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. 

Potential Commercial Applications: Competitive Advantages:
  • A therapy for Smith-Lemli-Opitz Syndrome (SLOS) and other diseases which has a secondary Niemann-Pick type C disease like cellular phenotype
  • Potentially first-to-market in a disease with no treatment option
  • Therapeutic option rather than palliative care

Development Stage:
Discovery (Lead Identification)


Forbes Porter (NICHD)  ➽ more inventions...

Frances Platt (University of Oxford) ()  ➽ more inventions...

Emyr Lloyd-Evans (University of Oxford) ()  ➽ more inventions...

Intellectual Property:
U.S. Pat: 8,557,844 issued 2013-10-15
U.S. Pat: 9,428,541 issued 2016-08-30
Australia Pat: 2008269585 issued 2015-07-02

Platt, F. et al. Disorders of cholesterol metabolism and their unanticipated convergent mechanisms of disease.  PMID 25184529

Collaboration Opportunity:

Licensing only

Licensing Contact:
John Hewes, Ph.D.
Phone: 240-276-5515

OTT Reference No: E-206-2007
Updated: Mar 20, 2020