Human induced pluripotent stem cells (top left) can be coaxed to become neural progenitor cells (top right) and then neurons (bottom) for modeling human brain development and psychiatric disorders.
A new, $15.4 million national collaboration between four academic research centers and two pharmaceutical industry partners aims to develop new ways to study and screen drugs to treat schizophrenia and bipolar disorder.
The National Institute of Mental Health formed and funded the consortium that includes government, academic and industry researchers to use induced pluripotent stem cell (iPSC) technology — a type of stem cell that can be generated from adult stem cells — to find better treatments for the two psychiatric conditions.
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Rusty Gage, professor at the Laboratory of Genetics at the LaJolla, California-based Salk Institute for Biological Studies, and Hongjun Song, professor of neurology and neurosciences at the Johns Hopkins University School of Medicine in Baltimore, will lead the five-year project aimed at accelerating new methods of screening drugs proven effective against the mental illnesses, which affect more than eight million Americans.
According to the NIMH, current drugs for bipolar disease only treat manic or depressive swings, but not both. And little is known about the underlying causes of schizophrenia.
Other academic partners include the University of Michigan in Ann Arbor and the Sanford Burnham Prebys Medical Discovery Institute, also of La Jolla. Janssen Research & Development, a division of Johnson & Johnson’s Janssen Pharmaceutica of Raritan, New Jersey, and Cellular Dynamics International, of Madison, Wisconsin, are the industry partners.
The consortium will use iPSC technology to study donated skin cells from more than 50 patients with schizophrenia and bipolar disease. They will convert those cells into neurons and other brain cell types to study the genetic and other underlying mechanisms of the diseases.
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The NIMH’s National Cooperative Reprogrammed Cell Research Groups program is funding the project. Researchers said they hope to gather and disseminate large bodies of data illuminating the molecular and genetic differences between bipolar disorder and schizophrenia.
Johns Hopkins’ Song said stem cells hold tremendous potential in the search for treatments and cures of disease, but noted that there has been a bottleneck in stem cell research. Song said every lab uses different protocols and cells from different patients, making it difficult to compare results.
“For years we’ve seen so much variability in the way that different laboratories perform research,” he said. “Everyone has been doing their own thing.”
He said this collaboration gathers the resources needed to create robust, reproducible tests used to develop new drugs for mental health disorders.
“The next phase is to translate this into a clinical development, a drug or treatment,” said Song, who pointed out the consortium set six-month milestones to accomplish its goals.
“There are hard, planned deadlines. Our goal is to release our research regularly, to publish and push out the results every year and to translate what we have learned and bring these discoveries to market,” he said.
Sue O’Shea, a professor and the director of the University of Michigan’s Pluripotent Stem Cell Core, said now there is no effective way to study mental disorders like schizophrenia and bipolar disease. “But for the first time, we’ll be able to take skin cells and convert those into neurons.”
O’Shea said besides standardizing the assays used to identify iPSCs, the consortium hopes to expand the power and reach of its research.
The Salk Institute’s Gage said the collaboration planned for potential overlap. “Clearly defined roles and leads, as well as frequent and open communications between all of the collaborators, will ensure that there is no unnecessary duplication of efforts. In addition, defined methods for data sharing and encouragement to replicate others’ findings will be a critical part of working efficiently,” he said.
He said each academic group has a particular question they are addressing, but will share many of the tools and techniques, which will maximize cooperation and consensus-building. Johns Hopkins will lead schizophrenia efforts, while the Salk Institute will direct bipolar disorder research, but all will all share technology, methodology and protocols.
While Gage said the partners have formulated a detailed timeline for the initiative’s deliverables, he cautioned: “It is clear that some flexibility will be needed as we are dealing with human biology and disease and there are still many unknowns.”
Image: Zhexing Wen and Guo-li Ming, Johns Hopkins University
