Dr J C Pompe

Dr J C Pompe
Discoverer of Pompe disease

About this blog

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

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

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

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

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Sunday 20 December 2009

The 3rd AMDA conference - December 1998

As the IPA had been formed, albeit with an interim committee, the patient community was on a more solid footing. Therefore  Ysbrand Poortman and I were invited to attend the 3rd AMDA conference with took place in Bethesda, Maryland on December 3-5 1998. This was at the HQ of the US National Institutes of Health and Paul Plotz of the NIH had a hand in putting the programme together, along with Arnold Reuser, Gerben Moolhuizen and Randall House.

When I was invited in July, I was naturally thrilled at the thought of a front row seat at such a gathering. People who I had corresponded with by email, or who only knew as names from scientific papers - fantastic! However, as December approached, it became clear that I was also going to have to give a talk. What on earth would I say to such an audience and would they even be interested?

The programme was everything I had hoped for. There was a session on animal models, which included not only a reprise of the quail work but also reports of the development of different strains of 'knockout' mice (mice genetically engineered to have the alpha-glucosidase gene removed, so that they showed Pompe symptoms) by Arnold Reuser and Nina Raben.

Rochelle Hisrchhorn, a Pompe research veteran, chaired a  session on 'molecular and metabolic aspects' which included a talk by someone I had not previously heard of, called William Canfield. He had a unique take on ERT. I've previously described how the Dutch team showed that previous ERT attempts had failed because the enzyme used lacked mannose-6-phosphate residues, which would have allowed them to be targeted on the lysosomes. Consequently, the forthcoming ERT trials would use enzyme with those residues on them. However Dr Canfield reckoned that these would fail because they didn't have enough residues. The greater the number of residues, the more enzyme would end up in the lysosomes.

I wasn't convinced by this. The Dutch work had shown that enzyme levels could be increased beyond the point where clinical symptoms occurred. Wouldn't that be enough? And enzymes are, after all, a catalyst; adding them in excess doesn't necessarily mean that you have more reactions taking place (in this case, more glycogen breaking down). It didn't make sense to me and talking with the scientists there afterwards, it didn't wash its face with them either. So I soon forgot about it. Like did I realise what a spectacular and costly waste of time that presentation would turn out to be.

The other sessions were of more immediate interest. two sessions on gene therapy, which looked very much like the long-term solution. Gene therapy would entail replacing the faulty gene in patients so that they could make their own enzyme, rather than need ERT.  There were good talks from such luminaries as Barry Byrne, Paul Kessler and Andy Amalfitano.

However, the main event was the human trials session chaired by Arnold Reuser. This featured a real guest star turn, Roscoe Brady, the pioneer of ERT for Gaucher disease, as well as Ans van der Ploeg, who described the Phase II clinical trial for Pompe disease.

This would consist of two groups. Firstly, a small group of infants. The reasoning was obvious - these were the most severely affected and the clinical outcome was well characterised and devastating. Any effect of ERT would therefore be obvious. There would also be a second group with the 'juvenile' type. These would be older children who would be able to respond to a wider range of tests and also answer the questions put to them during the trial. It seemed obvious that this was the best way forward to ensure as rapid a demonstration of the effectiveness of ERT as possible.

On the final day, Nina Raben and Rochelle Hirschhorn spoke about mutations and population incidences. Hannerieke van der Hout spoke on the need for a formal patient database. Ansd then it was my turn to speak.

I'd given my paper the snappy title Translating science into English: the role of patient organisations and the internet in helping patients to become intelligent customers. I gave some of my own back ground and then what was essentially an argument in favour of scientists engaging with patients, through the medium of patient organisations. I had been looking for something to finish with and it had finally come to me. I recalled a quote from rabbi Hugo Gryn, a UK Jewish leader whose distinctive gravelly voice was a regular feature of radio discussion programmes. He had a saying which I related: "You can live for 3 weeks without food and 3 days without water - but you cannot live for 3 minutes without hope."  Then I ended my talk with: "We look forward to ERT becoming a reality. However, all of you in this room, every one of you who has worked on Pompe's for all of those years,  brought us something very important: hope. On behalf of the patient community, I thank you all from the bottom of my heart for what you have done."

I meant it then and I mean it now.

The finale was an impressive presentation by Randall and Marylyn on the work of the AMDA.- an organisation which many of those present had, of course, directly benefited from.  In my view, this conference, exciting enough in itself, marked a further evolution of the relationship between scientists and patients. From now on, we were all on the same team.

The full programme, list of participants and summary is available online.

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