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Rett Syndrome Research News

Scientists at the Toronto Western Research Institute at the University Health Network have revealed restored function in the Rett syndrome mouse model across a broad range of symptoms. The study was led by Dr. James H. Eubanks, PhD and recently published in Human Molecular Genetics (Pubmed abstract).


Rett syndrome is a severe neurological condition that affects mostly females.  The Methyl-CpG-binding protein 2 (MeCP2) gene studied by the Eubanks group may also be implicated in other X-linked genetic conditions, such as Angelman syndrome.  Rett syndrome presents in similar ways to Autism and to movement disorders such as Parkinson’s disease.  Therefore, scientists look at these kinds of discoveries with great interest.


Previous studies have shown that symptoms of Rett syndrome may be reversible.  In 2007, Dr. Adrian Bird, PhD discovered that delayed MeCP2 reactivation in the mouse model resulted in improvement in many Rett-like symptoms.  Dr. Eubanks explains, “This was a monumental study, but it did not test whether or not specific behaviors with direct relevance to those seen in Rett syndrome, or alterations in brain wave activity patterns, would be improved.  We wanted to use a battery of tests to see if the rescue would apply across the board to different regions of the brain, and improve the circuitries responsible for these different behaviors.”


In Eubanks’ study, detailed investigations compared both male and female “rescued” mice to those with MeCP2 deficiency.  Following MeCP2 reactivation, significant improvements were seen in motor and anxiety-like behaviour, seizure activity, and regulation of body temperature.  In addition to specific behavior improvements, Eubanks says, “the strength of specific brain wave patterns are brought back to normal following reactivation.”  And the lifespan of the female rescue mice was improved to a level comparable to wild-type (normal) mice.


The significant differences in male and female mouse models of this X-linked disorder add to the complexities of Rett syndrome research.  Most scientific studies to date have focused on male mouse models.  Eubanks has extensively studied female MeCP2-deficient mice – always comparing them to the male model and wild type – because it is the gender-appropriate model for the clinical disorder.  According to Eubanks, “for most of the behavioral tests and EEG analysis we did, the females recovered to levels even better than that of the male rescue mice.”


The results from this investigation provide enormous hope for people with Rett syndrome and related conditions.  Eubanks explains, “Our work shows in the gender appropriate model of Rett syndrome, a very delayed reactivation of MeCP2 in really sick mice reverses not only their general malaise, but improves – in some cases all the way to normal levels – deficits in specific behaviors directly relevant to Rett syndrome.  The improvement involved all of the neural circuits we examined.  In the range associated with cognition and thought processing, we saw almost a complete recovery in power in the female rescue mice.  So the rescue we saw really does indicate the MeCP2-deficient brain is not damaged beyond repair.  It seems to be impaired in a way that does not prevent it from reaching a full recovery.”


Still, this study involves the mouse model for Rett syndrome.  There is work to be done to see similar results in humans.  You can’t do to humans what was done to these mice.  Studies such as this one provide further specific evidence of what might be possible in human patients.  Researchers will continue to generate ideas for treating patients when they see this remarkable potential for recovery.  For Eubanks, these results have encouraged him to pursue gene therapy for patients with Rett syndrome.  “This study shows it is possible, and we now need to develop a gene therapy system that will allow MeCP2 to be delivered in a way similar to what was done in the current study.  Our lab is currently testing a new system we think may get us closer to this goal.”


Dr. Eubanks is a member of the Ontario Rett Syndrome Association’s Research Advisory Committee. He is also O.R.S.A.’s 2012 Award of Merit recipient for demonstrating outstanding commitment to the mission of the association.  He has shown true dedication in making a difference in the lives of those living with Rett syndrome.




Rescue of behavioral and EEG deficits in male and female Mecp2-deficient mice by delayed Mecp2 gene reactivation. Lang M, Wither RG, Colic S, Wu C, Monnier PP, Bardakjian BL, Zhang L, Eubanks JH. Human Molecular Genetics. 2013 September 17.





This work was supported by the operating grants from the Canadian Institutes of Health Research to J.H.E. (MOP-106481) and B.L.B. (MOP-286154), and a proof of concept grant from the Ontario Rett Syndrome Association. M.L. was the recipient of a University of Toronto Entry Fellowship, and S.C. was the recipient of Queen Elizabeth II Graduate Scholarship in Science and Technology. Funding to pay the Open Access publication charges for this article was provided by Canadian Institutes of Health Research Grant MOP-106481.



James Eubanks


Toronto Western Research Institute

399 Bathurst Street

Toronto, Ontario, M5T 2S8

Telephone: 416-603-5800, ext. 2933

Telefax: 416-603-5745

Email: jeubanks@uhnres.utoronto.ca