The first IPA Conference was held on July 2-4, 1999, in Naarden, the Netherlands. The meeting was attended by over 60 participants from 11 countries which included members of the medical and scientific community, patient organizations and industry. Presentations included a historical overview of Pompe’s disease, ongoing research in enzyme replacement and gene therapy, and presentations from patient organizations. Randall H. House, president of AMDA (USA), chaired the first day’s proceedings. Y.S. Poortman, president of VSN (the Netherlands) opened the conference and welcomed the guests.
The opening presentation was given by Dr. M.C.B. Loonen. Dr. Loonen served as Head of the Child Neurology Department of the Academic Hospital Rotterdam, the Netherlands, from 1971 until retirement in 1995. Her thesis entitled, “The variability of Pompe’s Disease. A clinical, biochemical and genetic study of glycogen storage disease type 2, or acid maltase deficiency”, appeared in 1979.
Dr. Loonen’s presentation gave a historical overview of Pompe’s disease from it’s initial description by J.C. Pompe, a Dutch pathologist in 1932; the discovery of lysosomes in 1955 by Christian de Duve (et al); the discovery by H. G. Hers (et al) that glycogen storage was caused by the deficiency of the lysosomal enzyme, acid alpha-glucosidase and his unsuccessful attempt at enzyme replacement therapy in 1963; the 1964 demonstration by Baudhuin (et al) which showed that glycogen stored in the liver of Pompe patients was present mainly within the lysosomes. In 1965 it was recognized that there are also “late-onset” forms of Pompe’s disease.
Although presently retired, Dr. Loonen is still involved in the clinical trials for enzyme replacement therapy currently underway at Sophia Children’s Hospital in Rotterdam.
Dr. M.G.E.M. Ausems, Clinical Geneticist and Head of Genetic Counseling in the Department of Medical Genetics, University Medical Center Utrecht, the Netherlands, based her presentation on her publication “The frequency of Glycogen Storage Disease type II in the Netherlands; implications for diagnosis and genetic counseling.” (Ausems MEM, Verbiest J. Herman MMP, it al; Eur J Hum Genet in press).
Since 1995 she has been involved in studies on the frequency of Pompe’s disease and genotype-phenotype correlations of the disease in close collaboration with Dr. Reuser, Dr. van der Ploeg and Prof. Dr. J.H.H. Wokkel, Department of Neurology, University Medical Center Utrecht, the Netherlands.
Dr. Ausems’s data predicts that frequency of GSD II is 1 in 40,000 in the Dutch population as opposed to the frequently quoted figure of 1 in 100,000. A recent study on the carrier frequency by Frank Martiniuk, Ph.D., New York University Medical Center (USA), also indicated a disease frequency of 1 in 40,000, based on his study of the general population in New York (Martiniuk F, Chen A, Mack A et al. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. AM J Med Genet 1998; 79:69-72.)
Dr. Ausems concluded, “Our results suggest that the world wide frequency of GSD II must be higher than 1 in 100,000 and that the birth prevalence of adult GSD II is two times higher than that of infantile GSD II.
Prof. Dr. John J. Hopwood, Deputy Head of the Chemical Pathology Services and Head of the Lysosomal Disease Research Unit, Women’s and Children’s Hospital, North Adelaide, South Australia, stressed the importance of joining together all LSD, lysosomal storage disorders (of which there are 40), to broaden the patient base and thereby, bring this category of disorders to the foreground. Based on his research he has found that LSD affects approximately 1 in 5,000.
For over 20 years Dr. Hopwood’s research has been linked to the provision of a diagnostic service and the development of therapy for patients with LSD. Specifically toward GSD II he stated, “We have been developing new methodology to achieve fast, inexpensive and non-invasive procedures for the early detection and diagnosis of GSD II in individuals from newborns to adult populations,” but he went on to say that diagnosis of GSD II using blood samples is complicated by the presence of other alpha-glucosidase activities.
Arnold J.J. Reuser, Ph.D., Associate Professor of Cell Biology, Department of Clinical Genetics, Erasmus University Rotterdam, the Netherlands, also made a historical presentation on Pompe’s disease.
Dr. Reuser has been involved in Pompe research since 1973. Throughout the 80s and 90s, he was involved in the biosynthesis and structure of acid alpha-glucosidase, the cloning of the acid alpha-glucosidase gene, mutation analysis, and the development of a mouse model for Pompe’s disease. All of these endeavors have lead to the commencement of clinical trials in enzyme replacement therapy for Pompe’s disease currently in progress at Sophia Children’s Hospital in Rotterdam.
Dr. Reuser joined Professor Hans Buller, director of Sophia Children’s Hospital Rotterdam, and Dr. Ans van der Ploeg, principal investigator, who recently expressed their optimism about the progress of the trial.
Dr. Reuser concluded by “…….highlighting the role of the patients, patient organizations and charities that have kept the ‘process’ alive. Our research team…….has experienced tremendous support…….from patients…….(and) patient organizations and charities (such as), the AGSD (UK), the AMDA (USA), the Prinses Beatrix Fonds and the Sophia Foundation, in particular, …….(who) have made financial contributions to keep us going.” He closed his speech by commending the formation of the IPA.
Dr. Andrea Amalfitano, Duke University Medical Center (USA) made a presentation entitled “Therapy for GSD-II; Enzyme based therapeutics and novel gene therapy approaches.”
(see research from Duke June 25, 1999 & Aug. 3, 1999)
Dr. A.T. van der Ploeg, Sophia Children’s Hospital Rotterdam, The Netherlands, gave her presentation entitled “Enzyme therapy for Pompe’s disease” on the last day of the conference.
see Phase II Juvenile Trials Underway in Netherlands, July 4, 1999
Presentations were also made by industry representatives:
“A Transgenic Approach to Enzyme Replacement Therapy in Pompe Patients” was jointly made by A. Vos, Ph.D., Pharming/Genzyme LLC (Netherlands); J. Dalle, MSc, Pharming NV (Belgium); A. Curtis, MBA, Genzyme Corp (USA).
“The Challenges of rhGAA Manufacture ” was the title of the presentation made by Blythe Devlin,Ph.D., Synpac (N.C.) Inc.
Patient organization presentations included the following:
“Knowledge is power” and “The importance of good information,” Kevin O’Donnell, Ph.D., AGSD (UK);
“Forming a national Pompe group, our experience,” Marylyn House, AMDA (USA);
“The International Pompe Association, position, objectives, policy and activities,” Ysbrand Poortman, VSN (Netherlands); “Developments in the area of Pompe’s disease,” Haske van Veenendal, VSN (Netherlands);
“Funding treatment before the government subsidy approvals,” Robert Morrison, MDA (Australia);
“Legal procedures regarding the International Pompe Association,” Helmut Erny, SHG Glycogenose Deutschland eV(Germany)
Maryze Schoneveld van der Linde, representative of VSN, presented a moving autobiographical portrait of a Pompe patient’s endurance of this progressive debilitating disease. Maryze has struggled with the juvenile form of the disease for over 20 years. She was diagnosed with the disease at the age of 8. Her speech was entitled “From patient initiative to treatment.”
Ria Broekgaarden, VSN, and Randall House, AMDA, co-chaired the second day’s events. Thomas Schaller, SHG Glykogenose Deutschland (Germany) chaired the final day’s session.
A closed session to formulate and discuss IPA objectives was co-chaired by Randall House and Ysbrand Poortman and included only members of patient groups. Mr. House summarized the committee report at the general meeting on the final day.