4 ms·
It's always great to see new approaches to pharmaceutical development. It's a field that's desperately in need of a better approach. I do have to wonder, howev
by cge 11y ago
It's always great to see new approaches to pharmaceutical development. It's a field that's desperately in need of a better approach.
I do have to wonder, however, when having a focus on neurodegenerative diseases that are largely seen as proteopathies, how useful a method that is presumably targeting only gene expression can be, which is what I assume you're targeting. If the view of diseases like PD as prion-like diseases with perhaps randomly misfolded proteins that recruit others and propagate through the brain is correct, for example, will targeting gene expression be able to do that much beyond treating symptoms? And if targeting genes that are not necessarily
I'm divided on the usual search-of-preapproved-drug approach too. On the one hand, it vastly lowers costs, speeds up trials, and can actually make development somewhat feasible for startups, but on the other, it does really feel like searching through a bunch of drug candidates that have no reason why they'd be effective for your targets. It's unfortunate we don't have a better approach here. And of course, as I'm sure you know, success in mouse models often translates to nothing at all in humans.
I'd be curious to know what sort of genomic data you're actually using for your analysis.
Again, though, it's great to see a startup working in this area, and I'll look forward to seeing what you come up with.
- chenja 11y agoI 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!