CLEVELAND – Whole brain radiotherapy (WBRT) saves lives by treating cancer that has spread to the brain, but it also causes long-standing brain damage. Many patients who go through radiation treatment later develop memory problems, thinking difficulties, and depression because the WBRT creates chronic oxidative stress in the brain. There are currently no medicines that adequately prevent this, so patients endure these effects of WBRT that significantly lower their quality of life.
Now, a research team from University Hospitals, Case Western Reserve University and the Louis Stokes Cleveland VA Medical Center has discovered that an experimental neuroprotective drug, P7C3-A20, could protect the brain from these harmful side effects of WBRT.
The study, led by the Pieper Laboratory , published today in Redox Biology.
“The results of our study were very encouraging,” said Andrew A. Pieper, MD, PhD, senior author of the study, University Hospitals Morley-Mather Chair of Neuropsychiatry, and Rebecca E. Barchas MD DLFAPA Case Western Reserve University Professor of Translational Psychiatry.
“In mice, WBRT caused chronic oxidative stress in the brain, most severely in the hippocampus, which is a region of the brain that is critical for learning, memory and mood,” explained Dr. Edwin Vázquez-Rosa, PhD, Assistant Professor of Psychiatry in the Pieper Lab and lead author of the study. “In the mice, this damage led to memory loss and depression-like behaviors. These debilitating effects continued for a year, which is the equivalent of decades in people. Daily treatment with P7C3-A20, a neuroprotective compound that stabilizes brain nicotinamide adenine dinucleotide (NAD + ) homeostasis, reduced that oxidative stress and prevented hippocampal damage, as well as cognitive impairment and depression-like activity in the mice.”
“The strength and breadth of protection were particularly exciting,” Dr. Pieper added. “P7C3-A20 suppressed neuroinflammation, protected both nerve cells and microglia, and prevented blood-brain barrier deterioration. Importantly, P7C3-A20 did not reduce the cancer-killing effects of radiation, and the mice tolerated P7C3-A20 treatment well over the entire year.”
Dr. Pieper is also the Director of the Brain Health Medicines Center at the Harrington Discovery Institute at UH, serves as Psychiatrist and Investigator in the Louis Stokes VA Geriatric Research Education and Clinical Center (GRECC), and is co-founder of Glengary Brain Health, Inc, a company formed to further develop and commercialize this technology.
Next steps in this research involve testing P7C3-A20 with different radiation schedules and doses and defining the shortest effective time window after WBRT.
“If these findings translate to humans, stabilizing brain energy balance (NAD + homeostasis) by adding a drug like P7C3-A20 to WBRT could preserve cognition and mood without reducing the ability of radiation treatment to control cancer,” emphasized Dr. Pieper.
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This study was conducted in collaboration with teams at Cleveland Clinic, Johns Hopkins and the University of Iowa Carver College of Medicine. Major fundings came from The Valour Foundation, the University Hospitals Morley-Mather Chair in Neuropsychiatry, the Case Western Reserve University Rebecca E. Barchas MD DLFAPA University Professorship in Translational Psychiatry. Two authors (Drs. Edwin Vázquez-Rosa and Andrew Pieper) hold patents on P7C3 compounds. Dr. Andrew Pieper is a co-founder of Glengary Brain Health.
Vázquez-Rosa, Edwin et al. “P7C3-A20 prevents whole brain radiotherapy-induced chronic hippocampal redox imbalance and neuropsychiatric impairment in mice.” Redox Biology . DOI: 10.1016/j.redox.2026.104052.
About University Hospitals / Cleveland, Ohio
Founded in 1866, University Hospitals serves the needs of patients through an integrated network of more than 20 hospitals (including 5 joint ventures), more than 50 health centers and outpatient facilities, and over 200 physician offices in 16 counties throughout northern Ohio. The system’s flagship quaternary care, academic medical center, University Hospitals Cleveland Medical Center, is affiliated with Case Western Reserve University School of Medicine, NEOMED, Oxford University, Technion Israel Institute of Technology, and National Taiwan University College of Medicine. The main campus also includes the UH Rainbow Babies & Children's Hospital, ranked among the top children’s hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, with more than 3,400 active clinical trials and research studies underway. UH Cleveland Medical Center is perennially among the highest performers in national and international ranking surveys, including “America’s Best Hospitals” from U.S. News & World Report and UK Brand Finance. UH is also home to 19 Clinical Care Delivery and Research Institutes. UH is one of the largest employers in Northeast Ohio with more than 30,000 employees. Follow UH on LinkedIn , Facebook and Twitter . For more information, visit UHhospitals.org .
About Case Western Reserve University
As one of the fastest-growing research universities in the United States, Case Western Reserve University is a force in career-defining education and life-changing research. Across our campus, more than 12,000 students from around the world converge to seek knowledge, find solutions and accelerate their impact. They learn from and collaborate with faculty members renowned for expertise in medicine, engineering, science, law, management, dental medicine, nursing, social work, and the arts. And with our location in Cleveland, Ohio—a hub of cultural, business and healthcare activity—our students gain unparalleled access to academic, research, clinical and entrepreneurial opportunities that prepare them to join our network of more than 125,000 alumni worldwide. Visit case.edu to see why Case Western Reserve University is built for those driven to be a force in the world.
About VA Northeast Ohio Healthcare System
Focusing on treating the whole Veteran through health promotion and illness prevention, VA Northeast Ohio Healthcare System provides comprehensive, seamless health care and social services for more than 140,000 Veterans across Northeast Ohio. With 17 locations of care, including 12 outpatient clinics, two community resource and referral centers, a psychosocial rehabilitation and recovery center, a chronic dialysis center, and an outpatient surgery center, VA Northeast Ohio Healthcare System’s quality services are easily accessible to Veterans in 21 counties. VA Northeast Ohio Healthcare System also contributes to the future of medicine through education, training, and research programs.
For more information about programs and services offered by VA Northeast Ohio Healthcare System, visit www.cleveland.va.gov or follow us on Facebook @ClevelandVAMC.
Redox Biology
Animals
. “P7C3-A20 prevents whole brain radiotherapy-induced chronic hippocampal redox imbalance and neuropsychiatric impairment in mice.”
11-Feb-2026