November 27, 2014

expert reaction to reversing common form of autism in mice

A study published in the journal Cell Reports has suggested that increased levels of a specific protein can lead to outcomes which are similar to those seen in fragile X syndrome (FXS). FXS is a genetic cause of autism, and the paper reports that the levels of the protein in question can be controlled by modification of a second protein.

Prof Jeremy Turk, Consultant Child & Adolescent Psychiatrist, Southwark Child & Adolescent Mental Health Neurodevelopmental Service, South London and Maudsley NHS Foundation Trust, and Professor of Developmental Psychiatry, King’s College London’s Institute of Psychiatry, Psychology and Neuroscience (IoPPN), said:

“This is an impressive, detailed and comprehensive account of a number of scientific experiments and investigations into the underlying molecular biological basis of brain structure and behaviour anomalies in fragile X syndrome. The research is of high quality and illustrates, through use of mouse models, the potential for medication interventions to ameliorate, and even reverse, the adverse developmental consequences of having a specific genetic condition – in this instance fragile X syndrome.

“Fragile X syndrome is the most common identifiable inherited cause of intellectual (learning disability) and autism spectrum disorders.  It affects intellectual ability, speech and language development, social functioning and attentional skills, resulting in lifelong dependency needs.  Currently there are a range of biological, psychological, educational and social interventions and supports available, but these tackle the consequences of having fragile X syndrome rather than the underlying cause and hence can only bring relative symptomatic relief.

“There has already been considerable research on the molecular basis of fragile X syndrome as well as a number of other single gene disorders including tuberous sclerosis, neurofibromatosis and Down’s syndrome.  However, this report of detailed research suggests a novel medical approach based on increased understanding of the underlying neurological and biochemical anomalies in fragile X syndrome and how they may be addressed.  The research is particularly impressive because of the detail and range of studies undertaken.

“However, caution is needed because earlier similar studies of possible medication, where initial animal research was promising, did not yield positive findings when the medication was studied in humans. Nonetheless, it provides hope not only for those with fragile X syndrome, but also for individuals with a range of other genetically determined conditions causing complex and multiple developmental disabilities. It may be possible in the future to provide medical treatments for conditions which up till now have been considered to be incurable. The impact of such treatments would be enormous but considerable further research is noted to confirm the findings and to explore whether the benefits witnessed in mice will translate to positive improvements in humans.

“Given the strong genetic basis to autism spectrum disorders, the possible importance of the research extends well beyond the specific area of fragile X syndrome understanding and treatment. Families who have members with these conditions will be justified in being excited by these discoveries, but will need to be aware of just how long it is likely to take to develop safe and effective treatments for humans. In the meantime they should continue to access already established biological, psychological, educational and social treatments and supports.”

‘Pharmacogenetic Inhibition of eIF4E-Dependent Mmp9 mRNA Translation Reverses Fragile X Syndrome-like Phenotypes’ by Gkogkas et al. published in Cell Reports on Thursday 27^th November.

Declared interests

Jeremy Turk: “I have longstanding clinical and academic interests in fragile X syndrome, having undertaken my research doctoral thesis on it.  I continue to research, teach and clinically practice in meeting the mental health needs of individuals with a range of developmental disabilities including those with fragile X syndrome.  I am professional advisor to the UK Fragile X Society and am on the scientific and clinical professional advisory committee of the US International Fragile X Federation.”