Substrate Reduction Therapy for Smith-Lemli-Opitz Syndrome and Related Disorders

Smith-Lemli-Opitz Syndrome (SLOS) is a rare autosomal recessive genetic disorder affecting the final step of cholesterol biosynthesis. SLOS is characterized by slow growth before and after birth, mental retardation, and multiple congenital disabilities. There is no FDA approved treatment for SLOS. Patients may benefit moderately from palliative care through an increase in dietary cholesterol to compensate for the endogenous block in cholesterol biosynthesis. However, dietary change offers only limited clinical benefit in mental improvement because the level of cholesterol or 7-DHC in the cerebrospinal fluid is not significantly improved. 

Researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) are studying inhibitors of sphingolipid biosynthesis as a potential therapeutic for treating SLOS and related disorders. This substrate reduction therapy technology may include a compound, a method, a pharmaceutical composition, and an agent. The patents include claims for the use of nojirimycin derivatives to treat SLOS and diseases with a secondary Niemann-Pick type C disease like cellular phenotype. Of specific interest is the therapeutic use of N-butyldeoxynojirimycin (miglustat, available in FDA approved form as Zavesca®).

This technology is a part of the ongoing clinical program related to SLOS and is currently available for co-development or licensing.