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Fast-fail for success
LOS ANGELES—Can autism actually be cured? James McCracken, a professor of psychiatry at the University of California, Los Angeles (UCLA), thinks so. Apparently, so does the National Institute of Mental Health (NIMH), which in April awarded a $9-million contract to UCLA for an ambitious plan to fast-track a study of promising new drugs that may help restore normal development and brain function in children with autism spectrum disorders (ASD).
Led by McCracken, the project's principal investigator and director of the division of child and adolescent psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA, the effort will create and lead a network of U.S. academic centers to carry out early high-risk/high-reward studies of experimental medications over a three-year period. The goal of the project, titled New Experimental Medicine Studies: Fast–Fail Trials in Autism Spectrum Disorders, is to determine within weeks—rather than years—if a particular pharmacological compound is working or not.
The NIMH initiative, launched in February, attempts to redefine clinical trials for autism by funding short, biomarker-based studies to allow investigators to quickly rule out ineffective compounds. To do this, researchers will focus on analyzing how novel molecular and clinical targets for ASD are affected by both new and repurposed compounds. The outcome is expected to lead to an enhanced understanding of the mechanisms that underlay ASD and the development of innovative pharmacological treatment approaches for the disorder.
At UCLA, testing will involve scientists and clinicians from the fields of psychiatry, radiology and biostatistics, while the UCLA Clinical and Translational Science Institute will use sophisticated measures of brain and behavioral responses to identify signs of successful drug action in key brain regions. Positive findings could then be followed up by other large-scale national and international studies.
There is an urgency to this experiment, as the Centers for Disease Control and Prevention estimates that one in 88 children in the United States has been identified with an ASD. Despite the difficulties in treating the pervasive development disorder, which is characterized by delays in basic communication, socialization and daily life skills that impact every aspect of a child's life and into adulthood, McCracken declares, "This is definitely the most exciting time yet to be involved in treatment research for ASD."
"Our basic science colleagues are generating enormous information on the likely underlying causes of this common and often disabling condition," he says. "We are well positioned to apply the basic science and find drugs that make a difference."
Although behavioral and developmental interventions, including programs developed at UCLA in the 1980s, offer hope of improvement for many, and behavioral and medical interventions can address behavior problems, at present, there are no established medical treatments for the core social deficits of ASD, despite its acknowledged genetic and biological basis.
Ironically, the explosion of basic-science knowledge about ASD and possible drug treatments is emerging at a time when major pharmaceutical companies are canceling drug-development programs for ASD and other mental disorders, citing costs, difficulties and the recent failures of what were deemed good prospects, according to the NIMH. Many U.S. National Institutes of Health officials, research scientists and affected families are fearful that progress in medication development will slow in the face of the industry's retreat from neuroscience drug development.
"It's a challenge," McCracken concedes. "There are now so many possible experimental medicines and approaches from basic science for ASD that we find ourselves way behind. We need a new paradigm to test the many possible compounds, and we need to quickly and accurately identify which ones are really ready for 'prime time.'"
Large-scale studies of possible medications take years and can cost upwards of $500 million dollars before yielding an approved, marketed drug, McCracken points out.
Recent progress in identifying the genes and biological components involved in autism spectrum disorders (ASD) holds great promise for the identification of life-changing treatments for individuals of all ages, McCracken says.
"Current medical treatments are commonly prescribed by physicians for ASD, but only to manage difficult behaviors like aggressiveness, hyperactivity and self-injury," he says. "Such treatments can be important and helpful, but they do not impact the core problems of the disorders."