Selected Accomplishments

Tay-Sachs Disease

• First enzyme replacement trial that demonstrated that this neurodegenerative disorder of infancy is not amenable to enzyme replacement therapy, and therefore, efforts need to focus on prevention.
• Delineation of the clinical and biochemical features of the adult-onset form of Tay-Sachs disease.
• One of the first Tay-Sachs Prevention Programs in which Jewish couples are screened to determine if they are at risk for having affected babies.
• Development of new and improved enzyme assays for Tay-Sachs screening.
• Establishment of the Chevra Dor Yeshurim Program in the Hasidic community to prevent engagements between carriers of certain Jewish genetic diseases. To date, over 120,000 young Hasidic students have been screened, and over 340 proposed "matches" have been avoided. Expansion of the program to Israel and other centers in North America was established with Mount Sinai collaborators.
• The first to establish DNA-based testing for Tay-Sachs as a routine adjunct to the enzyme-based testing.
• Organization of an international Symposium on Tay-Sachs disease, which will be documented in a book with chapters by the world's experts.

Gaucher Disease

• Established first comprehensive Gaucher Disease clinics for the diagnosis and management of patients and their families. Determined natural history and variability of disease.
• Established first (and only) Gaucher Disease Patient Support Group, which has met regularly at Mount Sinai since 1984.
• Developed improved methods of patient diagnosis and carrier identification by enzyme assay.
• Purified and characterized the enzyme (b-glucosidase) from normal and affected individuals and demonstrated unique abnormalities of the defective enzyme. Performed and evaluated novel therapeutic endeavors including plasmapheresis and successful bone marrow transplantation.
• First to determine chromosomal location of the Gaucher gene.
• First to sequence the Gaucher enzyme and identify critical regions of function (active site domain).
• First to identify and characterize certain common gene mutations causing Gaucher disease.
• DNA analysis of Gaucher patients facilitated first genotype-phenotype correlations, thereby improving prognosis and counseling.
• First and only Center to offer DNA-based screening for Gaucher disease; first Gaucher Disease Prevention Program.
• First Center to establish a Gaucher Disease Treatment Center for Enzyme Replacement Therapy.
• First to conduct FDA-required clinical trials of recombinant enzyme for the treatment of Gaucher disease.
• Organized first international Symposium on Gaucher Disease at Mount Sinai and edited first (and only) book on this disease with contributions from 40 of the world's experts.

Niemann-Pick Disease

• Established the first Niemann-Pick disease diagnosis and evaluation clinic at Mount Sinai.
• First to isolate and characterize the normal gene (acid sphingomyelinase) that is defective in Niemann-Pick disease.
• First to map the Niemann-Pick gene to human chromosome 11.
• First to identify mutations causing Niemann-Pick disease. Specific mutations caused either Type A (a severe infantile neurodegenerative disorder) or Type B (a milder disease without neurologic involvement), thereby providing the molecular basis for these different clinical entities. To date, over 12 different Type A or B mutations identified, have included three common defects causing Niemann-Pick disease in the Ashkenazi Jewish population.
• First to produce the normal enzyme using recombinant DNA techniques. This enzyme will be used for future clinical trials of replacement therapy.
• First to perform gene therapy in Niemann-Pick cells. The introduction of the normal gene into cultured cells from Niemann-Pick patients corrected the enzymatic defect and normalized the cells. This accomplishment provides the first rationale for the development of gene therapy to cure Type B Niemann-Pick disease.

Familial Dysautonomia

• First to perform prenatal diagnosis using linked genetic markers.

Crohn's Disease

• Used positional cloning techniques to narrow the localization of the predisposing genes.