A new study has identified biomarkers that may help in the development of better treatments for schizophrenia. The findings are published online in JAMA Psychiatry.
In the past two decades, the pharmaceutical industry has spent over $2.5 billion in the ongoing effort to develop better schizophrenia medications. But while some of these drugs appear to be effective in animal models, most fail when tested in late-stage human clinical trials.
“While a great deal of money has been invested in developing schizophrenia drugs, a similar investment hasn’t been made to develop biomarkers that could improve the reliability and consistency of test results,” said Daniel Javitt, M.D., Ph.D., professor of psychiatry and Director of the Division of Experimental Therapeutics at Columbia University Medical Center (CUMC).
A new proposal called the FAST Initiative was established by the National Institute of Mental Health to validate the use of biomarkers to facilitate drug development. The initiative aligns with the 21st Century Cures Act passed last year by Congress which authorized the U.S. Food and Drug Administration (FDA) to approve treatments based on biomarker data alone, and created a formal Biomarker Qualification Program.
During the research, FAST-Psychosis scientists identified biomarkers using MRI applications to support the development of drugs that target the glutamate system. Previous research has shown that drugs such as phencyclidine (PCP or “angel dust”) and ketamine, which block glutamate receptors, cause schizophrenia-like symptoms in healthy volunteers.
Therefore, the researchers analyzed three potential biomarkers for detecting the effects of ketamine on human brain function. One of the most significant biomarkers involved an increase in blood flow in the brain’s frontal regions detected consistently among participants who were briefly exposed to ketamine. It also reliably distinguished them from those who had been given a placebo.
Another measure of the concentration of glutamate/glutamine was also sensitive to ketamine brain effects. Overall, the biomarkers were successful in identifying over 90 percent of participants who had been given ketamine, and differentiating them from all of those in the placebo group.
“These results enable us to determine whether potential treatments will be effective against patients’ symptoms by testing them first in healthy volunteers and defining the best doses based on objective physiological data before conducting costly clinical trials,” said Jeffrey Lieberman, M.D., the Lawrence C. Kolb Professor and Chairman of the Department of Psychiatry at CUMC, and principal investigator of this study.
If the biomarkers are approved by the FDA, the study findings will be the first objective biomarkers registered to permit approval of new glutamate-modulating treatments for schizophrenia.