Clinical Trials Begin for PU-AD--Potential Alzheimer’s Therapy With New Target

The Food and Drug Administraion (FDA) has cleared the new drug application for PU-AD (Samus Therapeutics, Topsfield, MA), allowing a phase 1 clinical trial to begin. An investigational agent, PU-AD is the first to target heat shock proteins (HSPs) and epichaperomes in Alzheimer's disease (AD). There has been increasing interest in exploring new treatment targets for AD as many clinical trials of drugs targeting the neurotoxic protein aggregates of amyloid or tau, known to accumulate in AD, have been unsuccessful. 

The phase 1 study will be a single ascending dose study to evaluate safety and tolerability of PU-AD in healthy individuals and is expected to be followed by a multiple ascending dose (MAD) cohort. If those trials are successful, a phase 1b/2 study is anticipated in the first half of 2020. 

Dr. Jeffrey Cummings, a principal clinical advisor to Samus, said, "Testing of an entirely new target deeply implicated in the progression and even initiation of pervasive neurodegenerative diseases is very exciting. I look forward to understanding full potential of new therapies in an area with enormous public health consequences." Dr. Cummings is founding director of the Cleveland Clinic Lou Ruvo Center for Brain Health, vice-chare for research, Department of Brain Health, University of Nevada, Las Vegas, and a member of Practical Neurology’s editorial board.

Epichaperomes are protein complexes that are “seeded,” or nucleated by HSP 90 in diseased cells that drive programmed cell death processes. These complexes have been found in multiple neurodegenerative diseases, including AD. It is hoped that by inhibiting HSP 90 and thus inhibiting epichaperomes the aggregation and hyperphosphorylation of tau, as well as other downstream pathophysiologic processes in AD, will be inhibited.