|Gimme five... @ Wikipedia|
Enter then yet another 'we can reverse them' mouse study by Christos Gkogkas and colleagues* (a splendid Greek surname reflective of the heavy pronunciation of 'G', as in Gogas) published in the premier journal Nature.
An accompanying news piece also published in Nature by Dan Jones** delivers the headline: "Autism symptoms reversed in mice" and quite a nice summary of the research results. In light of this I'm not going to do a clinical dissection of the Gkogkas study, but rather summarise hopefully without plagiarising. Note also to Dan Jones, the current CDC estimates for autism is 1 in 88 not 1 in 110. Sorry to be pedantic.
So assuming I understand correctly, take a mouse - a specially bred mouse - which lacks a certain gene, Eif4ebp2, which codes for a certain protein (4E-BP2), which moderates the translation of certain mRNA, which potentially impacts on the production of neuroligins (NLGNs) as in increases production of them, which in turn effects synapses. The end result according to the Gkogkas study is synaptic hyperconnectivity and autistic-like symptoms. Don't quote me on this by the way.
More than that however was the suggestion that such symptoms might be reversed by the the use of 'an experimental cancer drug' which works by reducing protein synthesis. Said drug which I can't actually name yet, seemed to do the trick and positively affected certain social-based symptoms. "The team extended these findings by directly suppressing the translation of NLGN proteins using short interfering RNAs [via a non-replicating virus vehicle]" according to Jones, and hey presto, similar effects.
Neuroligins are synaptic cell-adhesion molecules which together with neurexins form a complex which are involved in synapse development and maturity. The term 'shake hands' tends to be used quite a bit when talking about these molecules; quite a good overview being this one from Thomas Südhof*** (open-access). Gkogkas reports that one specific neuroligin seems to be a primary target of their research: neuroligin 1. Other research on neuroligins and autism tends not to be so specific, bearing in mind that this is still a growth area of investigation.
As with the other autism-mouse research these are interesting results. The synaptic focus of this work will probably find quite a lot of support from quite a large contingent of the autism research community given the focus on (a) the brain and (b) the excitatory-inhibitory balance in brain cells; said balance already having surfaced in other autism research (see here).
Translating such research into benefiting real people with autism is the next step but likely however not to be a quick next step given that the experimental drug used to reduce protein synthesis was toxic (thanks Jon Brock!) and the requirement for looking at real people with autism (sorry, autisms) and all the other comorbidities which are more than likely to be present. As far as I am aware issues with 4E-BP2 in autism for example is still more of an idea than an actuality aside from papers like this one from De Rubeis & Bagni**** (open-access) looking again at autism-like behaviours in relation to FXS. The Gkogkas study at least offers a few more directions for autism research to take and demonstrating once again the invaluable contribution of animal models to autism research.
* Gkogkas CG. et al. Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature. November 2012.
** Jones D. Autism symptoms reversed in mice. Nature. November 2012.
*** Südhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature. 2008; 455: 903-911.
**** De Rubeis S. & Bagni C. Regulation of molecular pathways in the Fragile X Syndrome: insights into Autism Spectrum Disorders. J Neurodev Disord. 2011; 3: 257-269.
Gkogkas, C., Khoutorsky, A., Ran, I., Rampakakis, E., Nevarko, T., Weatherill, D., Vasuta, C., Yee, S., Truitt, M., Dallaire, P., Major, F., Lasko, P., Ruggero, D., Nader, K., Lacaille, J., & Sonenberg, N. (2012). Autism-related deficits via dysregulated eIF4E-dependent translational control Nature DOI: 10.1038/nature11628