FRAXA Research Foundation Announces That Massachusetts Institute of Technology (MIT) Researchers Have Reversed Key Symptoms in an Important Animal Model of Mental Retardation and Autism

NEWBURYPORT, Mass., June 26 /PRNewswire/ -- "Our study suggests that inhibiting a certain enzyme in the brain could be an effective therapy for countering the debilitating symptoms of Fragile X Syndrome (FXS) in children, and possibly in autistic kids as well," said co-author Mansuo L. Hayashi, a former MIT Picower Institute postdoctoral fellow, currently at Merck Research Laboratories in Boston.

The international team of researchers, led by MIT Nobel laureate Susumu Tonegawa, will release their report this week in the early online edition of the Proceedings of the National Academy of Sciences (PNAS).

The study identifies a key enzyme as a possible target for an FXS drug. PAK, p21-activated kinase, affects the number, size and shape of connections between neurons in the brain. These connections are formed by small protrusions called "spines" on branches of neurons called "dendrites". The numbers and shapes of dendritic spines are crucial for normal brain function. FXS patients have more dendritic spines, but each spine is longer and thinner than in non-affected individuals. According to analysis done by Sumantra Chattarji and Shankar Rao, co-authors based in Bangalore, India, inhibition of PAK in the genetically manipulated Fragile X mouse model helped reverse the abnormalities in spine number and structure.

"Strikingly, PAK inhibition also restored electrical communication between neurons in the brains of the FXS mice, correcting their behavioral abnormalities in the process," said co-author Susumu Tonegawa, 1987 Nobel laureate and Picower Professor of Biology and Neuroscience. There are known chemical compounds that inhibit the enzymatic activity of PAK. These compounds or versions of them may be useful in the development of drugs for treating FXS, he said.

Fragile X is caused when a single gene fails to produce a protein necessary for normal brain development. According to the CDC, FXS affects 1 in 4,000 males and 1 in 6,000 females worldwide. Estimates of autism prevalence ranges from 1 in 500 to 1 in 150 children. There is no effective treatment for FXS and other types of autism.

FRAXA Medical Director, Dr. Michael Tranfaglia said, "This is an exciting finding, because PAK inhibition is a completely new therapeutic strategy for fragile X. Previous studies have shown similar potential for drugs which block metabotropic glutamate receptors, but PAK is not directly involved in this pathway. Additionally, many other developmental disorders share the dendritic abnormalities which are rescued by PAK inhibition, so this may be an effective strategy for treating conditions like autism."

This work was supported by FRAXA Research Foundation, the Simons Foundation, and NIH.

FRAXA Research Foundation funds research to find effective treatments and a cure for Fragile X. For more information, please contact Dr. Tranfaglia at fraxa@comcast.net , or visit the FRAXA website http://www.fraxa.org.

CONTACT: Katie Clapp of FRAXA Research Foundation, +1-978-462-1866

Web site: http://www.fraxa.org//