History
The disease is named after Johann Pompe, who characterized it in 1932. Pompe described accumulation of glycogen in muscle tissue in some cases of a previously unknown disorder. This accumulation was difficult to explain as the enzymes involved in the usual metabolism of glucose and glycogen were all present and functioning.
The basis for the disease remained a puzzle until Christian de Duve's discovery of lysosomes in 1955 for which he won the Nobel Prize in 1974. His co-worker Henri G. Hers realised in 1965 that the deficiency of a lysosomal enzyme (alpha glucosidase) for the breakdown of glycogen could explain the symptoms of Pompe disease. This discovery led to establishing the concept of lysosomal storage diseases, of which 49 have been described (to date).
Despite recognizing the basis for the disease treatment proved difficult. Administration of the enzyme lead to its uptake by the liver and not the muscle cells where it is needed. In the early 1990s two Dutch scientists, Arnold Reuser and Ans van der Ploeg a PhD student using alpha-glucosidase containing phosphorylated mannose residues purified from bovine testes, they were able to show that an increase in the enzyme's activity in the normal mouse muscles.
Later in 1998, Dr. Yuan-Tsong Chen and colleagues at Duke University (陳垣崇,Dr. Chen is currently the director of the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.), using the enzyme produced in Chinese Hamster Ovary cells demonstrated for the first time that the enzyme can clear the glycogen and improved the muscle function in Pompe disease quail. The results of the work at Duke were impressive with one treated bird recovering to the point of being able to fly again.
This was followed by production of clinical grade alpha-glucosidase in Chinese hamster ovary (CHO) cells and in the milk of transgenic rabbits. This work eventually culminated in the start of clinical trials with the first clinical trial including 4 babies receiving enzyme from rabbit milk at Erasmus MC Sophia Children’s Hospital and 3 babies receiving enzyme grown in CHO cells at Duke University in 1999.
The currently approved Myozyme is manufactured by Genzyme Corp. in Cambridge, Massachusetts, USA. Its development was a complex process. Genzyme first partnered with Pharming Group NV who had managed to produce acid alpha-glucosidase from the milk of transgentic rabbits. They also partnered with a second group based at Duke University using Chinese hamster ovary cells. In 2001, it acquired Novazyme which was also working on this enzyme. Genzyme also had its own product (Myozyme) grown in CHO cells under development. In November 2001, Genzyme chief executive Henri Termeer organised a systematic comparison of the various potential drugs in a mouse model of Pompe disease. It was found that Duke enzyme was the most efficacious, followed by Myozyme. However, due to easier manufacture of Myozyme, work on the other products was then discontinued.
Funding for research in this field was in part provided by Muscular Dystrophy Association and Acid Maltase Deficiency Association in USA and the Association of Glycogen Storage Disorders in UK and the International Pompe Association.
John Crowley became involved in the fund-raising efforts in 1998 after two of his children were diagnosed with Pompe's. He joined the company Novazyme in 1999, which was working on enzyme replacement treatment for Pompe's. Novazyme was sold to Genzyme in 2001 for over US$100 million. The 2010 film Extraordinary Measures is based on Crowley's search for a cure.
Read more about this topic: Glycogen Storage Disease Type II
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