Scientists at Stanford Medicine have found a potential way to rescue brain cells that are dying in a certain type of Parkinson’s disease.
Their study, done in mice, shows that turning off an overactive enzyme might help restore lost communication in the brain and even begin to reverse early signs of the disease.
The findings were published in the journal Science Signaling.
In Parkinson’s disease caused by a specific genetic mutation, an enzyme called LRRK2 becomes too active. This damages the way brain cells talk to each other, especially in the dopamine system, which controls movement, motivation, and decision-making.
Dopamine is a chemical that helps brain cells send signals. When this system breaks down, movement problems like tremors and stiffness occur.
Dr. Suzanne Pfeffer, a senior author of the study, explained that blocking this enzyme early enough might slow or even stop the progression of Parkinson’s symptoms.
The team used a compound called MLi-2, which sticks to the enzyme and blocks its activity. This treatment might also help people with other forms of Parkinson’s disease, not just those with the known genetic mutation.
In a healthy brain, dopamine-producing neurons send messages to another brain region called the striatum. These messages rely on tiny structures on cells called primary cilia—like antennas that send and receive signals. But when the LRRK2 enzyme is overactive, many brain cells lose their cilia. This cuts off the signals and leads to cell damage.
One key message comes from a protein called “sonic hedgehog,” which helps other brain cells make protective proteins. These protect nearby neurons from dying. Without cilia, cells can’t receive this message, and fewer protective proteins are made, putting more cells at risk.
At first, the researchers tried feeding mice with the mutation the inhibitor for two weeks. There was no improvement. But inspired by a separate study on how brain cells involved in sleep grow and shrink their cilia regularly, they tried again—this time for three months. The result was impressive.
After three months of treatment, the cells in the striatum of mice with the Parkinson’s mutation looked like those of healthy mice. The primary cilia had grown back. This allowed signals from dopamine neurons to reach their target, and the protective response was restored. The researchers also saw signs that damaged neurons were starting to recover.
This finding suggests it might be possible not only to slow the disease but actually improve brain function. Pfeffer explained that early warning signs of Parkinson’s can appear up to 15 years before tremors begin.
These include loss of smell, constipation, and sleep disorders. The hope is that people with the LRRK2 mutation could start treatment early to prevent or delay symptoms.
The research team now plans to test whether this approach can help people with other forms of Parkinson’s that don’t involve the LRRK2 mutation. Several clinical trials for LRRK2 inhibitors are already underway.
The study was supported by The Michael J. Fox Foundation, the Aligning Science Across Parkinson’s initiative, and the UK Medical Research Council.
If you care about Parkinson’s disease, please read studies about Parkinson’s gene variant is found predominantly in people of African ancestry and research shows a dangerous cause of Parkinson’s disease.
For more about Parkinson’s disease, please read studies that exercise hormone may help stop Parkinson’s symptoms and scientists make new breakthrough in Parkinson’s disease treatment.
The study is published in Science Signaling.
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