Scientists have discovered how the gene mutation responsible for fragile X syndrome - the most common inherited form of mental retardation - alters the way brain cells communicate.
In neurons cultured from laboratory rats, the scientists also were able to reverse the effects of the mutation using a drug targeted to the specific site in an upstream pathway of the defect. The finding could lead to the development of human therapies for this previously untreatable condition.
The research was led by Stephen T. Warren, PhD, Timmie professor and chair of human genetics in Emory University School of Medicine, and Gary J. Bassell, PhD, Emory professor of cell biology. It will be reported in the Proceedings of the National Academy of Sciences (PNAS) the week of Sept. 17. Lead author is Emory genetics postdoctoral fellow Mika Nakamoto.
"We have now explained the fundamental defect in the brain in fragile X syndrome and, most importantly, found that we can correct this problem in the laboratory," says Dr. Warren. "This is quite exciting, progressing from the identification of the gene in 1991 to now believing we will be able to treat a previously untreatable condition. Our next steps will be to continue screening and identifying the best drugs to try and correct the deficiencies that result from fragile X syndrome."
Fragile X syndrome is caused by a mutation in the FMR1 gene on the X chromosome. A region of the mutated FMR1 gene repeats a trinucleotide sequence of DNA bases--CGG--between 200 and 1,000 times, rather than the normal 6 to 55 repeats in normal individuals. The abnormal trinucleotide repeats cause the absence of the FMR protein normally produced by the gene.
Dr. Warren and his colleagues led an international team that discovered the FMR1 gene in 1991. They later characterized the FMR protein (FMRP) and developed diagnostic tests for fragile X syndrome. Ever since, their research has focused on identifying the specific consequences of FMRP deficiency in the brain and finding targets for drug therapy.