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$4.5 million to develop glutamate-regulating proteins to improve symptoms of Fragile X, a genetic condition that commonly causes autism. On September 15, Vanderbilt announced it had reached a milestone in that partnership and that drugs could be ready for human testing early next year.
Vanderbilt also has a partnership with the Michael J. Fox Foundation for Parkinson’s Research to develop molecules that act on a specific glutamate receptor. Conn says Vanderbilt is currently in discussions with companies about licensing the Parkinson’s compounds and will “probably announce a partnership by the end of the year.”
All three molecules could be multibillion-dollar opportunities, but the market potential in schizophrenia is particularly large. Sales of Astra Zeneca’s (NYSE: AZN) quetiapine (Seroquel) exceeded $3 billion last year, while Eli Lilly’s (NYSE: LLY) Olanzapine (Zyprexa) brought in $5 billion in revenues. And other companies are looking at the GlyT1 approach, including Roche and Merck (NYSE: MRK).
Harrigan says Karuna was attracted to Vanderbilt’s compounds because they show strong affinity for their targets in the brain and they modulate GlyT1 rather than shutting it down. “We believe that modulation is important to avoid toxicity,” Harrigan says. He adds that the company hopes to bring a drug into clinical trials within two years.
If the Karuna program yields an effective schizophrenia treatment, Conn says, it will bring to full-circle research that started in the 1950s. Back then, scientists noticed that drug abusers on PCP—otherwise known as angel dust—exhibited symptoms similar to schizophrenia. PCP also manipulates the glutamate system, Conn says. “But what we’re trying to do is the opposite of what angel dust does.”
By posting a comment, you agree to our terms and conditions.