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Indian researchers from NCBS offer drug leads to reverse defects of autism, mental retardation

Wednesday, June 23, 2010, 15:56 This news item was posted in Discoveries category and has 0 Comments so far.

Indian researchers have identified certain methods to reverse defects in the brain that could lead to behavioural disorders like autism and mental retardation.

Researchers of National Centre for Biological Sciences (NCBS), Bangalore have successfully tested potential drugs to reverse certain defects identified in an area of the brain which leads to debilitating emotional symptoms of Fragile X Syndrome (FXS).

FXS is considered a leading genetic cause of autism and mental retardation.

People suffering from Fragile X Syndrome (FXS), which is a mutation in a gene on the X chromosome, suffer from learning disabilities, attention deficit, seizures, anxiety and mood instability.

Some of these disabilities could be rectified by reversing the synaptic deficits in the brain using drugs, the researchers found.

When used in adult mice that were genetically engineered to model FXS, the experimental drug was found capable of reversing the synaptic defects in the neurons in an area of brain called amygdala.

Amygdala, which is a small, almond-shaped part of the brain. The region is known to mediate emotion influence on memory which is affected in FXS model mice.

To assess the cellular and molecular basis for the emotional problems associated with FXS, the researchers studied neurons and synapses in the amygdala.

Electrophysiological recordings from neurons in the amygdala of the mice found that there were defects on both sides of synapses in the amygdala.
The neurons were not properly communicating with each other. Together, these deficits impair the ability of neurons in the amygdala to communicate and encode information.

While looking for ways to normalize communication between neurons, the researchers attention was caught in Group I metabotropic glutmate receptors (mGluRs), which has been implicated in synaptic dysfunction in other brain areas in FXS.

By blocking specific receptors, the drug could restore he functionality of receptors and certain aspects of normal communication between neurons.

These findings open up a new avenue to explore therapeutic substance to treat and even reverse conditions like autism and mental retardation for which no known cure exists hitherto, believes Prof Sumantra Chattarji, National Centre for Biological Sciences, who led the year-long research.

They have potential therapeutic significance because it showed that even a relatively brief pharmacological treatment is capable of correcting some of these defects in mice.
Synaptic defects can be corrected pharmacologically even after the disease alters the brains of the FXS mice, the study has now shown.

The study was a collaborative effort between NCBS and New York University (NYU). The grants came in from multiple sources including FRAXA Research Foundation, National Institutes of Health, Pfizer Asia R&D Collaborative Grant and NCBS.

“We are open to collaborations with pharma companies to investigate these important issues, especially with newer and more potent compounds. For instance, we already have an ongoing collaboration with the Autism Unit at Pfizer, Groton, CT, USA,” Prof Chatarji was quoted as saying.

Prof Chatarji’s team is now in the process of assessing if the mGluR blockers would be effective irrespective of age.

Prof Chatarji’s lab is also working to unlock cellular and molecular mechanisms of anxiety, depression and post-traumatic stress disorder for which its collaborations with Pfizer, USA and Servier, France are notable in this connection.

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