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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Tuesday, 7 April 2009

Christian de Duve, Henri-Gery Hers and serendipity

"In the field of observation, chance favours only the prepared mind"
Louis Pasteur
J C Pompe had described a disease which had the symptom of glycogen accumulation, particularly in the heart, due to an 'inborn error of metabolism'. In the years that followed, further research on glycogen metabolism made the cause of the disease more mysterious, rather than less.


Gerty and Carl Cori were pioneers in this field and discovered the missing enzyme in von Gierke's disease. Indeed, they won a joint Nobel Prize for their work on glycogen metabolism. In 1957, G T Cori listed what are now known as glycogen storage disease types 1-4. Only in the case of Pompe disease was the missing enzyme unknown. The key to solving the puzzle of what caused Pompe disease lay in a seemingly unrelated discovery taking place elsewhere.












US stamp issued in honour of Gerty Cori (the formula is wrong, unfortunately...)

In 1955 Christian de Duve and co-workers were investigating the effect of insulin on the liver, when they came across some odd results, in the shape of some intra-cellular particles which seemed to have digestive properties. Intrigued, they stopped their work on insulin and investigated this phenomenon. de Duve named these particles lysosomes and so began a long period of research by his group and others. This was an important discovery. The idea that cells themselves had compartments (now known as organelles) with particular functions was now firmly established. Thus was the idea of the lysosome as the 'recycling plant' of the cell established. Prof de Duve was awarded the Nobel Prize for his discoveries in 1974.

I wrote to Professor de Duve a few years ago, asking him if it had ocurred to him that his discovery of lysosomes might have some medical significance. He replied that it had not - it was curiousity-driven 'blue skies' research. However that connection was made by one of his original co-workers, Henri-Gery Hers.

After the discovery of lysosomes, most of de Duve's team joined him in this exciting direction, however Henri-Gery Hers retained his interest in carbohydrate metabolism and founded his own research group instead. This ultimately led him to become involved in research on glycogen metabolism. Following the death of Gerty Cori, he decided to take up her research on identifying the missing enzymes responsible for the glycogen storage diseases.

In the course of this he examined samples from patients from around the world, including some with Pompe disease. This confirmed the puzzle that in pompe disease all of the known enzymes for the metabolism of glycogen were present and correct - yet there was still massive accumulation of glycogen.

That was still not his main line of research. Hers was trying to develop a test for the enzyme responsible for glycogen storage disease type 3. Unfortunately, his test turned out to be for an enzyme that was at normal levels in his GSD 3 samples. Fortunately, by chance, he had included some Pompe samples in his experiment - and his test showed a deficiency in all of those cases. He had discovered the enzyme deficiency responsible for Pompe disease.

That wasn't all though. Hers knew that his new enzyme, an alpha-glucosidase, worked best at an acid pH. This set him thinking about his previous work on lysosomes which had an acid environment - could this new enzyme be situated there? He went on to establish that it was. He further deduced that the normal function of this enzyme was to break down glycogen inside the lysosomes and that, in its absence, glycogen would accumulate, as it was isolated from the normal enzymes for glycogen metabolism found in the rest of the cell. In 1965 he established the concept of lysosomal storage diseases, based on his Pompe disease research.

All in all, a remarkable piece of scientific detective work. Yes, there was an element of serendipity involved, however Hers was quick to realise the significance of what he found. Truly chance favours only the prepared mind.

Thanks to de Duve and Hers, the cause of Pompe disease was now known over 3o years after its discovery. The next task was to find a way to treat it - that would take an equally long time.

1 comment:

  1. I've just now come across Kevin's carefully researched 'history' of Pompe Disease. What a fine accomplishment! I will eagerly read to the last post, confident that though the story has not yet ended, it will eventually have a happy ending.

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