VIP Summary #4: Research on possible treatments for 16p11.2 - enhancing the need to study the community

Article summary and SVIP commentary:

Here at Simons VIP Connect, we were really excited about the information presented in a recent study titled, "Contribution of mGluR5 to pathophysiology in a mouse model of human chromosome 16p11.2 microdeletion." We've been hearing about this molecule in relation to autism treatment for the past 5-10 years, but have only heard about it in relation to a handful of genetic causes of autism. Now we're hearing about it in relation to 16p11.2, and it's really exciting. Below, Andy Faucett, one of the founders of Simons VIP Connect comments on the necessity for families to participate in this community and research study to further our understanding of the deletion.


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

Original article by: Dr. Di Tian et al.

Read the abstract here:

Before we can get into some of the exciting details from this article, we need to start off with some background information. As you may already know, there are hundreds of genetic causes of autism. The 16p11.2 deletion is thought to be the most common genetic cause of autism, accounting for up to 1% of all cases of autism. Fragile X syndrome is the second most common genetic cause of autism that involves an entirely different chromosome (the “X” chromosome). You might start hearing more about Fragile X syndrome in relation to 16p11.2 deletion syndrome, which is why we wanted to give you some background information about how common they are, and how these two different genetic causes of autism actually affect similar biological processes in the brain that result in autism.

As a heads-up, this research article, titled “Contribution of mGluR5 to pathophysiology in a mouse model of human chromosome 16p11.2 microdeletion”, is very technical. The researchers of this study used mice with a genetic change (in this case, a mouse version of the 16p11.2 deletion) to study the specific learning, behavioral, and intellectual features of this condition. Using mouse studies, scientists can also learn about potential treatments for a condition. Even though the scientific details of this research study can be overwhelming to read, we have some take-home points that our Simons VIP families may find interesting.

Until very recently, there weren’t specific medications available to treat autism. Within the past several years, many researchers, including Mark Bear (an author of this article) and his research team, have worked toward understanding the biology of Fragile X syndrome with the goal of creating a medication to treat symptoms of this syndrome. They began with mouse models and eventually worked toward studying the use of this new medication in people who have Fragile X syndrome.  While the preliminary results were not perfect, they were promising, so the FDA approved a second phase of drug trials for Fragile X syndrome in late 2013.

Does this mean we can treat the symptoms of autism? In some kids with 16p11.2 deletion or with Fragile X, it might be possible. The reason for this is because 16p11.2 deletion and Fragile X both lead to problems with the same protein in the body that is important for managing messages related to memory and learning; this protein is called mGluR5. Because of this shared messaging problem, there’s a possibility for a shared treatment that targets this protein, a type of drug called an mGluR5 antagonist.

Does this mean we can expect the same results for our 16p11.2 families? Not necessarily, but it does mean that we have a place to start. One major difference that will have to be considered is that while 16p11.2 deletion and Fragile X do both involve problems for mGluR5, they are different problems.  In people with Fragile X syndrome, the mGluR5 problem causes too much messaging, while in 16p11.2 deletion, too few messages are made.

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. Cheers to the future!

 Want some other perspectives? Check out these commentaries:

  1. SFARI:
  2. MIT News:

Go Home