New research has found that a growth hormone can significantly improve the social impairment associated with autism spectrum disorder (ASD) in patients with a related genetic syndrome.
The pilot study, conducted at the Icahn School of Medicine at Mount Sinai, focused on the use of insulin-like growth factor-1 (IGF-1) to treat Phelan-McDermid syndrome (PMS), a disorder caused by a deletion or mutation of the SHANK3 gene on chromosome 22.
Along with facing developmental and language delays and motor skill deficits, most people with PMS also have autism spectrum disorder, according to the researchers.
SHANK3 is a focus of research in the field because of its essential role in the function of synapses, the gaps between nerve cells that “decide” whether messages continue along nerve pathways as they regulate bodily processes, the researchers explained.
While PMS is a rare disorder, advanced genetic technology has revealed it to be a relatively common cause of ASD, researchers add.
“Ours is the first controlled trial of any treatment for Phelan-McDermid syndrome,” said Alexander Kolevzon, M.D., clinical director of the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai.
“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.”
IGF-1 promotes nerve cell survival, synaptic maturation, and synaptic plasticity, the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity, according to the researchers. It is approved by the Food and Drug Administration for the treatment of short stature.
Findings from the Mount Sinai study suggest that IGF-1 is safe, tolerable, and associated with significant improvement in both social impairment and restrictive behaviors, such as a fascination with one subject or activity; strong attachment to one specific object; preoccupation with part of an object rather than the whole object; or preoccupation with movement or things that move, in people with PMS.
The Mount Sinai researchers enrolled nine children between the ages of five and 15 who were diagnosed with PMS in a placebo-controlled, double-blind, cross-over design study. All the children were exposed to three months of treatment with IGF-1 and three months of placebo, in random order.
The study found that the IGF-1 phase was associated with significant improvements in social withdrawal and restrictive behaviors as measured by the Aberrant Behavior Checklist and the Repetitive Behavior Scale, both standard behavior scales used to assess treatment effects in ASD.
Preclinical studies of mice with deficient SHANK3 developed at Mount Sinai and human neuronal models derived from pluripotent stem cells — stem cells that have the capacity to produce several distinct biological responses — of humans with SHANK3 deficiency previously suggested that IGF-1 can reverse synaptic plasticity and motor learning deficits, the researchers noted.
These studies formed the basis for this clinical trial. The trial’s results provide support for the ongoing effort to develop related drug treatments, according to the researchers.
“This clinical trial is part of a paradigm shift to develop targeted, disease modifying medicines specifically to treat the core symptoms of ASD,” said Joseph Buxbaum, Ph.D., director of the Seaver Autism Center and a professor of psychiatry, genetics and genomic sciences and neuroscience at Mount Sinai.
“Results from this pilot trial will facilitate larger studies that more definitively inform efficacy and better targeted therapeutic treatments.”
This study, funded by the Beatrice and Samuel A. Seaver Foundation and by the National Institute of Mental Health, was published in the journal Molecular Autism.
Source: Mount Sinai Health System