Breaking Through Autism

The Center for Disease Control and Prevention has found that 1 in 88 people are affected by autism spectrum disorders (ASD), a disorder four times more common in boys than in girls. At the Seaver Autism Center for Research and Treatment, we are dedicated to discovering the biological causes of ASD and developing breakthrough treatments. Through molecular genetics, model systems, and experimental therapeutics, we strive to translate scientific research into optimal community care.

Our understanding of the genetic basis of autism and related conditions has changed recently. Based on discoveries made by large genetic consortia including the Autism Sequencing Consortium (ASC) which we lead, we now know that autism can be conceived of as having multiple independent causes, where in many cases the cause can be largely attributed to a specific genetic mutation. The ASC expects to identify half of all ASD genes in the next several years, leading to better diagnosis and treatment.

Given this new view of subtypes of autism, the Seaver Autism Center runs a special program dedicated to a subtype of autism caused by a rare genetic mutation in which one copy of the SHANK3 gene is either missing or otherwise mutated. The SHANK3 gene is key to the development and function of the brain, and loss of SHANK3 impairs nervous system development and function.

Symptoms can vary, but typically the loss of SHANK3 (sometimes called 22q13 Deletion Syndrome or Phelan-McDermid Syndrome) is characterized by poor muscle tone, absent or delayed speech, intellectual disability, minor facial or body abnormalities, and ASD. SHANK3 mutations are estimated to occur in approximately 1% of patients with ASD.

As part of the Autism Clinical program, we conduct thorough phenotyping for each patient with a SHANK3 mutation in order to better understand the symptoms and implications of the disorder. In parallel we have disrupted Shank3 in mice and rats to study the impact on brain development and function. The genetically modified rat is a first rat model of Shank3 deficiency and ASD.

Recently, we tested the effects of Insulin-like Growth Factor-1 (IGF-1) on the mice with a Shank3 mutation. We found that IGF-1 was successful in treating brain and behavioral symptoms in the genetically modified mice, and we have since begun a clinical trial of IGF-1 in humans to evaluate the effectiveness of the drug on patients with a SHANK3 mutation.

This is the first time any neurobiologically defined medicine is being studied in humans for the treatment of the SHANK3 mutation. It will be very exciting to see the results of this pilot study come the summer of 2013.

Visit us at www.seaverautismcenter.org for more information about the Seaver Autism Center, or at www.shank3gene.org for SHANK3-specific research findings. We are on Facebook at www.facebook.com/seaverautismcenter!

Dr. Joseph Buxbaum – Director, Seaver Autism Center; Vice Chair for Research, Department of Psychiatry; Professor, Departments of Psychiatry, Genetics and Genomic Sciences, and Neuroscience

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