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Vanderbilt forges path for academia
NASHVILLE, Tenn.—Directing a combination of team science culture, infrastructure, business expertise and can-do spirit toward systematically delivering novel drug candidates to treat serious brain disorders, Vanderbilt University is not only providing an unmet need, but also forging a path for other academic institutions to follow.
"There is a crying need for better drugs to treat people with serious brain disorders, such as Parkinson's disease and schizophrenia—and for better ways to treat children with autism," says Jeffrey Conn, director of the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD).
Just last month, Vanderbilt announced new therapies for Parkinson's disease, schizophrenia and Fragile X syndrome, a direct result of its plan to bring new drugs to market. The new Vanderbilt compounds, developed with support from the Michael J. Fox Foundation for Parkinson's Research (MJFF), bypass the dopamine system altogether and instead modulate the activity of a specific glutamate receptor called mGlu4.
Research suggests that excessive signaling through another glutamate receptor, mGluR5, may contribute to manifestations of Fragile X syndrome, which include impaired cognitive function, developmental delay, attention deficit and hyperactivity, anxiety, obsessive-compulsive and autistic behaviors.
With support from the company, the Vanderbilt researchers have developed drug candidates that may improve Fragile X symptoms by "tuning down" the mGluR5 activity. Conn and his team have also identified chemical compounds that work in a fundamentally different way, by inhibiting glycine transporter one (GlyT1). This allows for more normal function of brain cells involved in schizophrenia.
In a transaction announced this month, Vanderbilt licensed the compounds to Karuna Pharmaceuticals in Boston, Mass., for further development leading to human testing. The compounds are expected to enter clinical testing in 2012, Conn says.
"To my knowledge, this is the first example of an academic institution building a coordinated drug discovery effort that is now systematically delivering a pipeline of innovative new drug candidates," Conn tells ddn. "How new models for drug discovery and development will emerge to help stem the current challenges in the pharmaceutical industry has been a major topic of concern. The National Institutes of Health (NIH) is trying to help tackle these issues, but will academic institutions be able to help fill the gap that is being left in early drug discoveries?"
The concept at Vanderbilt began with very basic research funded by the NIH that had implications for new therapeutic approaches, he says.
"The areas we were working on were high-risk and not of great interest to pharma at the time," Conn says. "However, the NIH and the National Institute of Mental Health (NIMH) began to shift their focus to provide mechanisms to develop new tools that could encourage drug discovery."
The NIH then launched the Molecular Libraries Probe Production Network, which supported high-throughput screens of drug-like molecules and limited medicinal chemistry to test new ideas that could lead to new drugs, he says.
"The NIMH then gave us a grant to establish a Vanderbilt National Cooperative Drug Discovery Group focused on discovery of new medicines for treatment of schizophrenia … giving us the funding needed to execute fully integrated drug discovery efforts aimed at fully optimizing new drug candidates for treatment of this disorder," Conn says. "Without strong NIH support, none of these efforts would be possible."
Since Vanderbilt began its drug delivery program in 2003, building from the ground up with veteran pharma-trained drug discovery scientists, "we've had the expertise and time to build a team-based drug discovery effort with all the components found in pharma and with time to establish a culture and approach that allows fully integrated team-based drug discovery research," he says.
At the same time, the pharmaceutical industry has undergone major downsizing because of loss of profits due to major products going off patent and the extremely high risk of drug discovery and development that is resulting in few new drug approvals, Conn says. Thus, there are not enough new products to replace those lost to patent expirations, he adds.
"Although the roots of the problem do not lie exclusively with pharma, we all have to take responsibility that the public trust that has been placed in us to translate advances in basic science into new medicines that clearly improve the standard of patient care," he says. "To me, this is what we in academic drug discovery efforts are all about."