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Calls to Action

Arrival of Clinical Trials

for Neurodevelopmental Disorders
September 21, 2009

The hope of therapeutics to target the core biological impairments in autism would not have seemed realistic even five years ago. The year 2008 saw the first public announcement of early promising results in clinical trials designed for disorders with significant autism overlap, and several new clinical trials of biological pharmaceuticals are now in various stages of development.

Approximately one third of individuals with Fragile X Syndrome, the most common form of inherited mental retardation, also are diagnosed with autism, and almost all have features similar to autism, such as social anxiety, abnormal language, and atypical behaviors. Similarly, about half of the individuals with Tuberous Sclerosis Complex (TSC), a disorder characterized by brain tumors and seizures, also have an Autism Spectrum Disorder (ASD). Exciting translational research published last year using animal models of Fragile X and Rett

syndromes (see 2007 Potential Reversal of Neurodevelopmental Disorders) and this year using models of TSC (see Translational Research Places the Spotlight on Treatment of Neurodevelopmental Disorders) has provoked a dramatic conceptual shift: whereas before it was believed disorders that impact the brain early on are not treatable unless intervened with immediately, they are now seen as potentially correctable, even later in life. Moving this concept into the clinic is the next step.

In 2008 researchers from the MIND Institute and Rush University reported results from the first trial of a class of compounds known as mGluR5 antagonists, drugs designed to inhibit a very specific subtype of glutamate signaling in the brain that researchers believe is overactive in individuals with Fragile X. Results from the small trial indicate that six out of the twelve adults with Fragile X showed improvements in cognitive deficits. In June 2008, Novartis Pharmaceuticals began enrollment of a clinical trial in Europe to test mGluR5 antagonists in adults with Fragile X. Also in 2008, Seaside Therapeutics, a small biotechnology company in Boston, began enrollment for a clinical trial based on a different biological approach to treating Fragile X, utilizing compounds known as GABA-B agonists to modulate glutamate signaling. Seaside Therapeutics has announced plans to expand this trial to patients with autism later this year, and is also aiming to launch a clinical trial of its own formulation of a specific mGluR5 antagonist for Fragile X. (Read more about this study, including information on participation, here)

Finally, although still ongoing, in 2008 UK researchers running a multi-site, multi-year clinical trial of the drug Rapamycin in individuals with TSC reported positive outcomes on short-term memory tests of those receiving treatment. Rapamycin, already FDA-approved for cancer, targets the brain signaling pathway that has been found to be disrupted in TSC and that has recently been implicated in autism as well (see 2007 Converging Signaling Pathways).

The ideas for these clinical trials derived entirely from research designed to uncover the basic biochemical mechanisms that cause the disorders. Genetic breakthroughs in Tuberous Sclerosis Complex and Fragile X led directly to discovery of the physiological pathways disrupted by the genes, which immediately

inaugurated the search for compounds to overcome those disruptions, first in model systems and now in humans. It is equally noteworthy that none of these trials would be moving forward without the support and funding of the advocacy organizations Tuberous Sclerosis Alliance, Tuberous Sclerosis Association, and FRAXA Research Foundation, illuminating the incredible power of community advocacy organizations in bringing partners together to make sure important discoveries are made!


Berry-Kravis EM, et al. A pilot open-label single-dose trial of fenobam in adults with fragile X syndrome. J Med Genet. 2009 Jan 6. [Epub ahead of print]