Parkinson’s disease is the second most common brain disease that causes the gradual loss of nerve cells, affecting more than 10 million people worldwide.
It mainly damages brain cells that produce dopamine, a chemical that helps control movement. As these cells die, people develop shaking, stiffness, slow movement, poor balance, and difficulty walking.
Many patients also experience depression, sleep problems, memory loss, and other non-movement symptoms. Although today’s medicines can improve symptoms, none can stop the brain cells from slowly dying.
Now scientists from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center have discovered a promising new treatment strategy that could one day help slow the disease itself. Their findings were published in the journal Redox Biology.
The research builds on earlier work in Alzheimer’s disease and traumatic brain injury. The scientists previously discovered that blocking an enzyme called 15-hydroxyprostaglandin dehydrogenase, or 15-PGDH, protected brain cells from damage.
This enzyme appears to increase harmful molecules known as reactive oxygen species, which can damage cells through a process called oxidative stress. Oxidative stress and inflammation are both believed to play major roles in Parkinson’s disease.
In the new study, the researchers examined brain tissue from people with Parkinson’s disease and found unusually high levels of 15-PGDH. They also studied three different mouse models of Parkinson’s disease. All three showed the same increase in the enzyme.
The team then blocked the enzyme using both genetic methods and an experimental drug. In both cases, the results were encouraging.
The treatment reduced inflammation in the brain, protected dopamine-producing nerve cells from dying, and improved movement in the mice. The scientists also discovered that blocking 15-PGDH reduced several harmful inflammatory substances that are known to damage brain cells.
Another exciting finding involved an experimental drug called SW033291, which was originally developed in the Markowitz Laboratory. Earlier research showed that the drug can enter the brain successfully and remain there for several hours while almost completely blocking the activity of the enzyme.
The researchers also point out that another 15-PGDH inhibitor called MF-300 has already completed a Phase I clinical trial for another medical condition without major safety concerns. This raises the possibility that drugs already being developed could be repurposed for Parkinson’s disease much faster than creating an entirely new medicine.
One surprising discovery was that the treatment protected brain cells without reducing the buildup of abnormal alpha-synuclein protein, which is widely believed to drive Parkinson’s disease. This suggests that reducing inflammation and protecting brain cells may be enough to slow disease progression even if abnormal proteins remain present.
The research team plans to continue studying exactly how the enzyme contributes to brain damage and why its levels increase during Parkinson’s disease. Understanding these processes could lead to even more effective treatments in the future.
This research provides strong evidence from laboratory studies and multiple mouse models that blocking the 15-PGDH enzyme may protect brain cells in Parkinson’s disease. It is especially encouraging because a similar inhibitor has already completed an early Phase I safety trial for another condition, which could speed future development.
However, these findings have not yet been proven in people with Parkinson’s disease. Human clinical trials will be needed to confirm whether this approach is safe and can truly slow disease progression.
Even so, the study opens an exciting new direction by focusing on reducing brain inflammation and damage rather than directly targeting the abnormal proteins linked to Parkinson’s disease.
If you care about Parkinson’s disease, please read studies that Vitamin B may slow down cognitive decline, and Mediterranean diet could help lower risk of Parkinson’s.
For more health information, please see recent studies about how wheat gluten might be influencing our brain health, and Olive oil: a daily dose for better brain health..
Source: University Hospitals / Case Western Reserve University.
