A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome

S Sethuram, T Levy, J Foss-Feig, D Halpern, S Sandin, P M Siper, H Walker, J D Buxbaum, R Rapaport, A Kolevzon, S Sethuram, T Levy, J Foss-Feig, D Halpern, S Sandin, P M Siper, H Walker, J D Buxbaum, R Rapaport, A Kolevzon

Abstract

Background: Phelan-McDermid syndrome (PMS) is caused by 22q13 deletions including SHANK3 or pathogenic sequence variants in SHANK3 and is among the more common rare genetic findings in autism spectrum disorder (ASD). SHANK3 is critical for synaptic function, and preclinical and clinical studies suggest that insulin-like growth factor-1 (IGF-1) can reverse a range of deficits in PMS. IGF-1 release is stimulated by growth hormone secretion from the anterior pituitary gland, and this study sought to assess the feasibility of increasing IGF-1 levels through recombinant human growth hormone (rhGH) treatment, in addition to establishing safety and exploring efficacy of rhGH in children with PMS.

Methods: rhGH was administered once daily for 12 weeks to six children with PMS using an open-label design. IGF-1 levels, safety, and efficacy assessments were measured every 4 weeks throughout the study.

Results: rhGH administration increased levels of IGF-1 by at least 2 standard deviations and was well tolerated without serious adverse events. rhGH treatment was also associated with clinical improvement in social withdrawal, hyperactivity, and sensory symptoms.

Limitations: Results should be interpreted with caution given the small sample size and lack of a placebo control.

Conclusions: Overall, findings are promising and indicate the need for larger studies with rhGH in PMS. Trial registration NCT04003207. Registered July 1, 2019, https://ichgcp.net/clinical-trials-registry/NCT04003207 .

Keywords: ASD; Autism spectrum disorder; Growth hormone; IGF-1; Insulin-like growth factor-1; PMS; Phelan–McDermid syndrome; Shank3.

Conflict of interest statement

AK receives research support from AMO Pharma and consults to Acadia, Alkermes, Jaguar, Neuren, GW Pharma, and Ovid Therapeutics. JDB has a shared patent with Mount Sinai for IGF-1 in Phelan–McDermid syndrome. No other authors have competing interests to disclose.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Domains of clinical improvement. Lower ABC scores indicate improved behavior, and higher SSP scores indicate improved behavior

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