A newly published study of autism sheds a glimmer of light on how some patients with autism spectrum disorder (ASD) and related illnesses may be diagnosed and perhaps even treated in the future.

As reported November 11th in Molecular Psychiatry, a team led by 2014 NARSAD Independent Investigator Grantee Alysson R. Muotri, Ph.D., of the University of California, San Diego (UCSD) sampled cells from a single child with atypical (non-syndromic) autism. The cells were obtained via a novel program that Dr. Muotri and colleagues started, called “the Tooth Fairy Project.” The discarded baby tooth of a child with ASD was mailed to the research team at UCSD. The team is able to obtain pulp cells from such teeth, which can be reprogrammed to behave like stem cells. These “induced pluripotent stem cells” are then tweaked to develop as neurons, like those found in the brain. (Brain cells can’t be sampled from living humans.)

Using this method, the researchers were able to closely observe how the nerve cells developed, looking in particular for the way mutated genes potentially involved in causing the child’s illness altered the cells’ biology. In recent years, a number of genetic mutations were found to be associated with ASD. But only recently has the scientific community begun to focus on what functions these genes perform and how mutations may prevent them from performing those functions––and possibly contributing to ASD pathology.

Genetic sequencing revealed that the ASD patient whose cells were sampled in this study had a mutation in a gene called TRPC6, which affected one of the gene’s two copies. (Other studies have linked this gene with Rett syndrome, an autism spectrum disorder.) The team also noticed that activity of the TRPC6 gene was affected by levels of a protein called MeCP2. Mutations in the gene that encodes this protein are a known cause of Rett syndrome. The affected child does not have Rett, suggesting that different ASDs with different symptoms may strike some of the same gene pathways. One major hope of researchers in autism and other complex genetic illnesses, including schizophrenia, is that while patients may show a wide range of symptom combinations, these might stem from defects in a comparatively small number of convergent gene pathways. The findings of this study are consistent with that hypothesis.

Dr. Muotri and colleagues engineered mice with the equivalent of the TRPC6 mutation found in the child. They observed various pathologies in these mice, affecting neural development, shape, and function. Remarkably, by giving the mice a drug called hyperforin, they were able to reverse or mute the impact of the TRPC6 mutation. This drug is known to spur expression of the protein encoded by the TRPC6 gene. Although this finding is only suggestive––the impact of drugs in mice cannot be simply extrapolated to humans––it does suggest that in certain kinds of ASD and perhaps similar illnesses in which this particular gene mutation causes pathology, drug treatments could help alleviate symptoms.

The “Tooth Fairy” research team also included:  

• Hongjun Song, Ph.D., 2008 NARSAD Independent Investigator Grantee, Johns Hopkins University
• Guo-il Ming, M.D., Ph.D., 2010 NARSAD Independent Investigator Grantee, Johns Hopkins University
• Matthew W. State, M.D., 2012 Foundation Ruane Prizewinner for Outstanding Achievement in Child and Adolescent Psychiatric Research, University of California, San Francisco

Read the abstract of this research paper.

Read more about this research.