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, 6 January 2010

Oxford 2000 part 1

Every year I say the Pompe's workshop was the biggest and best so far, and this year's was no exception. Just under 50 people attended the workshop,held on Saturday 9 September 2000 at the Oxford Belfry Hotel.

As well as UK patients and families, we also had participants from Denmark,The Netherlands, Germany and the USA. These included some representatives from Genzyme and  Pharming, of whom more later.

To begin with, we had the star of the show - Ans van der 
Ploeg. She was accompanied by Arnold Reuser, Marian
Kroos and Hannerieke van den Hout. Yes,we had the cream
of Pompe's research attending the one little meeting. I can't
tell you how pleasing it was to see not only the research
leaders but also Marian Kroos, whose name has co-authored
many research papers and has been Arnold Reuser's
collaborator for many years, and Hannerieke van den Hout,
who has been deeply involved in the clinical trial and is the
'first author' on the Lancet paper.

I introduced the proceedings by mentioning the change in
attitude towards enzyme replacement therapy for Pompe's,
from it being effectively a dead duck to a successful
clinical trial. I pointed out that this was due to the work
carried out in the Netherlands, in large part by people
present today.

Dr van der Ploeg gave a good account of the ERT trial
on infants. She began by saying that she had said in every
talk for the last 10 years that enzyme replacement therapy
was a possibility. Now, for the first time, she could
present real evidence of it working.

She presented the results of 36 weeks of treatment for
the 4 infants. The inclusion criteria were: showing
symptoms of Pompe's, including heart enlargement; less
than 10 months of age; alpha-glucosidase deficiency;
muscle biopsy diagnosis.

The ages at diagnosis were 1, 4, 0.5 and 6 months, and
at inclusion, 3, 7,2.5 and 8 months.

Patients 2 and 4 had lost a great deal of muscle function
and required oxygen.

After 12 weeks, all 4 babies had an alpha glucosidase
activity within the 'normal' (i.e. non-Pompe's) range.

Muscle biopsies (images shown) illustrated that glycogen
storage had been markedly reduced. Heart size was
also reduced.

Muscle function showed improvement. One child is still on
a ventilator and one is now walking.


The treatment is generally well-tolerated.

The treatment prolongs life.

Therapeutic effects were observed.

Muscle function and cardio-respiratory function were both

And perhaps most importantly - it is easier to prevent than
to cure, therefore treatment should be started early.



Q: The dose was increased 3-fold during the trial. Are
you satisfied with the current dose?

A: Yes. Enzyme activity is normalised, which is a good
sign that the dose is correct.

Q: Is it possible that not all muscle activity would be

A: Yes, it is possible - some muscle fibres may be
beyond repair. Recovery may be a very long process
for severely affected patients.

Q: Did any patients show an antibody response to
the enzyme?

A: Yes but this did not appear to have an effect on
the treatment.

Q: Does enzyme get to the lysosomes?

A: Yes - we know this because glycogen is removed
from the lysosomes by the enzyme.

Q: Is it possible that measuring enzyme activity may
overstate the amount there, since you may be measuring
enzyme that is in the rest of the cell too?

A: Theoretically this is possible, however alpha
glucosidase is only active at the acid pH of the lysosomes,
not the neutral pH of the rest of the cell. In the end, the
best measure of enzyme activity is that the glycogen is
removed and muscle function improves. This has been
shown by the trial.

Q: What the implications for the late onset types?

A: Too early to say but treatment holds promise. It will
be a long process but hopeful for the future for ALL
Pompe's patients.

Q: Can you say anything about the status of juvenile trials?

A: The trial has started but it will take longer than with the
infants to make certain that measurements and improvements
are actually due to the treatment. There is a need to gather
reliable statistics and data.

Q: Is a controlled diet more important in the later onset forms?

A: There are many hypotheses. It is certainly very important
to have enough protein for muscles. Keeping busy/moving
is a good way to help muscle strength.

[Prolonged applause]

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