When Xconomy first reported the launch of a new biotech company called Karuna Pharmaceuticals in January, the Boston startup declined to reveal much about what it was working on, except to say it had two drug-development initiatives in schizophrenia. Last week, Karuna unveiled one of those programs: a group of compounds that it has licensed from Vanderbilt University in Nashville. The drugs may offer a completely new way of treating schizophrenia—a brain disorder that causes hallucinations, delusions, and a range of social disabilities.
Karuna was incubated at PureTech Ventures, and its CEO is ex-Pfizer executive Ed Harrigan, a neurologist by training. Harrigan is particularly excited about the Vanderbilt compounds because they appear to address all three classes of symptoms that schizophrenia comprises. “Positive symptoms” are hallucinations and delusions, while “negative symptoms” include the inability to experience pleasure or to carry on normal social interactions. Then there are “cognitive symptoms,” such as memory loss. “Current treatments are relatively good at addressing positive symptoms, but there’s a huge need to control the other symptoms, which can be debilitating,” Harrigan says.
Instead of targeting serotonin and dopamine receptors in the brain, as most schizophrenia drugs do, Vanderbilt’s compounds inhibit a protein called glycine transporter one (GlyT1). When this protein runs amuck in the brains of patients, it pumps glycine away from neurons. Blocking that pumping action may have a wide-ranging effect on schizophrenia, says Jeff Conn, a professor of pharmacology and director of the Center for Neuroscience Drug Discovery at Vanderbilt. “We believe it has the potential to address all three major symptom clusters,” he says. “If that’s the case, it would be a breakthrough.”
The Karuna compounds operate in a part of the brain that has become a specialty at Vanderbilt: the “glutamate system,” a network of signals that control memory, learning, and information processing. In 2008, Cambridge, MA-based Seaside Therapeutics awarded the University
