relationship (a complete change-around from the nadir of September 2001) was cemented by a visit of the IPA Board to Genzyme's HQ near Boston, in April 2002.<br />
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We were back on track.Kevin O'Donnellhttp://www.blogger.com/profile/00826027508838686684noreply@blogger.com1