Research

The GDF is run by volunteers, which enables us to put all fundraising dollars directly towards fighting genetic diseases. Since its inception, the Foundation has granted millions of dollars to support genetic and genomic research at the Icahn School of Medicine at Mount Sinai, which has led to a number of breakthroughs, including:

  • The identification of 25 genes that cause genetic diseases, where either the defect or the cause had previously been unknown
  • The identification of a susceptibility gene for prostate cancer
  • The identification of a gene for a major form of congenital heart disease, a form of arthritis and a form of bone disease is leading to a drug therapy for osteoporosis
  • Gene mappings for four debilitating syndromes including Tukel Syndrome, a congenital eye disease that leads to blindness
  • The identification of genes for four other syndromes including Hereditary Osteosarcoma Syndrome
  • Identification of key DNA lesions for diseases involving Cancer, Immunodeficiency, and severe birth defects

And from Mount Sinai’s gene research has come treatments:

  • Treatment for Fabry Disease, FDA approved in 2003
  • Investigational treatment for Niemann-Pick Type B Disease, in Phase 2 trials
  • Testing a new concept for treatment of Genetic Diseases at the National Institutes of Health

Each rare disease breakthrough opens doors for knowledge that can help cure myriad other diseases.

GDF ENDOWED CHAIR – FRANCIS CRICK PROFESSOR OF HUMAN GENETICS

The Chair was awarded  to Edward H. Schuchman, PhD, Vice Chairman for Research, Department of Genetics and Genomic Sciences at Mount Sinai, in 2003.  For more than 25 years, Dr. Schuchman has studied the biology of Lysosomal Storage Disorders (LSDs), a group of more than 50 rare genetic diseases. Some highlights of Dr. Schuchman’s research, which has resulted in significant scientific advancements in the prevention, diagnosis and treatment of LSDs, are below.

Niemann-Pick disease (NPD): NPD Types A and B are severe, progressive degenerative conditions that are often fatal for children. There are no approved treatments. Dr. Schuchman and Dr. Robert Desnick, Dean for Genetics and Genomic Medicine at Mount Sinai, were the first to isolate the gene encoding the enzyme linked to NPD (acid sphingomyelinase or ASM) and to use this gene to manufacture a recombinant form of the enzyme that could be used for therapy. They also discovered the genetic mutations that cause NPD Types A and B and a method to screen for them. NPD is now included in Jewish Genetic Disease screening panels throughout the world and there are plans to extend screening methods to other at-risk populations.

Dr. Schuchman further created the first animal model for NPD and used it to develop a potential Enzyme Replacement Therapy (ERT). A Phase 1b clinical trial with the Genzyme Corporation evaluating the safety and tolerability of the compound rhASM in adults with NPD Type B was recently completed and an international Phase II trial is being planned. Mount Sinai is continuing to help identify NPD patients, who will have the opportunity to access the investigational therapy and contribute to a better understanding of the disease. With DNA sequencing, approximately 30 new NPD patients are now diagnosed at Mount Sinai each year, and Dr. Schuchman’s lab has performed gene analysis studies on more than 1,000 patients from over 30 countries.

Dr. Schuchman also has pioneered the development of brain-directed gene and stem cell therapy using the mouse model of NPD. Most recently (2014), he and his collaborators in Spain published on a new pharmacological approach to slow/prevent neurological progression in NPD mice.

Farber Disease: Farber disease is a progressive disorder often characterized by debilitating physical and neurological health effects, especially painful swelling of the joints and lung disease. Death usually occurs in the first decade, and there are no approved treatments. Dr. Schuchman and his team were the first to isolate the gene encoding the enzyme linked to Farber Disease (acid ceramidase or AC), and to use this gene to manufacture the missing enzyme. They discovered the genetic mutations that cause Farber Disease, constructed the first animal model, and are developing several new mouse models. They are using these animal models to develop new therapies.

In 2013, Dr. Schuchman co-founded Plexcera Therapeutics LLC, which received exclusive license from Mount Sinai Innovation Partners to commercially develop a form of AC to treat diseases caused by AC deficiency, which include Farber’s Disease and other more common disorders such as Cystic Fibrosis.

Broader Applications: Dr. Schuchman’s lab continues to work closely on the roles of ASM and AC in the regulation of cell survival and function, and to understand how the enzymes and genes are involved in various other disease pathologies that include type 2 diabetes and several types of cancer.

Mucopolysaccharidoses (MPS):  Dr. Schuchman has been studying a group of 11 LSDs known as the mucopolysaccharidoses for his entire career. These disorders are characterized by severe and debilitating skeletal deformities, and together with his colleague, Dr. Calogera Simonaro, they have uncovered a common inflammatory mechanism leading to these skeletal defects. Based on this research, they have also “re-purposed” an existing drug, pentosan polysulfate (PPS), for the treatment of MPS. A first clinical trial evaluating PPS in MPS patients will begin in 2014.

Dr. Schuchman is committed to understanding the causes of LSDs and developing new treatments that will improve the health and quality-of-life of patients suffering from genetic diseases.