This guest post is by Nancy Jones. Nancy Jones, Ph.D. is the Program Director of the Autism Treatment Network and Autism Clinical Trials Networks at Autism Speaks. Nancy received her Ph.D. in Applied Linguistics from the University of California, Los Angeles where she focused on brain and language development in children with developmental disorders.
Finding appropriate treatments for autism is a challenge for families and clinicians alike. While behavioral treatments are an effective mainstay of therapeutic approaches, many individuals with autism benefit from the addition of medicinal interventions, particularly for problem behaviors, severe self-injury, and disruptive repetitive behaviors. A major impediment to finding effective treatment regimens is the fact that individual responses to the same medicine can vary greatly due to genetic background. Finding the most effective dose with the fewest side effects means slowly trying various doses, and possibly having to switch medicines. This is not only a challenge for the physician, but is also a confounding factor in large-scale clinical trials that aim to determine the overall effectiveness of a medication.
Personalized medicine, an approach that customizes medical care using information about an individual’s genetic, proteomic (proteins) or metabolic, profile provides an integrated approach to better identify treatments appropriate to an individual’s needs without going through an extensive period of trial and error. Pharmacogenetics is one methodology that uses an individual’s genetic profile to determine a person’s potential responsiveness to a medication and the likelihood of an adverse response.
Two recent pharmacogenetic studies of commonly used medications in autism indicate that genetic profiles may hold promise in identifying those who would respond well and those likely to have side-effects. A study by a team in Portugal examined how variations in eight candidate genes may help estimate levels of improvement with the use of risperidone and those most at risk for increased weight gain – a problematic side effect of this treatment. Risperidone is an atypical anti-psychotic and one of two drugs with a specific indication to treat irritability and maladaptive behaviors associated with autism. These eight genes are key in the biological systems involved in drug metabolism (how the body uses the drug) and pharmacodynamics (what the drug does to the body). Four gene variations (called polymorphisms) were found to be predictive of clinical improvement. Two others were indicative of those at risk of increased weight gain. Another study, by a team at the University of Illinois, Chicago, examined genes applicable to the drug Escitalopram, which belongs to the class of drugs called selective serotonin reuptake inhibitors (SSRIs). SSRIs have been indicated in clinical practice and smaller clinical trials as effective treatments for repetitive behaviors; larger clinical trials, however, have not demonstrated positive effect, potentially due to individual differences within the study group. This study looked at genetic variations of a serotonin gene involved with the specific targets of the SSRI medications. The researchers found that one variation was associated with a smaller reduction in irritability scores.
These studies are among the few pharmacogenetic studies that have been conducted for autism, and additional larger scale studies are needed to confirm these findings. Nonetheless, these studies confirm the potential for pharmacogenetics to refine research approaches to treatment trials in ASD. This research is an important first step for developing more personalized treatments for individuals with autism.
Owley et al. (2009) A pharmacogenetic study of Escialopram in Autism Spectrum Disorders. Autism Research. 2: 1-7.
Correia, CT et al. (2009). Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions. Pharmacogenomics J. Dec 8. doi: 10.1038/tpj.2009.63
