Drug Rescue and Repurposing: Allan S. Kaplan
By: Allan S. Kaplan
Which drug is being investigated for its repurposing potential?
Olanzapine (Zyprexa) is being investigated for its repurposing potential. It has Health Canada approval for the treatment of schizophrenia and bipolar disorder.
For what new purpose is the drug being studied?
The drug is being studied in the context of anorexia nervosa. Currently, there are no evidence based treatments for adults with anorexia nervosa, a serious psychiatric disorder with the highest mortality among psychiatric illnesses of approximately 15%. Anorexia nervosa is the only psychiatric disorder for which there is no Health Canada or U.S. Food and Drug Administration (FDA) approved drug. Olanzapine, among its other effects, has affinity for dopaminergic receptors in the brain, acting primarily to block the brain chemical, dopamine. The core disturbances in anorexia nervosa include disturbances in reward (anhedonia), activity (compulsive/excessive exercising), regulating intense negative feelings (affective regulation), and the interpretation of bodily sensations (enteroceptive awareness). All of these functions are known to be mediated by dopamine.
What are the research findings?
My colleagues and I are conducting a National Institute of Mental Health (NIMH)-funded, multisite, randomized, placebo-controlled clinical trial evaluating the effectiveness of olanzapine compared to placebo in 200 outpatients acutely ill with anorexia nervosa. My colleagues at the Centre for Addiction and Mental Health (CAMH) Neurogenetics Laboratory and I are also conducting a pharmacogenetics study as part of this trial, examining genes that are known to predict weight gain in the subjects in this trial. In a pilot study involving 25 subjects, 13 of whom were assigned to olanzapine, there was a statistically different rate of weight gain in subjects assigned to olazanpine compared to placebo. The drug was well tolerated and no serious side effects were noted.
What do you hope is the future of the drug in this field?
With the results of the pharmacogenetic aspect of this study, the hope is that we can identify those subjects whose genetics would predict a positive response to this drug as we move to personalized medicine in psychiatry. As such, it is hoped that olanzapine can be a useful adjunctive treatment for select patients with anorexia nervosa.
What do you think is the future of drug rescue and repurposing?
Many pharmaceutical companies are moving away from developing new central nervous system (CNS) drugs and psychiatric drugs in particular, due to the high costs of drug development, the absence of good animal models for psychiatric disorders, and low success rates in phase 3 clinical trials. As a result, the CNS pipeline is drying up and drug repurposing becomes an important and valuable research approach to being able to develop new drug treatments in a cost effective manner—not just for psychiatry but for other areas of medicine as well.
Allan S. Kaplan MSc MD FRCP(C)
Director, Institute of Medical Science
Chief of Clinical Research and Senior Scientist Campbell Research Institute
Centre for Addiction and Mental Health
Senior Scientist, Toronto General Research Institute
Vice Chair, Research, Department of Psychiatry
Professor of Psychiatry