Dec. 9, 2014 – Scientists at the Centre for Addiction and Mental Health (CAMH)
have identified a novel drug target that could lead to the development of
better antipsychotic medications.
Dr. Fang Liu, senior scientist in CAMH’s Campbell Family
Mental Health Research Institute and professor in the Department of Psychiatry,
University of Toronto, and her team published their
results online in the journal Neuron.
Dr. Fang Liu
Current 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, because this D2-blocking action may cause unwanted side-effects, such
as slow gait, stiffness and tremor, Dr. Liu and her team looked for new ways to
interfere with the action of D2 receptors, without causing these side-effects.
Dr. Liu and colleagues showed that the D2 receptor could
combine with a protein called the Disrupted-In-Schizophrenia (DISC1) protein. Then,
they showed that levels of this combined protein were higher in post-mortem
brain tissues of deceased patients with schizophrenia, suggesting it was
associated with the illness. Delving even further, the researchers identified
the regions where the two proteins bound together.
With this information, they were able to generate 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. Liu. “We hope that it will lead to a better
treatment for schizophrenia patients who experience side-effects from current
medications.” These side-effects
discourage some patients from taking their medications, which impacts recovery.
Schizophrenia is a chronic, often severe and disabling mental illness that
affects one percent of the general population.
“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.”
This study was funded by the Canadian Institutes of Health
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The Centre for Addiction and Mental Health (CAMH) is Canada's largest mental health and
addiction teaching hospital and a world leading research centre in this field.
CAMH combines clinical care, research, education, policy development and health
promotion to help transform the lives of people affected by mental illness and
addiction. CAMH is fully affiliated with the University of Toronto,
and is a Pan American Health Organization/World Health Organization
Collaborating Centre. For more information, please visit www.camh.ca
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