Va and cwru researchers discover mechanism to protect mouse brain function following traumatic brain injury or alzheimer’s disease | va northeast ohio health care | veterans affairs

Research published this week in the official journal of the U.S. National Academy of Sciences portends a future, not too far in the distance, when brain degeneration following trauma might

be greatly reduced or eliminated. Findings indicate that a future drug administered to  battlefield servicemembers, car accident victims, and those seeing early signs of Alzheimer’s disease

(AD) could slow or even entirely halt the physiological cycle of brain function decline. Past research indicates the damage from traumatic brain injuries (TBI) continues to build and

increase following an initial event, with a steady increase in brain atrophy over time. This is of particular interest to VA doctors who observe that more than 65 percent of Veterans have

experienced at least one TBI, and in fact more than 20 percent of American adults have experienced at least one TBI in their lifetime. More than 55 million people are diagnosed with

Alzheimer’s disease annually—a condition that is closely linked to prior TBI. Indeed, TBI is the 3rd greatest risk factor, behind genetics and aging, for developing AD. It's no wonder

finding a treatment or intervention that could interrupt the associated steady mental decline of TBI and AD has been a high priority for researchers for decades. This new research, funded in

large part by the Valour Foundation with support from the VA and NIH, resulted from a six-year collaborative, multi-institutional, international study lead by VA researcher Dr. Andrew

Pieper(1) and CWRU researcher Dr. Sanford Markowitz(2), and involved another 47 global researchers. The key finding was that inhibiting the accumulation of a specific enzyme, known as

15-PGDH, protects the blood brain barrier and blocks the downward spiral of inflammation and brain cell damage, resulting in protection from cognitive decline—in mice.  The findings identify

inhibiting the enzyme 15-PGDH as an entirely new pathway to treatment related to brain degeneration, one that is not concerned with amyloid plaque development, which has been the primary

focus of researchers for over a decade. “The outcomes we observed in our study indicate real promise for the development of an entirely new preventative drug treatment for protecting

cognitive function after traumatic brain injuries (TBI)—such as those military servicemembers might experience in battle—as well as from Alzheimer’s disease; two of the most significant

problems in medicine today,” said Pieper. “Particularly exciting, was that the treatment worked even when administered 24 hours after the TBI incident,” said Pieper. “The chemical we

developed and used to inhibit 15-PGDH, dubbed SW033291, acts in an incredibly potent way,” Markowitz said. “It can inactivate this enzyme when present in blood or tissue at one part in 10

billion, which means it has real promise to work as a drug.” A related joint news release was published this morning by Case Western Reserve University on behalf of University Hospitals and

VA.  PRIMARY RESEARCHERS’ TITLED AFFILIATIONS:  1) Andrew A. Pieper, MD PhD; Psychiatrist, Geriatric Research Education and Clinical Center, Louis Stokes VA Medical Center; Rebecca E.

Barchas MD DLFAPA University Professor of Translational Psychiatry, Case Western Reserve University; Morley-Mather Chair in Neuropsychiatry, University Hospitals of Cleveland; Director,

Brain Health Medicines Center, Harrington Discovery Institute, University Hospitals Cleveland. 2) Sanford Markowitz, MD, PhD; Ingalls Professor of Cancer Genetics, Distinguished University

Professor, Case Comprehensive Center; Division of Hematology-Oncology, Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland.