Ongoing HSAN1 Research

Dr. Robert H. Brown, Jr. University of Massachusetts Medical

Recent work in the Brown Lab has focused on two aspects of HSAN1. One addresses therapy directly, the other indirectly through production of new mouse models. The first line of work, done by an outstanding graduate student, Huiya Yang, has been to suppress expression of one of the key mutant genes that causes HSAN1 – the long chain sub-unit of the serine palmitoyl transferase enzyme (SPTLC1). The underlying concept is that the mutant protein exerts a toxic effect on neurons by forming of a set of toxins, deoxysphingoid bases (DSBs). We believe that reducing the level of the mutant SPTLC1 gene will reduce levels of DSBs and slow or stop the neuropathy. We are exploring two approaches to gene silencing of DSBs. One project targets RNA using a class of compounds known as microRNA. This work has been co-mentored by an outstanding senior faculty member, Dr. Guangping Gao, who directs the Gene Therapy Center at UMass Medical School. Another targets RNA using anti-sense oligonucleotides (ASO); the ASO project has benefitted enormously from collaboration with Dr. Jonathan Watts, a faculty member in the RNA biology unit at UMass Medical. Dr. Yang has

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