Fragile X reversed in adult mice

Research Update:

Study used used compound that inhibits mGluR5 to correct signs of Fragile X

The work was done by a team led by Dr. Lothar Lindemann at Roche, and a group led by Dr. Mark Bear at MIT.

A recent study finds that a new compound reverses many of the major symptoms associated with Fragile X syndrome (FXS), the most common form of inherited intellectual disability and a leading cause of autism. The paper is published in the April 12 issue of the journal Neuron, describes the exciting observation that the FXS correction can occur in adult mice, after the symptoms of the condition have already been established.

Previous research has suggested that inhibition of mGlu5, a subtype of receptor for the excitatory neurotransmitter glutamate, may ameliorate many of the major symptoms of the disease.

This study, a collaboration between a group at Roche in Switzerland, led by Dr. Lothar Lindemann, and Dr. Mark Bear’s MIT lab, used an mGlu5 inhibitor called CTEP to examine whether inhibition of mGlu5 could reverse FXS symptoms.

The researchers gave CTEP to mice which model Fragile X. “We found that even when treatment with CTEP was started in adult mice, it reduced a wide range of FXS symptoms, including learning and memory deficits and auditory hypersensitivity, as well as morphological changes and signaling abnormalities characteristic of the disease,” reports Dr. Lindemann.

“The most important implications of our study are that many aspects of FXS are not caused by an irreversible disruption of brain development, and that correction of the altered glutamate signaling can provide widespread therapeutic benefit,” explains Dr. Bear.

“It will be of great interest to see whether treatment of FXS in human patients can be addressed in a similar broad fashion and with a similar magnitude as was suggested by our preclinical data,” conclude Dr. Lindemann and Dr. Bear. “We anticipate that disturbed signaling can be corrected with other small molecule therapies targeting mGlu5 that are currently being used in human clinical trials.”

Read the paper Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice.


Trials with compounds that inhibit mGluR5 are accepting patients with Fragile X

Clinical trials for children and adults with Fragile X are underway right now, based on an impressive series of studies by many labs of the Fragile X — mGluR5 connection.

Novartis and Roche have each developed their own mGluR5 antagonist to treat Fragile X Syndrome, and both companies are accepting participants with Fragile X in their trials.

Find out more about Fragile X treatment trials here

The Novartis compound, AFQ056, is scheduled to be filed with the FDA in 2013 for treatment of Fragile X, and in 2014 for treatment of Parkinsons disease. See the filings here.