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Monday, May 11, 2015

Prions, the Pipeline, and the Latest in Parkinson Disease



Bret S. Stetka, MD, Maurizio Facheris, MD, MSc
 Disclosures
May 08, 2015
Dr Facheris: Another question is what are we measuring when we look at synuclein, because it comes in so many different forms: soluble oligomers, dimers, fibrils, and clumps. The detection methods used now are primarily for total synuclein. So it's hard to determine which type the antibodies are attacking.
Medscape: And here, can't you run into the same problem we do with AD: asking whether or not the synuclein—and the amyloid, in the case of AD—is the pathologic culprit itself, or instead a by-product of some other pathologic mechanism? I know the prion theory suggests that it might be the primary cause, correct?
Dr Facheris: My take on this is that the community is moving toward thinking that synuclein is actually driving PD pathology. And yes, the thought is it involves this whole prion-like theory, the idea that PD and other neurodegenrative diseases are caused by misfolded proteins that propagate from neuron to neuron. Again, we don't know which form of synuclein might be causing disease. But we think that either there is cell-to-cell communication, or synuclein leaves the cell and somehow gets into another.
An imaging agent that binds to alpha-synuclein in vivo, and more specifically that binds to clumps, would not only help us confirm the diagnosis of PD, but also assess the pathologic load that a person with PD has and its distribution. It would also help us assess whether therapies that target those clumps are able to prevent new clumps from building up or dissolve the ones already formed in the brain, and ultimately show the slowdown or stopping of the progression of the disease.
One other thing gaining momentum is LRRK2 biology. We're close to determining the structure and function, and companies are working to develop LRRK2 kinase inhibitors that I think could be promising.
Medscape: Any final thoughts?
Dr Facheris: There is so much promising work going on in PD, which is very exciting. At the Foundation, we work with academia, biotech, and pharma, and we like to bring together companies and get the ball rolling. But we also like the moment when they go back to competing. That means we truly paved the road, and they take over and compete to drive more innovation.
http://www.medscape.com/viewarticle/844223_2?src=stfb

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