Contribution of mGluR5 to pathophysiology in a mouse model of human chromosome 16p11.2 microdeletion

Original research article by Di Tian et al. (2015).

Read the abstract here.

The 16p11.2 deletion is thought to be the most common of the many genetic causes of autism, accounting for up to 1% of all cases of autism. Fragile X syndrome is the second most common genetic cause of autism, and it involves a different chromosome, the X chromosome. These different genetic causes of autism affect similar biological processes in the brain, and these effects can result in autism.

The researchers in this study used mice with a genetic change (in this case, a mouse model of the 16p11.2 deletion) to study the learning, behavioral, and intellectual features of the 16p11.2 deletion. Scientists can also use mouse studies to learn about potential treatments for a condition.

No medications are available to treat symptoms of autism. Within the past several years, though, many researchers, including Mark Bear (an author of this article) and his research team, have worked toward developing a medication to treat symptoms of fragile X syndrome. They began with mouse models and eventually worked toward studying the use of this new medication in people who have the syndrome. While the preliminary results were not perfect, they were promising, so in late 2013 the FDA approved a second phase of drug trials for fragile X syndrome.

Does this mean we will be able to treat the symptoms of autism? In some children with a 16p11.2 deletion or with fragile X, it might be possible. The reason is that the 16p11.2 deletion and fragile X both lead to problems with a protein, mGluR5, that is important for managing messages related to memory and learning. Because the two conditions involve problems with the same protein, there’s a possibility for a shared treatment with a drug that targets this protein, called an mGluR5 antagonist.

Can 16p11.2 families expect to see the same results as fragile X families? Not necessarily, but at least we have a place to start. While the 16p11.2 deletion and fragile X do both involve problems with mGluR5, they are different problems. In people with fragile X syndrome, the mGluR5 problem causes too much messaging, while in 16p11.2 deletion, the problem is too few messages.

Randi Hagerman, director of the MIND Institute at UC Davis, says, “I think that the mGluR5 antagonists are going to be helpful for young children with fragile X, but I think they could also be helpful for many young children with autism, particularly this 16p11.2 microdeletion subgroup.”

It will take many years before drugs have worked their way through the FDA approval process, but this is definitely an exciting time.

Want some other perspectives? See these commentaries:

SFARI: Drug abates symptoms in two genetic models of autism.

MIT News: New findings reveal genetic brain disorders converge at the synapse.