Online Extra: Hunting the Genes of Mental Illness

The two leaders of Psychiatric Genomics explain their quest to fathom the genetic basis of manic depression, autism, and schizophrenia

Psychiatric Genomics Inc. is applying cutting-edge biotechnology to diseases of the brain. By using the principles of systems biology -- the study of entire disease pathways -- the privately held Gaithersburg (Md.) company is hoping to find new treatments for manic depression, schizophrenia, and autism. Its approach is a departure from the traditional method of studying one gene at a time.

CEO Richard E. Chipkin, a veteran of Schering-Plough Corp. (SGP ), and Chief Scientific Officer Michael Palfreyman, who has a PhD in neuroscience, have almost a half-century of experience in the biotech industry between them. The two recently spoke with BusinessWeek Correspondent Arlene Weintraub about the challenge of developing drugs to treat mental illnesses and the outside-the-box strategy their three-year-old startup is taking. Edited excerpts of their conversation follow:

Q: Explain your company's approach to drug development.


Mental disorders are complex. We know that multiple genes and environmental components come together to cause them. What we're trying to do is take the thousands of genes we know have changed in a diseased brain and align them so we understand how they are related.

Q: Why did you choose to focus on manic depression, autism, and schizophrenia?


We know there's a very strong genetic link in each of those diseases. And there's a large unmet need out there. Most of the drugs used today were found by serendipity, without anyone really understanding the diseases.

Q: What's wrong with today's treatments?


Take schizophrenia. The drugs have side effects and limited efficacy. They have this curious delayed onset. And 20% of the patients become resistant to the treatment. It's a real problem that ends up causing homelessness and suicide.

Q: How does your research method differ from traditional methods for studying these diseases?


We're going in not knowing exactly what we're looking for. We know in general we're looking for genes that are activated or deactivated in diseases. We're looking for patterns of similar genetic changes among multiple patients. That will help us get down to the fundamental mechanics -- the causes -- that until recently were impossible to find.

Q: What are some of your unique challenges?


Obtaining brain tissue from deceased patients for studies has been very hard. It has to be high quality. And we have to follow strict ethical guidelines. We have to try to get a good understanding of the patient's condition without his or her identity being revealed.

Access to medical records is key. Not many brain banks are up to the task. We've had to form a new kind of interface between science and patient-advocacy groups. This research depends on the generosity of patients' families.

Q: What will be the genomics payoff in mental illness?


It's an incredibly exciting time. For the first time we can find real root causes for these diseases.

Edited by Patricia O'Connell

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