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With new tools, Novartis targets brain disease

Novartis is returning to an area of medical research that has defeated drug companies time and again over the past decade: diseases of the brain — from depression to Parkinson’s — that affect millions of people worldwide.

The Swiss drug giant has relaunched a research group specializing in neuroscience, basing it at its giant research campus in Cambridge and luring a prominent neurobiologist from Stanford University, to take advantage of major new tools that are giving scientists greater insight into how the brain and the diseases that afflict it work.

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“It’s a huge unmet medical need,” said Ricardo E. Dolmetsch, Novartis’s new global head of neuroscience.

Novartis is already on a hiring tear, planning to add 30 neuroscience positions this year and another 70 by the end of next year.

That would give the company some 2,400 employees in Kendall Square, the base for its worldwide research operations. It closed its previous neuroscience operation, based at its Basel, Switzerland, headquarters, in 2011.

Dolmetsch, an expert in autism, said that he is optimistic about the prospects of drug research in these areas because of recent advances in genetics and stem cell science.

Genetics research is teaching scientists more about the mechanisms of brain-based conditions such as autism and attention deficit hyperactivity disorder, he said, and research using stem cells is allowing scientists to model these diseases in a new way — providing laboratory access to human brain cells and networks for the first time.

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Researchers can now take a skin cell from someone with a neurological condition, such as schizophrenia, reprogram the cell into a stem cell, and then transform it into a brain cell.

Then, examining those brain cells from living people in a lab dish should help scientists understand more precisely what goes wrong in different diseases.

They will also be able to make vast quantities of those cells, Dolmetsch said, so they can do early testing to see which drugs might help those cells perform better.

“This is huge,” said Dolmetsch, who pioneered the work while at Stanford University. “We now have this capacity to actually make somebody’s personalized brain cells.”

There have been surprisingly few advances in drug development for neuropsychiatric conditions in the past half-century, said Steven E. Hyman, a Harvard professor in the department of Stem Cell and Regenerative Biology, and director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, a genetics research center.

Largely, the problem has been a lack of understanding of the brain, said Hyman, who collaborates with Novartis and advised the company to reconfigure its neuroscience research to its current setup in Cambridge. He, too, said genetics and stem cell research have the potential to dramatically deepen science’s understanding of the biological conditions behind brain-based conditions.

For example, in 2007, researchers did not know of any genes linked to schizophrenia, Hyman said. Now, they have identified nearly 100, and expect that figure to climb at least sixfold.

“The genetics of schizophrenia, bipolar, and autism are really starting to fall,” he said, opening up more possibilities for drug development.

But finding the genes is not enough, he said. For the new understanding to be meaningful, Hyman said, drug companies must be able to transform these discoveries into effective treatments.

Most of the major drug companies backed away from developing neuroscience drugs earlier this decade, discouraged by their inability to come up with new treatments for depression or more substantive treatments for Alzheimer’s. Drug giants GlaxoSmithKline, AstraZeneca, Sanofi, Pfizer, and Merck have all eliminated or cut back their brain disorder research in recent years, according to published reports.

Hyman said drug companies should resume working on brain conditions because neurological conditions are so pervasive — accounting for nearly 20 to 30 percent of disabilities worldwide — and because companies that wait too long will be at a disadvantage when their competitors find success with new treatments.

Robert H. Ring, chief science officer for the advocacy group Autism Speaks and a former researcher at Pfizer, said he does not think the pharmaceutical industry can continue to ignore neuroscience.

“The demands and the opportunity landscape are just too significant for them to be out of it for too long,” he said.

Ring said he’s pleased Novartis has restarted its neuroscience research and is particularly happy the group is led by an autism expert. There are currently no drugs to treat the underlying communications deficits, social challenges, or repetitive behaviors that define autism.

“I’m enormously excited to see a company with the rich history they have in this area and their interest in genetic disorders heading back into this space,” Ring said.

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