Public release date: 24-Oct-2012 [ | E-mail | Share ]

Contact: Marla Paul marla-paul@northwestern.edu 312-503-8928 Northwestern University

CHICAGO --- In an early-stage breakthrough, a team of Northwestern University scientists has developed a new family of compounds that could slow the progression of Parkinsons disease.

Parkinsons, the second most common neurodegenerative disease, is caused by the death of dopamine neurons, resulting in tremors, rigidity and difficulty moving. Current treatments target the symptoms but do not slow the progression of the disease.

The new compounds were developed by Richard B. Silverman, the John Evans Professor of Chemistry at the Weinberg College of Arts and Sciences and inventor of the molecule that became the well-known drug Lyrica, and D. James Surmeier, chair of physiology at Northwestern University Feinberg School of Medicine. Their research was published Oct. 23 in the journal Nature Communications.

The compounds work by slamming the door on an unwelcome and destructive guest -- calcium. The compounds target and shut a relatively rare membrane protein that allows calcium to flood into dopamine neurons. Surmeiers previously published research showed that calcium entry through this protein stresses dopamine neurons, potentially leading to premature aging and death. He also identified the precise protein involved -- the Cav1.3 channel.

These are the first compounds to selectively target this channel, Surmeier said. By shutting down the channel, we should be able to slow the progression of the disease or significantly reduce the risk that anyone would get Parkinsons disease if they take this drug early enough.

Weve developed a molecule that could be an entirely new mechanism for arresting Parkinsons disease, rather than just treating the symptoms, Silverman said.

The compounds work in a similar way to the drugisradipine, which is commercially available FDAapproved for treatment ofhypertension, for which a Phase 2 national clinical trial withParkinson'spatients -- led by Northwestern Medicine neurologist Tanya Simuni,M.D. -- was recentlycompleted. Isradipine studies in Parkinson's disease aremoving forward, but because isradipinewas developed for treatment ofhypertension, it interacts with other channels found in the walls ofbloodvessels. This limits the dose of the drug that can be administered to patientswithParkinson's disease.

The challenge for Silverman was to design new compounds that specifically target this rare Cav1.3 channel, not those that are abundant in blood vessels. He and colleagues first used high-throughput screening to test 60,000 existing compounds, but none did the trick.

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Parkinson's breakthough could slow disease progression