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An open-label study evaluating the safety and efficacy of AMO-01 for the treatment of seizures in Phelan-McDermid syndrome
Journal article   Open access   Peer reviewed

An open-label study evaluating the safety and efficacy of AMO-01 for the treatment of seizures in Phelan-McDermid syndrome

Tess Levy, J. Lloyd Holder, Joseph P. Horrigan, Michael F. Snape, Alison McMorn, Christina Layton, Hailey Silver, Kate Friedman, Hannah Grosman, Slayton Underwood, …
HGG advances, v 6(2), 100393
10 Apr 2025
DOI: https://doi.org/10.1016/j.xhgg.2024.100393
PMID: 39690738
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.xhgg.2024.100393View
Published, Version of Record (VoR) Open

Abstract

AMO-01 ASD autism spectrum disorder Phelan-McDermid syndrome PMS seizures shank3 Epilepsy
Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene. Approximately 25% of individuals with PMS have epilepsy. Treatment of epilepsy in PMS may require multiple anticonvulsants, and in a minority of cases, seizures remain poorly controlled. Converging lines of evidence in different experimental models indicate that the Ras-ERK pathway is implicated in the pathophysiology of seizure generation and neurobehavioral symptoms in PMS. The goal of this study was to evaluate the safety, tolerability, and efficacy in treating seizures in adults and adolescents with PMS using AMO-01, a Ras-ERK pathway inhibitor. A single 6-hour intravenous infusion of AMO-01 at 120 mg/m2 was administered to six participants using an open-label design. Safety was assessed during the infusion and for 4 weeks post-infusion. Caregivers completed seizure diaries and recorded individual seizures during a baseline period and for 4 weeks following the infusion. Exploratory clinical and biomarker assessments were completed throughout the study. AMO-01 was well tolerated, with no serious adverse events (AEs) reported. All AEs were mild or moderate in severity. Seizures were reduced by at least 25% compared to baseline at each follow-up (weeks 1, 2, and 4). Exploratory clinical measures did not change significantly from baseline, but visual evoked potentials (VEPs) and phosphorylated ERK blood levels revealed trending changes in a subset of participants. These results provide preliminary support for the safety of AMO-01 and its efficacy in reducing seizures in adults with PMS. Future placebo-controlled studies with larger sample sizes and repeated dosing are warranted. Phelan-McDermid syndrome is a neurodevelopmental disorder associated with seizures. Here, we used an investigational medication called AMO-01 to assess the safety of the medication and assess seizure reduction in participants with PMS. We found that the drug was safe and well-tolerated and was associated with a reduction of seizures in the participants.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Genetics & Heredity
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