ARPA-H funding will launch accelerated drug-testing platform for Alzheimer’s disease at Mass General Brigham

McCance Center for Brain Health researchers will spearhead an innovative national effort using blood-based biomarkers to swiftly evaluate combinations of repurposed FDA-approved drugs and natural products aimed at preventing or slowing Alzheimer's disease progression

A new effort is underway to rapidly identify the most promising therapeutic candidates for preventing and slowing Alzheimer's disease progression. Researchers at Mass General Brigham have been awarded up to $41 million over four years from the Advanced Research Projects Agency for Health (ARPA-H) Open external link in a new window , an agency within the U.S. Department of Health and Human Services, to lead a multi-institutional Alzheimer's disease platform trial. In a platform trial, several potential treatments are tested at the same time using shared infrastructure. The team will test drugs already approved by the U.S. Food and Drug Administration for other conditions, as well as natural products (compounds derived from plants and other natural sources). They will use blood tests to look for early signs that a treatment is positively affecting Alzheimer's-related changes in the body.

The project, titled "Platform Trial for Biomarker-Guided Alzheimer's Disease Prevention," will be led by Principal Investigator Rudolph Tanzi, PhD, the Joseph P. and Rose F. Kennedy Professor of Neurology and Director of the McCance Center for Brain Health within the Mass General Brigham Neuroscience Institute, together with Gene Bowman, ND, MPH, McCance Center Clinical Trials Director and Assistant Professor of Neurology.

"Alzheimer's disease therapies are often evaluated too late in the disease progression, after substantial neurodegeneration has already occurred," said Tanzi. "This program aims to start interventions earlier, identify the most promising therapies rapidly, and, ultimately, uncover strategies to prevent progression before neurodegeneration begins."

The platform is modeled on the trial design used by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital to accelerate the search for treatments for amyotrophic lateral sclerosis (ALS), another devastating neurological condition. Rather than testing one treatment at a time, investigators plan to evaluate 5 to 10 regimens at once.

Blood-based biomarkers allow researchers to assess potential treatment effects more quickly and less invasively than traditional approaches. To find early signs that an investigational therapy may be affecting Alzheimer's-related changes in the body, researchers will evaluate changes in plasma p-tau217, a protein linked to Alzheimer's disease. They will also assess other biomarkers of Alzheimer's pathology, including Abeta42/Abeta40, GFAP, and NfL. Regimens that show promising signals could then advance to larger studies that measure effects on memory and daily function.

In parallel with the platform trial, the team will continue a standalone trial of its most promising natural product combination, known as NPC1. The research team will also use advanced analytics to help prioritize candidates emerging from laboratory screening studies.

Participants in the trials will be enrolled from across the United States. Participants will be cognitively unimpaired or mildly impaired with biomarker evidence of the early stages of Alzheimer's disease.

Tanzi and Bowman have brought together a broad consortium of investigators to carry out this work. Collaborators include the Neurological Clinical Research Institute (NCRI), as well as the Clinical Translational Research Unit (CTRU) within Massachusetts General Hospital and the Alzheimer's Disease Cooperative Study (ADCS) based at University of California-San Diego (UCSD). Key Mass General Brigham researchers include co-investigators Hiroko Dodge, PhD, and Sabrina Paganoni, MD, PhD.

"One-drug-at-a-time development is slow and costly. For neurological diseases such as Alzheimer's disease, we need solutions that move as rapidly as possible to find better therapies for our patients," said Bowman. "The platform trial approach has the potential to transform the pace of discovery and the way we care for our patients."

The Henry and Allison McCance Center for Brain Health, established in 2018, is directed by Tanzi and co-directed by psychiatrist, Gregory Fricchione, MD Open external link in a new window . The Center is dedicated to translational and clinical research with the mission of promoting healthy brain aging and prevention of neurodegenerative disease through innovative programs including lifestyle interventions based on the SHIELD protocol - Sleep, Handling Stress, Social Interaction, Exercise, Lifelong Learning and Diet. The McCance Center Alzheimer's Disease Prevention Platform Trial, directed by Bowman, conducts clinical testing of novel Alzheimer's disease therapies, including repurposing of FDA-approved drugs, natural products and lifestyle interventions emphasizing a brain-healthy diet.

This research was, in part, funded by the Advanced Research Projects Agency for Health (ARPA-H). The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the United States Government.