Creating a Genetic Model for Autism, with a Little Help from the Tooth Fairy

One of the most complex aspects of autism is that it is not one disease—but many. Known more accurately as the autism spectrum disorder, or ASD, experts have long been trying to tease apart the various ways in which the condition manifests in children, with limited success.

But now, using the latest stem cell technology, scientists at the University of California, San Diego (UCSD) have identified a gene associated with Rett Syndrome—a rare form of autism almost exclusively seen in girls. And in so doing, the team has made the startling discovery that the many types of autism may be linked by common molecular pathways.

The research team, led by UCSD Professor and CIRM grantee Alysson Muotri, explained in a news release how induced pluripotent stem cell, or iPS cell, technology was used to pinpoint a gene associated with Rett Syndrome:

“One can take advantage of genomics to map all mutant genes in the patient and then use their own iPS cells to measure the impact of mutations in relevant cell types. Moreover, the study of brain cells derived from these iPS cells can reveal potential therapeutic drugs tailored to the individual. It is the rise of personalized medicine for mental and neurological disorder.”

iPS cell technology—a process by which scientists transform adult skin cells back into embryonic-like stem cells, after which they can be coaxed into maturing into virtually any type of cell—is a promising way to model diseases at the cellular level. But in order to truly understand what is happening in the brains of people with autism, Muotri and his team needed more samples from autistic individuals—on the order of hundreds or even thousands.

The Tooth Fairy Project allows scientists to gather large quantities of cells from autistic individuals for genomic analysis—simply asking parents to send in a discarded baby tooth.

The Tooth Fairy Project allows scientists to gather large quantities of cells from autistic individuals for genomic analysis—simply by asking parents to send in a discarded baby tooth.

Luckily, Muotri had a little help from the Tooth Fairy.

Or, more accurately, the Tooth Fairy Project, in which parents register for a “Fairy Tooth Kit” that lets them send a discarded baby tooth of their autistic child to researchers. Housed within each baby tooth are cells that can be transformed—with iPS cell technology—into neurons, thus giving the researchers a massive sample size with which to study.

Interestingly, the findings presented here come from the very first tooth to be sent to Muotri. Specifically, the team identified a mutation in the gene TRPC6 was present in children with autism. Additional experiments in animal models revealed that the TRPC6 mutation was indeed associated with abnormal brain cell development and function.

And for their next trick, the team found a way to reverse the mutation’s damaging effects.

By treating the cells with the chemical hyperforin, they were able to restore some normal function to the neurons—offering up a potential therapeutic strategy for treating ASD patients who harbor the TRPC6 mutation.

Drilling down even further, the team found that mutations in another gene called MeCP2, which causes Rett Syndrome, also set off a genetic domino effect that alters the normal function of the TRPC6 gene. Thus connecting this syndrome with other, non-syndromic types of autism.

“Taken together, these findings suggest that TRPC6 is a novel predisposing gene for ASD that may act in a multiple-hit model,” said Muotri. “This is the first study to use iPS cell-derived human neurons to model non-syndromic ASD and illustrate the potential of modeling genetically complex sporadic diseases using such cells.”

Find out more about how stem cell research could help solve the mysteries behind autism in our Autism Fact Sheet.

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