By Kukla Vera
USC Professors Roberta Diaz Brinton, PhD, of the USC School of Pharmacy and Lon Schneider, MD, MS, of the Keck School of Medicine of USC are principal investigators of a newly funded study from the National Institutes of Health, aimed at testing promising drugs for the prevention of Alzheimer’s disease.
The USC project, “Allopregnanolone Regenerative Therapeutic for MCI/Alzheimer’s: Dose Finding Phase 1,” is the first clinical trial to evaluate the safety and tolerability of using allopregnanolone (Allo), a natural brain steroid, in treating mild cognitive impairment and Alzheimer’s disease, as part of an intensified national effort to find effective interventions for the degenerative brain disease.
With $2.4 million in new funding from the NIH, the study builds on Brinton’s research that has shown that Allo promotes the generation of new brain cells, reduces amyloid levels and restores cognitive function in pre-clinical animal testing. The clinical trial will evaluate the safety and tolerability of the drug over 12 weeks.
“The NIA grant provides an extraordinary opportunity to advance our discovery and translational research on Allo to a clinical trial,” said Brinton, who holds the R. Pete Vanderveen Chair in Therapeutic Discovery and Development at the USC School of Pharmacy. “Our research has shown that Allo activates neural stem cells in the brain to generate new nerve cells and to restore cognitive function while also reducing the pathology of Alzheimer’s. Allo is the first regenerative therapeutic for Alzheimer’s that has the potential to regenerate nerve cells and the pathways necessary for memory.”
The study is among the first to be developed with direction from the 2012 NIH “Alzheimer’s Disease Research Summit: Path to Treatment and Prevention,” and reflects research goals in the “National Plan to Address Alzheimer’s Disease,” according to the announcement from the National Institute of Aging, the lead agency within the NIH for Alzheimer’s research.
NIA has supported Brinton’s research over many years, including basic science grants to understand allopregnanolone’s mechanism of action in the brain, a drug development grant which included development of optimal dose and formulation, and support for pre-clinical toxicology studies. This new support helps bring Brinton and Schneider’s research to a human phase 1 trial.
The additional funding supports translational research focused on identifying, characterizing and validating new therapies to stop the progression of the disease.
“Our allopregnanolone project is a paradigm shift in treating Alzheimer’s disease — away from the current, experimental, anti-amyloid strategy and toward a novel, nerve cell regenerative therapeutic strategy that has not been tested previously in humans,” said Schneider, who directs the USC California Alzheimer Disease Center and the clinical core of USC’s NIH-funded Alzheimer Disease Research Center. “This early phase trial will allow us to determine dosage levels in patients with early Alzheimer’s disease and to evaluate the potential for therapeutic effect by using brain imaging and cognitive function testing.”