An enzyme better known for its role in the immune system, 15-PGDH (15-hydroxyprostaglandin dehydrogenase), has emerged as a potential target for protecting brain cells from degeneration. Investigators at University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center found that inhibiting 15-PGDH was potently neuroprotective, working by restraining the production of reactive oxygen species that damage the brain. The work, published in the Proceedings of the National Academy of Sciences, was co-led by Andrew A. Pieper, MD, PhD, and Sanford Markowitz, MD, PhD, and received the 2025 Cozzarelli Prize in Biomedical Sciences.
The gap this addresses is a familiar one across neurodegenerative disease. Parkinson's is the second most common neurodegenerative condition, affecting more than ten million people worldwide, and the drugs available today manage symptoms without slowing the loss of neurons that drives the illness downward over time. A compound that interferes with the damage process itself, rather than compensating for its effects, would represent a different category of treatment.
The same team had previously identified 15-PGDH inhibition as a promising approach in other conditions, including Alzheimer's disease and traumatic brain injury. That overlap matters: oxidative damage is a shared feature of several neurodegenerative processes, so a drug that curbs it could in principle be relevant beyond any single diagnosis.
Pieper directs the Brain Health Medicines Center at the Harrington Discovery Institute at University Hospitals and is a psychiatrist and investigator at the Louis Stokes VA Geriatric Research Education and Clinical Center; Markowitz is a cancer geneticist at the Case Comprehensive Cancer Center and UH Seidman Cancer Center. The pairing reflects how the enzyme was first studied in other areas of medicine before its relevance to the brain became clear. Translating a laboratory target into a therapy people can take remains the long part of the road.