A team of scientists at Northwestern University have discovered what might slow the progression of Parkinson's disease. This compound was developed by Richard B. Silverman at the Weinberg College of Arts and Sciences and creator of the molecule that became the drug Lyrica. This compound or rather the family of compounds work by blocking calcium flow in the brains neurons. The main mechanism is the suppression of a membrane protein, which allows calcium to flow into the dopamine neurons. With this membrane protein blocking calcium flow into the dopaime neuron it avoids further cell damage.
A team of scientists at Northwestern University have discovered what might slow the progression of Parkinson's disease. This compound was developed by Richard B. Silverman at the Weinberg College of Arts and Sciences and creator of the molecule that became the drug Lyrica.
This compound or rather the family of compounds work by blocking calcium flow in the brains neurons. The main mechanism is the suppression of a membrane protein, which allows calcium to flow into the dopamine neurons. With this membrane protein blocking calcium flow into the dopaime neuron it avoids further cell damage.
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D. James Surmeier, the chair of physiology at Northwestern previously published research which showed that calcium entry through the protein channel Cav1.3 stresses the dopamine neurons which could potentially lead to premature aging and death. The research team at Northwestern has previously published research showing how calcium entry through the protein channel Cav1.3 stresses the dopamine neurons, which has been shown to lead to premature aging and death.
"We've developed a molecule that could be an entirely new mechanism for arresting Parkinson's disease, rather than just treating the symptoms," Silverman explained.
A Phase 2 national clinical trail with Parkinson's patients was led by Northwestern Medicine neurologist Tanya Simuni, M.D. The new compound works in a similar way as the drug Isradipine (A calcium channel blocker used to reduce risk of stroke and heart attack). However Irasdiphine interacts with other channels found in the walls of blood vessels and Isradipine can not be used in a high enough concentration to be effective against Parkinson's.
One challenge for Silverman was in creating a new compound that would specifically target the rare Cav1.3 channel. He and his colleagues did a high-throughput screening to test 60,000 existing compounds, none of which did what Silverman required. Subsequently, Silverman looked at compounds he had developed for other neurodegenerative diseases and identified one compound he believed had promise. Soosung Kang, a postdoctoral associate in Silverman's lab was tasked with refining the molecules until they where able to only shut the Cav1.3. It took Mr. Kang 9 months to finally succeed.
"The drug relived the stress on the cells," Surmeier said. "We have a long way to go before we are ready to give this drug, or a reasonable facsimile, to humans, but we are very encouraged,"
The next step for the Northwestern team is to improve the pharmacology of the compounds to make them suitable for human use and eventually move to Phase 1 clinical trials.
The research was supported by Micheal J. Fox Foundation and the RJG Foundation.
Brain neurons image via Shutterstock
