Ceramide, which mediates stress-induced apoptosis, is generated from sphingomyelin in a reaction catalyzed by acid sphingomyelinase (ASMase). Antagonists of ASMase, which prevent generation of ceramide and thereby prevent stress-induced apoptosis, can be used to protect the ovary from the apoptotic cell death otherwise induced by chemotherapy, radiotherapy or the effects of aging.
Drs. Richard N. Kolesnick and Jonathan L. Tilly have demonstrated that administration of lysophospholipids that antagonize ASMase function, including sphingolipids and, more specifically, sphingosine 1-phosphate (S1P) and S1P analogs, protects the female germline from normal aging as well as from the premature failure resulting from cancer therapy regimens, including chemotherapy or radiotherapy. Administration of a composition containing S1P or an S1P analog provides a new approach to the preservation of ovarian function and could be useful in preventing infertility in female cancer patients, in preventing or ameliorating menopausal syndromes, and in improving in vitro fertilization techniques.
There are no similar therapies presently available.
Proof of concept established in mice
Richard Kolesnick, MD, Laboratory Head, Molecular Pharmacology & Chemistry Program, Sloan Kettering Institute, Memorial Sloan Kettering