Autism cure by gene therapy

shank3 - Copy

Nothing short of an autism cure is promised by this hot new research paper.

Among many thousands of proteins that a neuron needs to make in order to function properly there is one called SHANK3 made from the gene shank3. (Note the customary writing: by consensus, a gene’s name is written using small caps and italicized, whereas the protein’s name that results from that gene expression is written with caps).

This protein is important for the correct assembly of synapses and previous work has shown that if you delete its gene in mice they show autistic-like behavior. Similarly, some people with autism, but by far not all, have a deletion on Chromosome 22, where the protein’s gene is located.

The straightforward approach would be to restore the protein production into the adult autistic mouse and see what happens. Well, one problem with that is keeping the concentration of the protein at the optimum level, because if the mouse makes too much of it, then the mouse develops ADHD and bipolar.

So the researchers developed a really neat genetic model in which they managed to turn on and off the shank3 gene at will by giving the mouse a drug called tamoxifen (don’t take this drug for autism! Beside the fact that is not going to work because you’re not a genetically engineered mouse with a Cre-dependent genetic switch on your shank3, it is also very toxic and used only in some form of cancers when is believed that the benefits outweigh the horrible side effects).

In young adult mice, the turning on of the gene resulted in normalization of synapses in the striatum, a brain region heavily involved in autistic behaviors. The synapses were comparable to normal synapses in some aspects (from the looks, i.e. postsynaptic density scaffolding, to the works, i.e. electrophysiological properties) and even more so in others (more dendritic spines than normal, meaning more synapses, presumably). This molecular repair has been mirrored by some behavioral rescue: although these mice still had more anxiety and more coordination problems than the control mice, their social aversion and repetitive behaviors disappeared. And the really really cool part of all this is that this reversal of autistic behaviors was done in ADULT mice.

Now, when the researchers turned the gene on in 20 days old mice (which is, roughly, the equivalent of the entering the toddling stage in humans), all four behaviors were rescued: social aversion, repetitive, coordination, and anxiety. Which tells us two things: first, the younger you intervene, the more improvements you get and, second and equally important, in adult, while some circuits seem to be irreversibly developed in a certain way, some other neural pathways are still plastic enough as to be amenable to change.

Awesome, awesome, awesome. Even if only a very small portion of people with autism have this genetic problem (about 1%), even if autism spectrum disorders encompass such a variety of behavioral abnormalities, this research may spark hope for a whole range of targeted gene therapies.

Reference: Mei Y, Monteiro P, Zhou Y, Kim JA, Gao X, Fu Z, Feng G. (Epub 17 Feb 2016). Adult restoration of Shank3 expression rescues selective autistic-like phenotypes. Nature. doi: 10.1038/nature16971. Article | MIT press release

By Neuronicus, 19 February 2016


4 thoughts on “Autism cure by gene therapy

  1. Dear Sir

    Myself Vijesh kaimal from Cochin India, I am the father of 5 year old boy, He has PHPV (Persistent Hyper plastic Primary Vitreous) in both eyes, we identified from his 45th day. We went all main hospitals in south India, They are helpless. And also he is having some autistic behaviours like developmental delays and He can’t speak up to the mark his response to our speech is less and also some hyper activities. Now we are started some therapies.
    Sir I have a doubt for his case is this autistic behavior leads to his eye problem or his eye problem leads to autistic behavior.
    If any treatment in gene therapy to solve his autistic behaviour may can change his eye problems.

    Thanking you

    Vijesh kaimal



    1. Dear Mr. Kaimal,

      I am sorry to hear about your son’s problems. I also have no idea if the vision problems are connected to the behavioral problems. The gene shank3 that was the focus of this paper is present only in a very small portion (1% to be exact) of the people diagnosed with autistic spectrum disorders. Moreover, this is a proof-of-principle paper, meaning there would be years until this gene therapy will be approved, provided it works in the first place on humans. The paper offers hope for a cure for that 1%, but not a cure, yet. For now, I would advise you to continue the therapies; most of them have been proven to help with behavioral problems.

      Kind Regards,


  2. Hi. I have a son with a shank3 gene mutation at exon 11, my son has autism between moderate and severe on the autism spectrum and intellectual disability. I have friends in the 22q13 syndrome whos has children with deletion of one copy of shank3 gene being knocked out with children with ID and autism. what would be the difference between turning back on a copy of shank3 gene for a knock out gene and a mutated gene at a certain exon, shank3 gene is a big gene. the situation with mutated genes is that amino acids will change depending on the mutation and the location of the mutation at exon levels, but a totally knocked out gene is not a protein producer at all. You also have the problem with shank3 gene micro deletion. thank you.


  3. Hi. I’m really sorry about your son’s problems. Having read your comment/question several times, I’m not sure I understand it. Is a question about the difference between total and partial gene restoration? Or the difference between having no shank3 or a bad shank3? Seems like you did your homework and know a lot about this protein, which means you also know that it is a hub or scaffold protein, coordinating many different signalling pathways, some of which I suspect are unknown as of yet. As you said, no gene means no protein, but a mutated gene could mean a lot of things: produces protein that is useless, retains some function before degradation or is even destructive, or doesn’t even get to the protein stage but it produces regulatory RNAs. I really couldn’t tell you what would be the cellular consequence of the E11 mutation, since it’s not really my field, but perhaps the corresponding author of the article could, Dr. Guoping Feng. You can write to him here: Thanks for reading!


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