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 in 2007 for Fragile X, Rett and Angelman syndromes, 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. 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.
Did you know?: This completely unexpected ability to treat neurodevelopmental disorders has re-focused the field on the importance of appropriate autism animal models for testing of therapeutic approaches. To facilitate proper evaluation of animal models of autism, in 2008 Autism Speaks organized a Mouse Behavior Workshop that brought in experts to determine future needs and group recommendations towards facilitating animal models for autism. Later the same year, Autism Speaks sponsored a symposium at the annual Neurotoxicology meeting to encourage new thinking about how autism model systems may be used to study environmental toxicants and their interaction with genetic susceptibility.
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 11th item, Translational Research Takes Hold , is from Autism Speaks’ Top 10 Autism Research Events of 2008.
