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Translational Research Places the Spotlight on

Treatment of Neurodevelopmental Disorders
September 21, 2009

Translational research takes knowledge learned from basic biology discoveries and applies it to the development of treatment strategies. Using mice that have been altered to carry a genetic mutation, several studies published in 2008 showed that an FDA-approved drug, Rapamycin, can reverse the hallmark signs of a rare human genetic disorder called Tuberous Sclerosis Complex (TSC). These studies generated additional insight into the near-term possibility of drug treatments for neurodevelopmental disorders related to autism.

Published on the heels of similar translational research reported last year for Fragile X, Rett and Angelman syndromes (see 2007 Potential Reversal of Neurodevelopmental Disorders), the TSC findings provide yet another example of what appears to be a surprising ability to intervene in cases of abnormal brain development. The new studies, some of which were funded in part by Autism Speaks, utilized model systems to genetically-mimic TSC in mice and test whether the damage to the nervous system could be repaired after the animals had become adults. Researchers at Harvard Medical School harvested brain cells from the mice to grow in culture and found that administration of Rapamycin, which targets the biochemical pathway disrupted in TSC, could reverse the abnormal cell shape. Separate teams of researchers from UCLA, Harvard, and Washington University went one step further by demonstrating that injecting the same drug into the mice themselves rescues the neurological impairments in the animals that carry copies of the defective TSC genes. Together, these studies continue to promote the theme of the unexpected reversibility of neurodevelopmental disorders.

Clinical trials of Rapamycin for individuals with TSC are currently on-going (see Arrival of Clinical Trials for Neurodevelopmental Disorders). Because more than half of the TSC affected individuals also have Autism Spectrum Disorders, these stunning results give additional hope that autism eventually may be treatable by novel drug therapies. Besides the therapeutic implications, the studies served to document the importance of model systems and the power of translational research in greatly speeding the design of innovative therapeutics.


Choi YJ, et al. Tuberous sclerosis complex proteins control axon formation. Genes Dev. 2008 Sep 15;22(18):2485-95.

Ehninger D, et al. Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis. Nat Med. 2008 Aug;14(8):843-8. Epub 2008 Jun 22.

Meikle L, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008 May 21;28(21):5422-32.

Zeng LH, et al. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol. 2008 Apr;63(4):444-53.