Fragile X Drug Success In Mice Gives Hope For Autism Treatment

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Scientists have found a compound that can reverse the major symptoms of Fragile X syndrome -- the most commonly inherited form of mental disability in boys and a known cause of autism -- in adult mice.

The results are a good omen for similar drugs in the development pipeline aimed at treating humans.

A research team led by scientists from the Massachusetts Institute of Technology and Swiss pharmaceutical giant Roche described their findings on Wednesday in the journal Neuron. Roche is one of three companies that are clinically testing drugs similar to the compound described in the paper.

Fragile X syndrome is more likely to affect boys because the gene in question, FMR1, resides on the X chromosome. Since males only have one X chromosome, they aren't as able to mask the effects of the faulty gene as females. Patients with the syndrome can suffer from a variety of symptoms, including anxiety, memory and learning problems, and hyperactivity.

In the current study, the researchers focused on mGlu5, a receptor for the neurotransmitter glutamate.

MIT neuroscientist professor Mark Bear, a co-author of the paper, has done previous work linking Fragile X syndrome to this receptor. He likens the situation to a problem with a molecular machine in the synapses - the spaces between neurons.

While mGlu5 acts as an accelerator on this machine, the gene that's mutated in Fragile X encodes the brake, Bear says. When that brake is flawed or gone, mGlu5 is unchecked and the machine goes into overdrive, making more proteins in the synapses and weakening connections between neurons.

Bear and his colleagues gave a compound called CTEP, which inhibits the mGlu5 receptor, to mature mice bred specially to provide a model for Fragile X syndrome in order to try and put the brakes back on the process.

CTEP treatment corrected a wide range of Fragile X syndrome symptoms in the mice, including memory deficits and hypersensitivity to sound, as well as morphological changes- such as overly large testicles - characteristic of the disease, according to senior author and Roche researcher Lothar Lindemann.

The most important implications of our study are that many aspects of [Fragile X syndrome] are not caused by an irreversible disruption of brain development, and that correction of the altered glutamate signaling can provide widespread therapeutic benefit, Lindemann said in a statement Wednesday.

Bear says the results are heartening, but that researchers have to go forward cautiously.

There's a lot of anticipation that the insights that we gain by studying Fragile X might apply to autism more generally, Bear said.

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