We are very pleased to provide this update on progress toward devising methods to silence the SPTLC1 gene as a potential therapy for HSAN1. We have made progress in three areas. The key point is that we have now developed two types of reagents that can silence the SPTLC1 gene. One type of reagent is composed of small strings of ~ 20 molecules of nucleic acids (antisense oligonucleotides or ASO’s) that have sequences complementary to specific sequences in the SPTLC1 gene. The concept is that these ASO’s bind RNA from the target gene and thereby activate enzymes that break-up the RNA, preventing it from making protein. As we have reported before, we have been fortunate to have Havisha Karnam as a graduate student working in conjunction with Anastasia Khvorova Ph.D. on this project. Dr. Khvorova is an internationally recognized expert in the chemistry of ASO’s. With Dr. Khvorova’s guidance, Havisha has used two types of chemistry (designated LNA gapmers and hsiRNA) to generate ASO’s that can silence SPTLC1. In particular, she has developed ASO’s that specifically target hamster SPTLC1 and not mouse, and reciprocally. She also now has ASO’s that target human