Robert H. Brown, Jr, DPhil, MD, University of Massachusetts
We have had some significant forward momentum in our HSAN1 work. Havisha Karnam has generated a series of chemically modified anti-sense oligonucleotides (small pieces of DNA or RNA that block the production of proteins in the cell) that very clearly suppress expression of SPTLC1 in vitro (in a culture dish). We now have assays pending to ascertain if, as we predict, this also silences expression of the deoxysphingoid bases (backbone of sphingolipids).
In a parallel project, we have generated microRNA that silence expression of the SPTLC1 gene in cells, also in vitro. We are now almost completed packaging this in an adenoassociated virus (AAV) for testing in the HSAN1 mice. We hope to be infusing the mice with the AAV containing the microRNA to silence SPT by the end of June. This has taken longer to get up and running than we anticipated but should nonetheless be accomplished shortly. This is the work of Gaby Toro and Nick Wightman.
A post-doc in the lab, who works on microRNA biology, formerly studied aspects of serine palmitoyltransferase inhibition, ceramide levels and pathology in Alzheimer’s Disease. This individual, Hirosha Geekiyanage, has worked with our