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FRANÇAIS

Novel therapeutic strategies to repair brain abnormalities in psychiatric disorders

Team
Team leader: Dr. Yu Tian Wang, University of British Columbia
Members: Dr. Stephen S.G. Ferguson, University of Western Ontario; Dr. Alaa El-Husseini, University of British Columbia; Dr. Ridha Joober, McGill University; Dr. Anthony G. Phillips, University of British Columbia

Project Overview
Communication between brain cells is essential for normal brain function. Healthy brain cells are controlled through chemical messengers that stimulate or inhibit brain activity. Current theories indicate that psychiatric disorders such as addiction, schizophrenia, autism and mental retardation evolve from an imbalance of these chemical messengers leading to a disruption in the way brain cells are able to communicate with each other.

Drugs currently available for the treatment of psychiatric disorders often target multiple receptors throughout the brain. Although these compounds have therapeutic efficacy in subgroups of patients, negative side effects often develop which limit their use. Accordingly, new Pharmacotherapies, designed to target more specific brain processes implicated in various aspects of psychiatric illness, are urgently needed.

Dr. Wang and his team investigated a novel method for treating these disorders, whereby small peptides can target specific sub-cellular processes that disrupt the balance of chemical messengers and hence the normal communication between brain cells. Dysfunction of the normal communication between brain cells has been linked to psychiatric diseases and this new class of drugs is designed to restore normal function in a highly specific manner that will minimize negative side effects. The team’s initial focus was on developing a therapy for drug addiction, however the principles underlying the action of these new drugs could lead to the development of similar treatments for other neurological and neuropsychiatric illnesses, such as Alzheimer’s disease, autism, mental retardation and schizophrenia.

Findings
Communication between brain cells is essential for normal brain function. Disruption of this process has been proposed as the root cause of many psychiatric disorders including addiction, schizophrenia, autism and mental retardation. Most of the current drug therapies for these disorders work in an unspecific manner, repairing the communication in the whole brain. While lessening symptoms, they often lead to a host of negative side effects. This team completed a Proof of Principle study for developing a novel method for treating these disorders, whereby drugs can target the specific processes in brain cells in need of repair, and restore the normal brain function, with no obvious negative side effects.

Impact
Results from this investigation can lead to the development of drugs that have no side effects, thereby giving a better quality of life to patients affected by neurological and psychiatric disorders such as addiction, Alzheimer’s disease, autism, mental retardation and schizophrenia.

Publications
June 25, 2007 Nature NeuroScience -
Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment

February 16, 2006 Neuron 
A Preformed Complex of Postsynaptic Proteins Is Involved in Excitatory Synapse Development
 

November 25, 2005 Science  
Nucleus Accumbens Long-Term Depression and the Expression of Behavioral Sensitization