Blocking a specific immune system enzyme protects brain cells and improves movement in Parkinson's models

A scientific breakthrough has revealed a potential new way to stop the loss of brain cells in Parkinson's. Published in July 2026, a collaborative study has demonstrated that blocking an immune system enzyme called 15-PGDH can powerfully shield vital brain cells from destruction, restore cellular balance, and significantly improve movement. The discovery is the result of a collaborative effort led by Dr Andrew A. Pieper and Dr Sanford Markowitz. The research was carried out by a team of scientists from several prominent institutions in Cleveland, Ohio, including University Hospitals Cleveland Medical Center, Case Western Reserve University, and the Cleveland VA Medical Center, alongside Dr Min-Kyoo Shin from Seoul National University. The research focused on the substantia nigra, which is the specific region of the brain where dopamine-producing cells are lost. By examining autopsied brain tissue from people who had Parkinson's, the team discovered that levels of the 15-PGDH enzyme were abnormally high. In a healthy brain, this enzyme breaks down a protective signaling molecule called prostaglandin E2. However, when 15-PGDH becomes overly active, it destroys too much of this protective molecule. This tips the brain cells into a state of severe oxidative stress and inflammation, creating a destructive cycle that ultimately kills the cells. To test if blocking this enzyme could save brain cells, the team used both genetic and chemical methods across three distinct mouse models that mimic different features of Parkinson's. In two of the models, mice were exposed to specific toxins and inflammatory triggers that normally cause rapid brain cell death and severe movement difficulties. The third model was driven by the accumulation of alpha-synuclein, the protein that clumps together in the brains of people with Parkinson's. The researchers tested a specific small-molecule inhibitor compound called SW033291, which was originally developed in Dr Markowitz's laboratory. Given orally, the drug successfully crossed the blood-brain barrier, penetrated deep into the brain, and achieved near-total suppression of the overactive enzyme for up to six hours at a time. The results were highly encouraging. In all three models, blocking the enzyme restored a healthy chemical balance. The treatment successfully lowered a trio of harmful elements consisting of a cell-death protein called lipocalin-2, an inflammatory molecule called interleukin-1-beta, and a specific free-radical generator called Nox2. By turning down this destructive trio, the treatment completely shielded the mice from the neuroinflammation, cell death, and motor impairment normally seen in these models. One of the most significant findings was that this protective effect occurred without changing the amount of alpha-synuclein clumps in the brain. Instead of trying to clear out the misfolded proteins, the treatment worked by directly disarming the brain's toxic damage-response and inflammatory machinery. This suggests that protecting the cells from the surrounding inflammation can keep them alive and functioning normally, even while the primary Parkinson's proteins remain present. Because this same enzyme is also being targeted by biotechnology companies to treat age-related muscle loss outside the brain, a next-generation 15-PGDH blocking drug named MF-300 has already successfully completed Phase 1 human clinical trials. Having this existing human safety data means that researchers do not need to design a new molecule from scratch. The Cleveland team is now preparing to map out the exact upstream signals that cause the enzyme to overflow in the first place, with the ultimate goal of rapidly repurposing these existing clinical-stage drugs for future Parkinson's clinical trials.