Case Western Reserve University School of Medicine gets $1.25 million to study schizophrenia

Updated 6:49 p.m.

CLEVELAND, Ohio — Three Case Western Reserve University School of Medicine researchers will lead an interdisciplinary team that uses a $1.25 million, four-year, National Institutes of Mental Health grant to study schizophrenia.

It may be the first time in Cleveland that technology capable of retracing human cells back to their primary, or pluripotent, state is used to better understand mental illness, said Paul Tesar, assistant professor in the Department of Genetics and Center for Stem Cell and Regenerative Medicine, who will be responsible for the stem cell portion of the schizophrenia study.

Robert Miller, vice dean for research and the Allen C. Holmes Professor of Neurological Diseases, will be responsible for the nerve and brain portion. And Dr. Robert Findling, the Rocco L. Motto, M.D., Professor of Child & Adolescent Psychiatry at University Hospitals Case Medical Center, will be responsible for the schizophrenia/mental health portion of the study.

The scientists will work together to provide a detailed characterization of brain-cell function in adolescent patients with schizophrenia.

About one percent of the world’s population — that’s nearly 68 million people — has schizophrenia. The serious psychiatric condition causes severe symptoms that expose patients to increased risk for suicide, unemployment, permanent disability and homelessness. Adolescents who develop schizophrenia usually experience more severe symptoms than adults.

“Unfortunately, the cause of schizophrenia is currently unknown and the molecular- and cellular-based mechanisms that contribute to schizophrenia remain undefined,” Miller said in the medical school’s statement. “However, there is a growing body of evidence to suggest that schizophrenia is a neurodevelopmental disorder with genetics being a key risk factor for illness expression.”

That evidence points to unhealthy regulation of cells that produce an insulating coating surrounding nerve cells in schizophrenia sufferers, according to the medical school. The coating, called myelin, is required for the proper conduction of signals along the nerves and in the brain.

But you can’t harvest living brain cells in order to study them. So the scientists plan to use induced pluripotent stem cell (iPS) technology to turn skin cells from affected adolescents into genetically identical stem cells. These primitive cells would be programmed as brain cells and then multiplied for better study, said Tesar, who started working with iPS technology at the National Institutes of Health soon after it was discovered for mice in 2006.

Cleveland’s stem cell center received a $5 million grant from the Ohio Third Frontier in June to help build iPS technology. “This is a new frontier,” Tesar said. “It’s not clear how it’s going to go.”

But studying the reproduced brain cells of schizophrenia patients could help explain how molecular and cellular dysfunctions contributes to their disease.

“We hope to understand the underlying cause of schizophrenia in much greater depth,” Findling said in the medical school statement. “If we can decipher why the cells aren’t functioning properly, we may be able to develop treatments that can restore function to vulnerable patients suffering from schizophrenia.”