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Drug treatment possible for reversing autism

Posted by on Nov. 25, 2012 at 1:25 PM
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Drug treatment possible for reversing autism

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Researchers have found a critical and previously unknown link between synthesis of brain proteins and autism spectrum disorders that they say could lead to new treatments. In their studies, scientists were able to reverse ASD behaviors in mice by manipulating brain cell signals, which could lead to the development of drugs to reverse ASD associated behaviors.

McGill University scientists explain mouse studies show symptoms that develop and associated with ASD are the result of abnormally high synthesis of a group of proteins called neuroligins.

Neuroligins are molecules that are involved in sending brain signals. The molecules bind with a ligand (another group of molecules or ions) to transmit and process information in the brain.

Prof. Nahum Sonenberg, from McGill’s Dept. of Biochemistry, Faculty of Medicine, and the Goodman Cancer Research Centre explained in a press release: “We used a mouse model in which a key gene controlling initiation of protein synthesis was deleted.

In these mice, production of neuroligins was increased. Neuroligins are important for the formation and regulation of connections known as synapses between neuronal cells in the brain and essential for the maintenance of the balance in the transmission of information from neuron to neuron.”

When the researchers blocked synthesis of the proteins with gene therapy they were able to reverse autism like behaviors.

Christos Gkogkas, a postdoctoral fellow at McGill and lead author. “Our work is the first to link translational control of neuroligins with altered synaptic function and autism-like behaviors in mice.

Neuroligin mutation was first discovered in 2003 and linked to autism spectrum disorders, but research hasn’t uncovered the exact mechanism of how the mutations lead to ASD symptoms.

Gkogkas said the researchers reversed autism symptom in mice using existing compounds developed for cancer treatment that reduce protein synthesis. Next they used non-replicating viruses to halt the abnormal synthesis of neuroligins.

The scientists used a computer algorithm to identify structure and regulation of mRNA of neuroligins. They discovered that abnormal synthesis of the proteins is what causes imbalance in single brain cell signals.

The autistic behaviours in mice were prevented by selectively reducing the synthesis of one type of neuroligin and reversing the changes in synaptic excitation in cells,” explained Prof. Jean-Claude Lacaille at the University of Montreal’s Groupe de Recherche sur le Système Nerveux Central and Department of Physiology in a media release.

In other words, he says, the scientists manipulated brain cell signals to see how it affected behavior in the mice. When they manipulated a second neuroligin they were able to reverse autistic behaviors.

“The fact that the balance can be affected suggests that there could be a potential for pharmacological intervention by targeting these mechanisms,” Lacaille concluded.

But Sonenberg cautions that the finding doesn't mean a treatment for autism is close at hand. . “The drug we used would be too toxic to use for ASDs,” he says. “But we’ve shown that this pathway is important, identified potential therapeutic targets and demonstrated that a drug therapy is possible in principle.”

The finding suggests new hope for treating autism spectrum disorders with drugs that block abnormally high synthesis of neuroligins in the brain associated with ASD that affects 1 in 88 children across every ethnic, racial and socioeconomic group, according to statistics from the CDC.

Source:
Journal Nature
November 21, 2012

by on Nov. 25, 2012 at 1:25 PM
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