UCLA researchers will create and lead a network of U.S. academic centers that will carry out early "high risk/high reward" studies of experimental medications over a three-year period. The goal of the project, New Experimental Medicine Studies: Fast-Fail Trials in Autism Spectrum Disorders, is to determine within weeks rather than years ("fast") if a particular pharmacological compound is working or not ("fail").
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, said the project's principal investigator, Dr. James McCracken, a professor of psychiatry and director of the division of child and adolescent psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.
"Current medical treatments are commonly prescribed by physicians for ASD but only to manage difficult behaviors, like aggressiveness, hyperactivity and self-injury," McCracken said. "Such treatments can be important and helpful, but they do not impact the core problems of the disorders.
"This is definitely the most exciting time yet to be involved in treatment research for ASD," he added. "Our basic science colleagues are generating enormous information on the likely underlying causes of this common and often disabling condition. We are well positioned to apply the basic science and find drugs that make a difference."
ASD is increasingly recognized by clinicians. The Centers for Disease Control and Prevention estimates that one in 88 children in the United States has been identified with ASD, which is characterized by delays in the development of effective communication and social relationships and which impacts nearly every area of child and adult functioning.
Behavioral and developmental interventions, including programs developed at UCLA in the 1980s, offer significant hope of improvement for many, and behavioral and medical interventions can be helpful with behavior problems. But at present, there are no established medical treatments for the core social deficits of ASD, despite its acknowledged genetic and biological basis.
"It's a challenge," McCracken said. "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.'"
Currently, McCracken noted, large-scale studies of possible medications take years and can cost upwards of $500 million dollars before yielding an approved, marketed drug. The three-year NIMH contract will support a new approach involving multiple "fast-fail" studies, which could accelerate progress by providing an early "yes or no" assessment of various compounds.
The initiative 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. 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.
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. Many 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.
Funding from the NIMH comes under contract No. HHSN-271-2012-00005-I. In addition to McCracken, UCLA collaborators will include Susan Bookheimer, Sandra Loo, Joseph O'Neill and Edythe London from the department of psychiatry; Dr. Albert Thomas from the department of radiological sciences; and Catherine Sugar from the department of biostatistics. Additional colleagues from other institutions around the country are expected to participate in the new network.