As with most neurodegenerative diseases, progressive supranuclear palsy (PSP) can be traced to proteins that “misbehave”—folding on themselves in an inappropriate way. Those misfolded proteins then stick together and form stacks called fibrils, which in turn form larger accumulations. “In the case of PSP, the protein that is misfolded is called tau, while in [Parkinson's disease], the protein is alpha-synuclein,” says Lawrence Golbe, MD, emeritus professor of neurology at Rutgers Robert Wood Johnson Medical School in New Brunswick, NJ; chief clinical officer and scientific advisory board chair of CurePSP; and author of A Clinician's Guide to Progressive Supranuclear Palsy (Rutgers University Press, 2018).

Unfortunately, two clinical trials of treatments for PSP targeting the tau protein failed in 2019. “Not everybody has given up on anti-tau monoclonal antibody therapies, but there are multiple other mechanisms that are currently being explored,” says Alex Pantelyat, MD, professor of neurology and director of the Atypical Parkinsonism Center at Johns Hopkins University in Baltimore. “I would argue that the pipeline is the best that it's ever been.”

In fact, clinical trials of three drugs to slow PSP progression are underway; FNP-223 prevents tau protein from misfolding, AMX-0035 addresses both the mitochondrial- and protein-regulation issues of PSP, and NIO-752 reduces tau production by jamming its messenger RNA. A fourth drug, the immune modulator GV-1000, is set to begin its US trial this year.

The nonprofit organization CurePSP, meanwhile, has partnered with the University of California, San Francisco, on a new “platform” clinical trial that will test three drugs (and potentially more) concurrently, with a single placebo arm, at up to 50 sites nationwide. Platform trials use specialized statistical tools to test multiple drugs at the same time, and new drug regimens can be added as they become available.

“This is a very exciting, novel clinical trial approach,” Dr. Pantelyat says. “The chances for a given participant to get an active study drug versus placebo are much better than with a trial testing only one drug, which should improve enrollment.” CurePSP expects enrollment to begin this fall.

Read More

Former Representative Jennifer Wexton Breaks Barriers with AI-Generated Voice Amid PSP Battle