The awards, made to investigators across the United States, are meant to fund an ambitious set of projects seeking to develop new drugs for disorders of the nervous system. Surmeier will be the first Blueprint researcher to focus on Parkinson’s disease (PD).
“The drug pipeline for disorders of the nervous system has really slowed to a trickle and there are a lot of major pharmaceutical companies that have pulled back from neuroscience because they think it’s too hard of a nut to crack,” said Surmeier, Nathan Smith Davis Professor of Physiology. “The NIH, and Director Francis Collins in particular, developed this idea that one way of increasing the flow of new compounds into the therapeutics pipeline is to fund the interaction between academics, whose real skill is in target discovery, and the pharmaceutical industry, which is very good at drug development.”
Caused by the progressive deterioration of neurons, PD affects the nerve cells that produce a vital brain chemical known as dopamine. Dopamine serves as a chemical messenger allowing communication between different parts of the brain, serving to coordinate smooth and balanced muscle movement. A lack of dopamine results in abnormal nerve functioning, causing a loss in the ability to control body movements.
When Surmeier identified a drug being used to treat high blood pressure as holding the potential to help fight Parkinson’s, his investigative curiosity took root. The drug, which prevented calcium entry into the dopamine-releasing neurons whose death causes PD, became a major focus of his research.
“The main target of that drug is a closely related but different calcium channel than the one we think is involved with Parkinson’s,” Surmeier explained. “That was the rationale for developing a more selective drug compound.”
Working with Richard Silverman, professor of chemistry, the pair used newly purchased equipment and the drug screening facility in Evanston to screen some 75,000 compounds, identifying a few and working to improve selectivity.
“We had a compound with properties that made it a good candidate for an orally-deliverable drug, and we brought this proposal to NIH,” Surmeier said. “The NIH has indicated that we are much further along than other Blueprint projects in the past because we have gone through some lead development, medicinal chemistry, a fair amount of toxicity testing, and even in vivo work.”
Through the Blueprint grant, the NIH is prepared to spend in excess of $1 million per year through funding of pharmaceutical company partners to push the drug forward. The NIH is also paying the Surmeier lab about $125,000 a year to do in vivo testing with compounds that are developed by the team.
Currently, there is no proven neuroprotective treatment for Parkinson’s disease, which is the second most common neurodegenerative disease in America, after Alzheimer’s. Because it is a disease primarily of aging, Surmeier expects the number of people suffering from PD to double in the next 15 years.
“One of the very interesting parts about the Blueprint is that the NIH funds the work, but allows the host academic institution from which the project originates to hold full intellectual property,” Surmeier said. “They are giving us the resources to do what we could do with private money, and giving us pretty much full control and not asking for anything in return other than we work hard to bring the drug to clinical trials.”