Dr J C Pompe

Dr J C Pompe
Discoverer of Pompe disease

About this blog

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

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

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

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

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Wednesday, 22 August 2012

The Duke response

In the 9 August  advance online publication section of Genetics in Medicine, two letters appear . One is from Arnold Reuser  Inconsistent reporting about dosing, dosing regimen, and immunomodulation therapy in Pompe disease and a response from Andy Amalfitano, Priya Kishnani and YT Chen: Response to Reuser.

Once again, these are behind a paywall but let me precis.

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 et al 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.

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.

Unfortunately, it does not. Here is what it says.

Dr Reuser is correct in noting that in our original report,
we had not disclosed that in latter portions of the first clinical
trial for patients 1 and 2 (who had declining AIMS scores and
increasing antibody titers), that we attempted to treat these
patients with increased doses of the enzyme,...

Going on to explain that:

These attempts were ongoing during submission and review of our original
manuscript, and were well beyond the scope of that manuscript,
requiring further more detailed review and reporting as noted in subsequent publications
And finally concluding that their statement
“Three patients with
infantile Pompe disease have been receiving twice-weekly
intravenous infusions of rhGAA for 14 to 17 months,”
 Might be better changed to:
Three patients with infantile Pompe disease have been receiving
at least twice-weekly intravenous infusions of rhGAA for
14–17 months
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.

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.

Secondly, there is that section in the 2001 Duke paper still uncorrected:

Similar cardiac improvements in four infants treated with rhGAA from rabbit milk for 9 months have recently been reported15; 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.
 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.

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