Drug Blocks Development of Autism Trigger in Stem Cells

Researchers from Weill Cornell Medical College have demonstrated the most common genetic form of mental retardation and autism occurs as a result of a mechanism that shuts off the gene associated with the disease.

Their study results published in Science magazine also show a drug that blocks this mechanism can prevent fragile X syndrome, which suggests similar drug therapies are possible for other mental illnesses.

Using stem cells from fragile X-positive human embryos, the scientists learned that until 11 weeks of gestational development, messenger RNA begins to duplicate with the fragile X gene. This gene prevents the DNA from producing normal proteins that facilitate signals between brain cells. Fragile X, which occurs most often in boys, causes intellectual disabilities and displays physical, behavioral, and emotional traits.

“Then, all of a sudden it turns off, and stays off for the rest of the patient's lifetime, causing fragile X syndrome,” Samie Jaffrey, MD, PhD, a professor of pharmacology at Weill Cornell Medical College and the study’s senior author, said in a press release. “But scientists have not understood why this gene gets shut off. We discovered that the messenger RNA can jam up one strand of the gene's DNA, shutting down the gene — which was not known before.”

The researchers took it one step further by coaxing the stem cells into becoming brain neurons, and then treating them before the shut-off point with a drug developed to keep the gene-producing protein.

In response their success, the researchers are now looking for other RNA-DNA duplexes in other trinucleotide repeat diseases, such as Huntington’s disease, mytotrophic dystrophy 1 and 2, Friedrich’s ataxia, Jacobsen syndrome, familial amyotrophic lateral sclerosis, and others.