Scientists at the Centre for Addiction and Mental Health have identified a novel drug target that could lead to the development of better antipsychotic medications. Currently, treatment for patients with schizophrenia involves taking medications that block or interfere with the action of the neurotransmitter dopamine, which acts on dopamine D2 receptors in the brain. However, since this D2-blocking action may cause unwanted side effects, such as slow gait, stiffness and tremor, the researchers looked for new ways to interfere with the action of the D2 receptors, without causing side-effects.
The researchers were able to show that the D2 receptor could be combined with a protein called the Disrupted-In-Schizophrenia (DISC1) protein. They found that levels of this combined protein were higher in post-mortem brain tissues of deceased patients with schizophrenia, suggestion it was associated with the illness. Additionally, there were able to identify the regions where the two proteins bound together.
With these findings, the researchers generated a peptide to disrupt the binding of the two proteins, speculating that it may reduce symptoms. In animal models of schizophrenia, they were able to demonstrate that this disruption led to antipsychotic effects, comparable to commonly used antipsychotic medications, but without their side-effects.
“The most exciting aspect of our finding is not the antipsychotic effect of this peptide, which all current antipsychotics have, but rather the possibility of a lack of the side-effects in humans compared to current medications”, says Dr. Fang Liu, Senior Scientist in CAMH’s Campbell Family Mental Health Research Institute and Professor in the Department of Psychiatry, University of Toronto. “We hope that it will lead to a better treatment for schizophrenia patients who experience side-effects from current medications.”
“Our future steps are to determine how this discovery can be translated into a novel treatment for patients as soon as possible,” says Dr. Liu. “We are optimistic that our findings will lead to new and better options for treatment for schizophrenia.”