Parkinson’s disease is one of the most common brain disorders in the world. It affects movement, balance, and coordination, and it gradually becomes worse over time.
More than one million people in the United States live with Parkinson’s disease, and thousands of new cases are diagnosed every year. Although doctors have treatments that can help reduce symptoms, there is still no approved therapy that can slow or stop the disease itself.
Now, researchers at the Perelman School of Medicine at the University of Pennsylvania have discovered an important clue that could change that situation.
Their study, published in the journal Neuron, identified a brain immune protein that appears to help Parkinson’s disease spread through the brain. The researchers believe that blocking this protein may one day help slow the disease in its earliest stages.
The protein is called glycoprotein nonmetastatic melanoma B, or GPNMB. While the name is complicated, its possible role in Parkinson’s disease is easier to understand. Scientists found evidence that this protein may help harmful damage move from one brain cell to another, allowing the disease to gradually affect more areas of the brain.
To understand why this matters, it helps to know how Parkinson’s disease develops. A protein called alpha-synuclein is thought to play a central role. In healthy brains, alpha-synuclein helps nerve cells function normally. But in Parkinson’s disease, the protein begins to fold incorrectly and form abnormal clumps inside brain cells.
These clumps damage the affected cells. Even worse, the abnormal protein can spread to nearby healthy cells, where it encourages more alpha-synuclein to clump together. This process is believed to help the disease move through the brain over time. As more brain regions become affected, symptoms become more severe.
Patients may first notice tremors, stiffness, or slower movement. As the disease progresses, they can develop problems with walking, balance, swallowing, and other daily activities.
The new study focused on microglia, which are immune cells that live in the brain. These cells normally help protect the brain by removing waste and responding to injury. However, the researchers found that when neurons become damaged in Parkinson’s disease, nearby microglia produce larger amounts of GPNMB.
Part of this protein is then released into the surrounding brain tissue, where it can move between cells. The researchers suspected that this process might help the harmful alpha-synuclein pathology spread.
To test their idea, they developed special antibodies designed to block GPNMB. Antibodies are proteins that can attach to specific targets in the body. In laboratory experiments using cultured brain cells, the antibodies successfully reduced the spread of alpha-synuclein damage from one cell to another.
The findings suggest that Parkinson’s disease may involve a vicious cycle. Alpha-synuclein damages neurons, which causes microglia to release more GPNMB. The extra GPNMB then helps alpha-synuclein spread further, creating even more damage.
The researchers believe that breaking this cycle could slow disease progression.
The team also wanted to know whether their findings were relevant to humans. To investigate, they analyzed tissue samples from 1,675 brains stored in the Penn Brain Bank. They found that people with genetic variations linked to higher GPNMB production tended to have more extensive alpha-synuclein pathology.
This provided additional evidence that GPNMB may play an important role in Parkinson’s disease progression. Interestingly, higher GPNMB levels were not associated with markers of Alzheimer’s disease or certain other neurodegenerative disorders, suggesting that the protein may be especially important in Parkinson’s disease.
Although the findings are exciting, researchers emphasize that the work is still in its early stages. The antibodies have not yet been tested as a treatment in human patients. Many additional studies will be needed to confirm safety and effectiveness before clinical trials can begin.
Source: University of Pennsylvania.
