Researchers have used a new genetic tool to identify the underlying cause of a rare form of autism spectrum disorder (ASD) complicated by epilepsy. They then tailored a simple treatment – an amino acid supplement – to address the defect. It reduced autism symptoms and seizures in mice with the same genetic mutation. The report appears in this week’s online issue of Science.
"Genetic studies are helping us identify subgroups of individuals with ASD who may respond to specific treatments," says Autism Speaks Chief Science Officer Geri Dawson, Ph.D. "This study provides promising results of a new treatment approach for a rare form of autism that now must be tested in people with this form of ASD."
Scientists at the University of California, San Diego and Yale led the international research team. They used the emerging technology of exome sequencing to study two families that suffered from this rare form of autism. They identified a gene mutation that speeds up the metabolism of certain amino acids that must come from food. As a result, affected individuals suffer deficiencies in these “branch chain amino acids.”
"It was very surprising to find mutations in a potentially treatable metabolic pathway specific for autism," says senior author Joseph Gleeson, M.D., of UCSD. "What was most exciting was that the potential treatment is obvious and simple: Just give affected patients the naturally occurring amino acids their bodies lack."
To test this possibility, the researchers studied a line of mice engineered with a mutation in the same gene. Treating the mice with high doses of the amino acids improved their epileptic and autism-like symptoms.
"Studying the animals was key to our discovery," says first author Gaia Novarino, Ph.D., also at UCSD. "We found that the mice displayed a condition very similar to our patients. [They] also had spontaneous epileptic seizures just like our patients. Once we found that we could treat the condition in mice, the pressing question was whether we could effectively treat our patients."
The scientists gave the amino acid supplement to members of the two families in whom they had identified the mutation. The supplements normalized levels of the branch chain amino acids in the family members blood samples. The next step, the researchers say, is to determine whether this correction can reduce autism symptoms and epileptic seizures.
"We think this work will establish a basis for future screening of all patients with autism and/or epilepsy for this or related genetic mutations, which could be an early predictor of the disease," the researchers conclude. "What we don't know is how many patients with autism and/or epilepsy have mutations in this gene and could benefit from treatment, but we think it is an extremely rare condition." Roughly one-quarter of patients with autism also suffer from epilepsy, a brain disorder characterized by repeated seizures or convulsions over time.
“This is a prime example of a translational research approach that converts cutting-edge scientific findings into potential treatments,” says Daniel Smith, Ph.D., Autism Speaks senior director of discovery neuroscience. “It also offers a glimpse into a future of personalized medicine in autism. The causes and symptoms of autism vary widely, and treatment success may depend on biologically matching individuals and treatments. If BCAA supplementation improves outcomes in the families involved in the study, then understanding how BCAAs affect the brain will reveal its potential for wider use.”
Autism Speaks continues to fund a wealth of cutting-edge research into the genetics and treatment/prevention of autism and related medical conditions such as epilepsy. You can explore these and other studies using our Grant Search.