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IGF-1 for Autism Associated with Phelan-McDermid Syndrome

Insulin-like growth factor improves symptoms in small study; suggests promising direction, but not itself appropriate for long-term use
May 14, 2014

In a small clinical trial with nine children who have Phelan-McDermid syndrome, three months of daily injections of insulin-like growth factor (IGF-1) improved social function and reduced repetitive behaviors. However, the powerful growth-stimulating hormone – approved to treat short stature related to IGF deficiency in children – may not be suitable for long-term use. Nor should it be used in teens or adults once their bones have stopped growing.

Researchers Joseph Buxbaum and Alexander Kolevzon, of New York City’s Seaver Autism Center, announced the early results of their pilot study today at the International Meeting for Autism Research (IMFAR). They also described promising results from a related study using a mouse model of autism. The Seaver Center is part of the Icahn School of Medicine at Mount Sinai.

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“IGF-1 may not be appropriate for long-term use because of the risks of peripheral growth,” Dr. Kolevzon says. “Instead, this would support the exploration of other medicines that act as growth factors and perhaps also stimulate IGF-1 release in the brain.” Ongoing treatment would probably be necessary to maintain benefits, he adds.

The promise of gene-targeted treatments
“Importantly, this study shows how genetics can guide the development of targeted treatments for different subtypes of autism,” comments developmental-behavioral pediatrician Paul Wang, Autism Speaks head of medical research. “We believe this is one of the approaches that will produce promising new treatments,” he says. Dr. Wang was not involved in the study.

The SHANK3 gene and autism
Phelan-McDermid syndrome is a rare disorder that frequently includes autism. It’s caused by deletions or mutations in the SHANK3 gene. In previous research, Dr. Buxbaum found that IGF-1 has beneficial effects on the development of brain nerve cells with the SHANK3 mutation. Still other studies suggest that SHANK3 and the brain-cell processes that it controls may play a role in some other forms of autism as well.

A small pilot study
In the Mount Sinai study, nine children (ages 5 to 15) with Phelan-McDermid syndrome and autism each received three months of daily injections with IGF-1 and three months of placebo in random order. In between, they went through a four-week “wash-out” period with no injections.

Compared to the placebo, the IGF-1 treatment significantly improved social behavior according to a standardized measure (Aberrant Behavior Checklist Social Withdrawal subscale). It also produced significant reductions in repetitive behaviors.

The researchers hope to enroll another 18 children in the trial before its completion.

Insights from related mouse study
In their related animal study, the researchers used a mouse model of autism they developed by knocking out its SHANK3 gene. Daily injections of IGF-1 reversed the mice’s impaired brain nerve cell signaling. The treatment also improved their ability to perform a motor skills test (staying on a bar that rotates at increasing speed).

Families cautioned to wait for further testing
Some families already use over-the-counter supplements containing a form of IGF from deer antlers as an alternative treatment for autism. Dr. Kolevzon cautions against such products: “Over-the-counter IGF-1 products probably don’t cross the blood-brain barrier,” he says. Nor have they been rigorously tested for safety – or even the consistency of what they contain.

Dr. Kolevzon likewise cautions against the off-label use of prescription IGF-1 for autism outside of a carefully controlled study. “We have a lot more to learn about the safety, tolerability and efficacy of IGF-1,” he says. “We strongly encourage families to wait for the results of our full study.”

Watch Dr. Joseph Buxbaum discuss the study at the IMFAR opening press conference below.



Read more news and perspective from IMFAR 2014, click here.