Road test for a Roadmap

This is a request for your suggestions to improve/amend CurePSP’s research plan, which is now two years old.

Here’s a link to the first and current version of our Research Roadmap:  Roadmap for Symposium 2013. You can also find it here.

It was designed as a guide to grant applicants and donors who want to know what CurePSP is interested in funding.  That’s not to say that we wouldn’t fund other things, but proposals that fit into the Roadmap’s model are viewed more favorably in our grant review process.

The elevator explanation of the model is that it uses unbiased gene searches to identify new risk genes, then finds drug targets among the proteins in the related gene products or cellular pathways, then tests those drugs in lab models, then turns to Pharma to develop those drugs clinically.  Along the way, it calls for new models and new clinical markers to assist in the process.

Clearly, The Roadmap ignores important things such as symptomatic treatments, toxic etiologies, clinical characterization, epidemiology and neurophysiologic analysis, not to mention serendipitous neuroprotective treatments with unclear mechanism.  But it provides a focus and an orientation.

So please use the Comments function to leave me your suggestions for improvement.  Keep in mind that the Roadmap should remain relatively simple and generic.  We don’t want to direct research from the top down.  On the other hand, we don’t want the document to be so generic as to be useless.

Obviously, feel free to respond to others’ comments; and have fun!


Just a residue full of sugar . . .

I’ve been jolted out of my non-posting torpor by CurePSP’s annual International Research Symposium, held on November 6 in La Jolla. The lecture hall was smack dab on the beach and despite the quality of the presentations, it was easy for the eye to wander from the lectern to the doorway framing a view of swaying palms and the blue Pacific. Thanks to Jeff Friedman for arranging the venue. Anyway, I’ll be describing some of the goings-on in this post and the next few.
Two of the presentations, both from pharma scientists, described drugs in development for PSP that reduce tau aggregation by inhibiting OGA (O-GlcNAcase; pronounced “oh-GLY-na-kaze”). That enzyme removes the sugar N-acetyl-beta-D-glucosamine from either serine or threonine residues of proteins. The opposing reaction, catalyzed by O-GlcNAc transferase, like other post-translational modifications, is a common way for cells to regulate proteins. In the case of tau, having that sugar in place reduces aggregation.
All of the OGA inhibitors being developed are small molecules suitable for oral administration. The smaller company with an OGA inhibitor program is Asceneuron, based in Lausanne, Switzerland. They expect to start a Phase I human trial in 2016 although they are still in an early stage of mouse model trials and they haven’t settled on one lead compound for further development. The larger company, Merck, is at a more advanced stage. Their drug, MK-8719, has shown that it can slow brain degeneration in mice transgenic for one of the FTD MAPT mutations. The drug also inhibits tau aggregation in a human iPSC line and in an early Phase I human trial in healthy volunteers was found to be well-tolerated and to increase O-GlcNAcylation in blood mononuclear cells.
Let’s hope that both companies move their OGA inhibitors to Phase II trials in the next couple of years.