Vanderbilt forges path for academia

University licenses compounds showing promise for Parkinson’s disease, schizophrenia and Fragile X syndrome

November 7, 2011
Lori Lesko
NASHVILLE, Tenn.—Directing a combination of team scienceculture, infrastructure, business expertise and can-do spirit towardsystematically delivering novel drug candidates to treat serious braindisorders, Vanderbilt University is not only providing an unmet need, but alsoforging a path for other academic institutions to follow.
 
 
"There is a crying need for better drugs to treat peoplewith serious brain disorders, such as Parkinson's disease and schizophrenia—andfor better ways to treat children with autism," says Jeffrey Conn, director ofthe Vanderbilt Center for Neuroscience Drug Discovery (VCNDD).
 
 
Just last month, Vanderbilt announced new therapies forParkinson's disease, schizophrenia and Fragile X syndrome, a direct result ofits plan to bring new drugs to market. The new Vanderbilt compounds, developedwith support from the Michael J. Fox Foundation for Parkinson's Research(MJFF), bypass the dopamine system altogether and instead modulate the activityof a specific glutamate receptor called mGlu4.
Research suggests that excessive signaling through anotherglutamate receptor, mGluR5, may contribute to manifestations of Fragile Xsyndrome, which include impaired cognitive function, developmental delay,attention deficit and hyperactivity, anxiety, obsessive-compulsive and autisticbehaviors.
 
 
With support from the company, the Vanderbilt researchershave developed drug candidates that may improve Fragile X symptoms by "tuningdown" the mGluR5 activity. Conn and his team have also identified chemicalcompounds that work in a fundamentally different way, by inhibiting glycinetransporter one (GlyT1). This allows for more normal function of brain cellsinvolved in schizophrenia.
 
 
In a transaction announced this month, Vanderbilt licensedthe compounds to Karuna Pharmaceuticals in Boston, Mass., for furtherdevelopment leading to human testing. The compounds are expected to enterclinical testing in 2012, Conn says.
 
"To my knowledge, this is the first example of an academic institutionbuilding a coordinated drug discovery effort that is now systematicallydelivering a pipeline of innovative new drug candidates," Conn tells ddn. "How new models for drug discoveryand development will emerge to help stem the current challenges in thepharmaceutical industry has been a major topic of concern. The NationalInstitutes of Health (NIH) is trying to help tackle these issues, but willacademic institutions be able to help fill the gap that is being left in earlydrug discoveries?"
 
 
The concept at Vanderbilt began with very basic researchfunded by the NIH that had implications for new therapeutic approaches, hesays.
 
 
"The areas we were working on were high-risk and not ofgreat interest to pharma at the time," Conn says. "However, the NIH and theNational Institute of Mental Health (NIMH) began to shift their focus toprovide mechanisms to develop new tools that could encourage drug discovery."
 
 
The NIH then launched the Molecular Libraries ProbeProduction Network, which supported high-throughput screens of drug-likemolecules and limited medicinal chemistry to test new ideas that could lead tonew drugs, he says.
 
 
"The NIMH then gave us a grant to establish a VanderbiltNational Cooperative Drug Discovery Group focused on discovery of new medicinesfor treatment of schizophrenia … giving us the funding needed to execute fullyintegrated drug discovery efforts aimed at fully optimizing new drug candidatesfor treatment of this disorder," Conn says. "Without strong NIH support, noneof these efforts would be possible."
 
 
Since Vanderbilt began its drug delivery program in 2003,building from the ground up with veteran pharma-trained drug discoveryscientists, "we've had the expertise and time to build a team-based drugdiscovery effort with all the components found in pharma and with time toestablish a culture and approach that allows fully integrated team-based drugdiscovery research," he says.
 
At the same time, the pharmaceutical industry has undergonemajor downsizing because of loss of profits due to major products going offpatent and the extremely high risk of drug discovery and development that isresulting in few new drug approvals, Conn says. Thus, there are not enough newproducts to replace those lost to patent expirations, he adds.
 
"Although the roots of the problem do not lie exclusivelywith pharma, we all have to take responsibility that the public trust that hasbeen placed in us to translate advances in basic science into new medicinesthat clearly improve the standard of patient care," he says. "To me, this iswhat we in academic drug discovery efforts are all about."
 
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