We have been fortunate to recruit a new doctoral student, Huiya Yang, to join us in studying HSAN1 here at UMass. She is an outstanding molecular biologist who will work with me to generate two new models of HSAN1 in mice. The new mouse models will be knock-in instead of transgenic mice. That is to say, we will replace one of the two mouse SPTLC1 normal genes with the gene bearing a mutation. Then, using those models, will work on strategies to silence the offending genes. Huiya brings lengthy preliminary experience to the project, having worked extensively on suppressing other types of disease genes in mouse models of other neurological disorders.
Two developments in the field are noteworthy over the last year. First, it is now well established that the same gene defects that trigger HSAN1 can also cause a form of macular degeneration, characterized by unusual vascular changes in the retina. For this reason, we are setting up a collaboration to evaluate the retina of our existing, transgenic HSAN1 mice. It is possible that this will provide a sensitive, early readout of pathology in the mice. In turn, such a readout may facilitate testing of therapies.
The second development of interest is that it has been discovered that a set of mutations in the HSAN1 gene (called SPTLC1) that do not cause HSAN1 can nonetheless cause a form of early childhood Lou Gehrig’s disease. This is not directly related to HSAN1 but nonetheless holds enormous interest as it provides further insight into the central importance of SPTLC1 as a determinant of normal neuronal development and function.
These developments heighten and intensify the level of interest in the biology of HSAN1. We look forward to working closely with the Deater Foundation on these and related topics over the coming year and are deeply grateful for its support. Hopefully, we will be able to work with the Deater Foundation to assemble another consortium meeting in early 2020. That will provide an excellent venue to draw these research themes together and plan our next steps forward.