For decades, scientists have searched for treatments that can do more than simply relieve the symptoms of Parkinson’s disease.
While current medications can help people move more easily and improve quality of life, they do not stop the disease from continuing to damage the brain. A new study from researchers at the University of Pennsylvania offers hope that this may someday change.
The research, published in the journal Neuron, points to a little-known immune protein called GPNMB as a possible driver of Parkinson’s disease progression. The findings suggest that blocking this protein with specially designed antibodies could eventually help slow the disease before severe symptoms develop.
Parkinson’s disease is a progressive neurological condition that affects movement and coordination. It develops when brain cells that help control movement gradually become damaged and die.
Symptoms often begin slowly and may include tremors, stiffness, slower movements, and balance problems. Over time, these difficulties can become more severe and interfere with everyday life.
One of the biggest mysteries in Parkinson’s disease is how the damage spreads through the brain. Scientists know that a protein called alpha-synuclein is heavily involved. In people with Parkinson’s disease, alpha-synuclein forms abnormal clumps inside nerve cells. These clumps are toxic and can damage the cells where they form.
Researchers have also discovered that these harmful protein clumps can spread from one neuron to another. This process allows the disease to gradually affect larger areas of the brain. However, scientists have not fully understood what helps this spread occur.
The University of Pennsylvania team focused on GPNMB, a protein produced by microglia. Microglia are the brain’s immune cells and play an important role in maintaining brain health. They respond to injury, remove damaged material, and help protect neurons.
The researchers found that when neurons become injured by alpha-synuclein, microglia increase their production of GPNMB. Some of the protein is then released into the surrounding brain environment.
This observation led the scientists to suspect that GPNMB might help the disease spread.
To investigate further, they created monoclonal antibodies designed to block GPNMB activity. Monoclonal antibodies are laboratory-made proteins that can attach to specific molecules and prevent them from carrying out their normal functions.
In experiments using cultured neurons, the antibodies successfully reduced the spread of alpha-synuclein-related damage between cells. This suggested that GPNMB may act as a key link in the chain of events that allows Parkinson’s disease to progress.
The researchers describe a self-reinforcing process. First, alpha-synuclein accumulates and damages neurons. The damage triggers microglia to release more GPNMB. The additional GPNMB then promotes further spread of alpha-synuclein, leading to even greater neuronal injury.
By interrupting this cycle, scientists hope they may be able to slow the disease.
The team also looked for evidence in human brains. They examined 1,675 brain samples from the Penn Brain Bank and analyzed genetic information related to GPNMB production. People with genetic traits linked to higher GPNMB levels tended to have greater alpha-synuclein pathology.
This finding supported the laboratory results and suggested that the protein plays an important role in real human disease, not just experimental models.
Another encouraging observation was that GPNMB did not appear strongly linked to markers of Alzheimer’s disease. This raises the possibility that therapies targeting GPNMB could be particularly useful for Parkinson’s disease.
Despite the promising results, the researchers caution that much work remains. The antibodies have not yet been tested in human clinical trials, and scientists still need to determine whether blocking GPNMB is safe over the long term.
Because GPNMB is part of the immune system, researchers must carefully evaluate whether interfering with it could have unintended effects.
Source: University of Pennsylvania.
