Untying Knots of ASD and Associated Syndrome

understanding autism: untying knots

Autism spectrum disorder (ASD) is like a dense bundle of knots. Getting to its core can only be done by unraveling the complexities of numerous syndromes that are linked to ASD, one by one.

Doctor Alexander Kolevzon is currently working to comprehend Phelan-McDermid syndrome (PMS). A clinical director at Mount Sinai, Kolevzon directed a pilot study that aimed to improve the social impairments of those suffering of PMS, many of which also have ASD. The study was originally published in the December 12 issue of the journal Molecular Autism.

“Because different genetic causes of ASD converge on common underlying chemical signaling pathways, the findings of this study may have implications for many forms of ASD,” Kolevzon reported. The chemical signaling pathways he refers to involve the role of SHANK3, a gene found on chromosome 22. SHANK3 is highly involved in synapses, the gaps between neurons through which chemical messages are passed to reach individual target cells. Mutations and deletions of the gene cause developmental and language delays, as well as poor motor skills.

While the deletion or mutation of the gene causes PMS, it has remained unclear whether there exists a link between variations of the gene and autism until now. Mount Sinai’s preclinical study persuaded Doctor Kolevzon that a link exists, and inspired the hospital to conduct the first controlled trial of any treatment for PMS. Using SHANK3 deficient mouse models and neuronal models of SHANK3 deficient humans, the preclinical study indicated that reversal of synaptic plasticity and motor learning deficits may occur due to insulin-like growth factor-1, or IGF-1. IGF-1 is highly involved in synaptic transmission; it boosts synaptic circuits viability by promoting nerve cell survival and synaptic maturation. In addition, IFG-1 increases synaptic plasticity, the tendency for synaptic connections to change in structure and function to efficiently process novel stimuli.

The Mount Sinai placebo-controlled, double-blind study exposed nine PMS-suffering children, ages 5 to 15, to three months of IGF-1 treatment and three months of placebo. The order of treatment was random. Major improvements were observed during the IGF-1 phase as opposed to the placebo phase. Specifically, the children showed fewer signs of social withdrawal and restrictive behaviors, two indicators that standard behavior scales such as the Aberrant Behavior Checklist and the Repetitive Behavior Scale employ when assessing the effects of ASD treatments. Thus, the study became the first to explore the probability that the growth hormone IGF-1 can greatly ameliorate social impairment linked with ASD.

This study is just the beginning. Improving PMS symptoms helps untangle the cluster of knots that is ASD. Joseph Buxbaum, PhD, Professor of Psychiatry, Genetics and Genomic Sciences and Neuroscience at Mount Sinai, affirmed that “this clinical trial is part of a paradigm shift to develop targeted, disease modifying medicines specifically to treat the core symptoms of ASD.”

Maude Plucker, Tufts University