A new study led by Stanford Medicine researchers offers promising news for people with a type of Parkinson’s disease caused by a specific genetic mutation.
The mutation causes an enzyme called LRRK2 to become overactive, which interferes with brain cell communication and leads to the death of dopamine-producing neurons. These neurons are essential for movement, motivation, and decision-making.
Using a mouse model, the research team found that reducing the activity of LRRK2 using a compound called MLi-2 could protect brain cells and restore damaged communication networks. The findings were published in Science Signaling and suggest that early treatment might slow or even improve symptoms of Parkinson’s disease.
Dopamine neurons connect with a region of the brain called the striatum. Normally, they send signals to support cells called glia and other neurons. When LRRK2 is too active, it disrupts a key part of these cells—the primary cilia. These tiny, antenna-like structures help cells receive and send chemical messages.
Without them, cells can’t respond to important signals, including one called sonic hedgehog. This signal prompts the striatum to produce neuroprotective proteins, which help keep neurons alive. When cilia are lost, this signal fails, and brain cell death accelerates.
The study’s senior author, Dr. Suzanne Pfeffer, said this cilia loss may be one reason brain cells start to die. “Cilia are needed for cells to survive and receive messages that keep them alive,” she explained.
To test their theory, the team gave mice with the LRRK2 mutation the inhibitor drug MLi-2. They tried a short two-week treatment first but saw no changes. Inspired by other research showing that even non-dividing cells can grow and shrink cilia over time, the team extended the treatment to three months.
The results were striking. The percentage of brain cells with restored primary cilia was the same in treated mice as in healthy ones. This meant communication between dopamine neurons and the striatum was working again.
The striatum also resumed making neuroprotective proteins, and the dopamine neurons showed signs of recovery. Their stress levels dropped, and more dopamine nerve endings were detected in the brain.
Dr. Pfeffer said this offers hope that we might not only slow Parkinson’s progression but potentially reverse some of the damage if treatment begins early. “These findings suggest that it might be possible to improve, not just stabilize, the condition of patients with Parkinson’s disease,” she said.
Parkinson’s symptoms typically begin about 15 years before tremors appear. Early signs include loss of smell, constipation, and sleep problems. Dr. Pfeffer hopes that people known to carry the LRRK2 mutation might start treatment early enough to protect their brain cells before much damage occurs.
Although this study focused on genetic Parkinson’s, researchers believe the findings may apply more broadly. There are several clinical trials already underway using LRRK2 inhibitors, and this mouse research supports those efforts. The next step is to test whether the same benefits are seen in people who don’t have the LRRK2 mutation.
Dr. Pfeffer and her team are hopeful. “We are so excited about these findings. They suggest this approach has great promise to help patients by restoring activity in this brain circuit,” she said.
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.
The study is published in Science Signaling.
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