First International Symposium on Niemann-Pick C

FIRST INTERNATIONAL SYMPOSIUM
on NIEMANN-PICK C

An International Workshop

The Niemann-Pick C Lesion and
The Role Of Intracellular Lipid Sorting In Human Disease

October 14-17, 1999

Campus of the National Institutes of Health
Washington, D.C. USA

Sponsored By:
National Institutes of Health
Ara Parseghian Medical Research Foundation
National Niemann-Pick Disease Foundation
Niemann-Pick Disease Group (U.K.)
Niemann-Pick Selbsthilfegruppe e. v.
Bristol Myers Squibb
the Cezar Fernandes family

Organizing Committee:
Dr. Peter G. Pentchev, NIH
Dr. Marc Patterson, Mayo Clinic
Dr. Stephen Sturley, Columbia University
Dr. William Pavan, NIH

The following report was submitted in October, 1999, by Eunice Eversdyk, Director-at-Large of the NNPDF, who attended the Symposium. Eunice and her husband, Marion, have 5 children, two of whom are afflicted with NPC. Their daughter, Cindy, died in February, 1991, at the age of 34 from NPC. Dennis Eversdyk, also an NPC patient, lives with Eunice and Marion in Abilene, Texas. He is 45 years old.

The International Workshop for NP-C research was held at the Natcher Center on the National Institutes of Health campus with the Bethesda Marriott serving as residential headquarters for the participants. The conference was financially supported by the National Institutes of Health, the Ara Parseghian Medical Research Foundation, the U.K. Niemann-Pick Disease Group, the German Niemann-Pick Self Support Group, and the NNPDF with additional support from the pharmaceutical industry and private families.

The goal of this three-day workshop was to bring together scientists from widely ranging and relevant areas of research related to NP-C. Speakers were encouraged to reveal and discuss recent unpublished findings. The invited speaker lists consisted of renowned scientists in the fields of metabolic disorders, metabolic modeling, genetics, and cellular biology. Posters, displayed in the foyer, were available for everyone to view.

Dr. Peter Pentchev opened the conference, followed by a representative from each of the four NPC foundations speaking on behalf of their family and all the affected families. Jim Green, "The U.K. Niemann-Pick Disease Group"; Hunt Ozmer, "The National Niemann-Pick Disease Foundation"; Cindy Parseghian, "The Ara Parseghian Medical Research Foundation"; and Edmund Fabianski, "The German Niemann-Pick Self Support Group". Slides were shared by the speakers so scientists could see, as well as hear, the pain shared by NPC families.

Presentations were given from 8:30AM-5:30PM each day with a morning, lunch, and afternoon break. The first day emphasized the disease phenotypes, chaired by Dr. Marc Patterson, Mayo Clinic, describing the latest advances in understanding of the neuropathological profile, the phenotypic similarities which unify or distinguish Niemann-Pick disease, and the latest diagnostic procedures. Also included were perspectives of how other syndromes may reflect sterol trafficking disorders. In the afternoon Dr. Laura Liscum chaired an overview of the current status of cellular cholesterol processing and the NP-C lesion. Friday focused on molecular genetics of Niemann-Pick C, chaired by Dr. Stephen Sturley, Columbia University, with overviews of the structural and functional characteristics of the NPC1 genes with insights from orthologs and homologs. Dr. Karan Snow, Mayo Clinic, chaired an afternoon discussion of mutational analyses in Niemann-Pick C Disease. Saturday was a view on cellular characterization of the NPC1, chaired by Dr. Yiannis Ioannou, Mount Sinai Medical School, on the latest scenarios regarding the subcellular localization of the NPC1 protein and ensuing ramifications that may suggest how this disease is manifested. Dr. Shutish Patel, New England Biomedical Research Center, CT, chaired the afternoon discussion concerning how the disease is most profoundly and predominantly a neurodegenerative disorder. The afternoon chairs were Dr. Richard Gregg, Bristol Myers Squibb, and Dr. Laura Liscum, Tufts University, who looked toward therapeutic strategies. The final session of the conference focused on the scope of the NP-C challenge and the prospects for therapeutic interventions. At the conclusion of each speech, questions from the scientists in the audience were encouraged.

A special keynote lecture by Dr. Francis Collins, Director of the National Human Genome Research Institute, NIH, was one of the hightlights of the conference. He spoke on "Human Genomics and the Future of Medicine." This project is expected to be completed the first part of next year. There are five large centers working on the project, as well as another 10 centers with smaller assignments. When completed this will only be the end of the beginning, followed by DNA sequencing, medical training, variation of genes, understanding gene functioning, etc. Dr. Collins gave a view of the effect the genome project will have on medicine over the next 40-year period relating to longevity of 90 years, illness detected by molecular surveillance, genome based health care, gene therapy labs created for most diseases, and genetic prevention of disease. Dr. Collins expects results of the project will be published around December, 1999.

It is agreed that NP-C is an incrediibly complex disease. It is hoped scientists will share their knowledge to find a cure for the disease. It was amazing to hear of the different avenues of research and how many scientists world-wide are working on the problems associated with NP-C.

A hospitality party for participatnts was held Friday night, sponsored by the NP Foundations.

On the final evening of the conference a farewell dinner for the participants and their guests was held at the Pier 7 Restaurant on the waterfront in Washington, D.C. Again, representatives Jim Green, Cindy Parseghian, and Jerry Blixt, from three NP-C foundations made a short presentation thanking all the researchers for their efforts. A gift from the foundations was presented to Dr. Peter Pentchev (NIH) in appreciation for all his years of scientific research on NP-C. Everyone expressed their gratitude to him, to Dr. Roscoe Brady, and Dr. Marc Patterson. Dr. Brady (NINDS, NIH) responded with a humorous speech and recognized Dr. Pentchev's work. Dr. Patterson paid tribute to all the researchers and families.

On the trip back to the hotel in Bethesda, buses toured through the Nation's Capital allowing participants to see the major scenic attractions of the city.

The very successful meeting concluded Sunday morning with an early morning buffet at Betheseda Marriott and informal discussions dealing with the next NP-C conference and other concerns.

This ends Eunice's official report but she added some personal notes which she agreed that the webmasters could publish:

One presentation showed slides of litter mate kittens, one affected with induced NP-C. [This] one would keep falling over while trying to play with a ball. On affected felines there was no liver failure. There was osteoporosis prior to [the feline becoming] non-ambulatory. Low cholesterol diets in cats showed no neurological differences. Tried a bone marrow transplant from a litter mate; the cat had later symptoms but became non-ambulatory a the same age.

NP-C is wrong lipids, wrong place, wrong time. Sleep disorders [are] recognized in NP-C patients but not studied. NP-C is present in fetal life. EVERY cell abnormal from birth, including colon, stomach, heart, muscle, brain, kidney, liver, adrenal, lung, carcass, peripheral, etc. Neurofiber tangles in the brain found constantly in slowly progressive NP-C (not found in mouse model) like in alzheimers.

There is a wide diversity of mutation in NP-C; 26 mutations of the gene in the U.S.; 24 in France, 13 in Canada; 10 in Portugal.

Dr. Collins said their have been over 100 trials over 10 years in replacing the cystic fibrosis gene with delivery to cell not working yet.

NP-C brain is getting atrophic with progressive disease process. Working on drugs to prevent buidup of cholesterol or to stimulate movement of it out of cells.

During a break we learned of a 50-year-old man who had a pleen removed and was NP-C with NO symptoms at all. Still has none. It is a crazy disease.

The Official NIH Symposium Website contains abstracts of all conference presentations: http://www.nhgri.nih.gov/CONF/Niemann_Pick