Dr. Anatol Kreitzer has spent years shedding new light on the neural pathways of Parkinson's disease. In fact, when ABC7 first met him, he was using lasers to coax the neurons into firing, allowing him to map them. "The first step was to identify which circuits are actually affected in Parkinson's disease, and that's what we did," he said.
That laser mapping allowed him to move to the next logical step, looking for a way to interrupt the malfunctioning circuits that cause the symptoms of Parkinson's. After crunching data on hundreds of candidates, his team at San Francisco's Gladstone Institutes zeroed in on a tiny protein called RGS4. It regulates signaling in the part of the brain responsible for movement. "RGS4 becomes overactive in Parkinson's disease and it actually causes these circuits to become overactive as well," Kreitzer explained.
But the team was also looking for a cause and effect. Scientists have long known that a drop in dopamine is associated with the onset of Parkinson's. So, Kreitzer's team wanted to test the relationship between dopamine and RGS4.
The team used two sets of mice, one with normal levels of RGS4, the other with RGS4 removed. When they lowered the levels of dopamine, the set with RGS4 in their cells began to stop grooming and began to move erratically. The other group was unaffected, suggesting that RGS4 acts as a kind of messenger, after the loss of dopamine. "Almost all of the therapies in Parkinson's target the dopamine receptor itself," Kreitzer explained. "And, this is actually going downstream in the dopamine receptor, into signaling pathways that dopamine can control."
He says that is significant because current drugs for Parkinson's tend to become less effective as the diseases progresses, but targeting the signaling pathways could offer a fresh approach for drug treatments. "Even with people who've lost a significant number of dopamine neurons, and we're talking 10 million people around the world who already suffer from the disease, this is a symptomatic treatment that has the potential to normalize motor behavior," Kreitzer said.
And it could someday, perhaps, interrupt the debilitating symptoms of Parkinson's disease. Kreitzer says it could take several years to test compounds that target RGS4, but he believes human trials could be possible within the decade.