[chenja]

I am a big believer in the prion-like spread hypothesis which seems to be a common thread for neurodegenerative disease, and led a study (in press) that supports this idea in Alzheimer's disease and frontotemporal dementia. Once there is a critical mass, I think it would be challenging to slow the progression of the disease, which may speak to the importance of early treatment. However, given the proven genetic risk factors for these diseases (Mendelian forms, GWAS hits) - which are related to things like UPR, microglia activation, etc - I think that there is a possibility to slow the progression of disease. We also feel the same way you do about the repositioning angle, but it is a nice way to try to get something safe to patients that can potentially be proven quickly and cheaply in a small Phase 2 trial.

In terms of the expression data for diseases, we are doing a systemic review and re-analysis of publically available raw micoarray data from GEO, as well as RNA-sequencing and microarray data that we will publish soon and make publically available. That part is what I mentioned in the video; rather than just looking for differentially expressed genes (which is what most of the associated studies have done), we use network methods we developed to identify what we think are the key drivers of disease. Also, by combining data we get more power to find signal. To match these with drugs, we use a combination of proprietary gene expression data as well as data from large public projects.

Thanks for your comments and wishes!