With the help of mouse models, induced pluripotent stem cells (iPSCs), and the “tooth fairy,” researchers at the University of California, San Diego School of Medicine have implicated a new gene in idiopathic or non-syndromic autism. The gene is associated with Rett syndrome, a syndromic form of autism, suggesting that different types of autism spectrum disorder (ASD) may share similar molecular pathways. The findings were published online in Molecular Psychiatry.
“This research is an example of what can be done for cases of non-syndromic autism, which lack a definitive group of identifying symptoms or characteristics,” says principal investigator Alysson Muotri, PhD. “One can take advantage of genomics to map all mutant genes in the patient and then use the patient’s own iPSCs to measure the impact of these mutations in relevant cell types. Moreover, the study of brain cells derived from these iPSCs can reveal potential therapeutic drugs tailored to the individual. It is the rise of personalized medicine for mental/neurological disorders.”
But to effectively exploit iPSCs as a diagnostic tool, Muotri says, researchers “need to compare neurons derived from hundreds or thousands of other autistic individuals.” Enter the “Tooth Fairy Project,” in which parents are encouraged to send researchers a discarded baby tooth from their autistic child. Scientists extract dental pulp cells from the tooth and differentiate them into iPSC-derived neurons for study.
The latest findings are the result of Muotri’s first tooth fairy donor. He and colleagues identified a new disruption in one of the two copies of the TRPC6 gene in iPSC-derived neurons of a non-syndromic autistic child. They confirmed with mouse models that mutations in TRPC6 resulted in altered neuronal development, morphology, and function. They noted that the damaging effects of reduced TRPC6 could be rectified with a treatment of hyperforin, a TRPC6-specific agonist that acts by stimulating the functional TRPC6 in neurons. The researchers also found that MeCP2 levels affect TRPC6 expression. Mutations in the gene MeCP2, which encodes for a protein vital to the normal function of nerve cells, cause Rett syndrome, revealing common pathways among ASD. Read the study abstract.
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