Nemaline Myopathy Natural History: A Multicenter, Longitudinal, Prospective Cohort Study


Clinical Trials

Poster Number: M231


Cara Piccoli, MD, Stanford University Medical Center, Tina Duong, PT, PhD, Stanford University Medical Center, John Day, MD, PhD, Stanford University Medical Center, Lesly Hayes, MD, Boston Children's Hospital, Alan Beggs, PhD, Boston Children's Hospital / Harvard Medical School, Carsten Bonnemann, MD, PhD, National Institutes of Health, Reghan Foley, MD, National Institutes of Health, Kaitlin Batley, MD, UT Southwestern, Richard Finkel, MD, St. Jude Children’s Research Hospital, James Dowling, MD, PhD, Hospital for Sick Children, Laurent Servais, MD, PhD, Oxford University, Charlotte Lilien, MPT, Oxford University, Gemma Fisher, MBChB, MRCPCH, Oxford University, Ana Carolina Tesi Rocha, MD, Stanford University

Nemaline myopathy (NM) is a rare and severe muscle disease associated with impaired skeletal muscle contractile function, muscle weakness, and significant disabilities. Typically, NM presents in infancy or early childhood with common features including hypotonia, diffuse weakness, and delayed motor milestones, but later onset phenotypes exist. Currently, there are no specific treatments or disease modifying therapies for any aspect of the disease process, despite active research. In the current care model for NM, critical barriers include: (1) a lack of disease natural history for all subtypes, and (2) a lack of established outcome measures suitable for interventional clinical trials. In addition, there is currently no formal network of clinical care centers working towards establishing these critical data points. This study was designed to establish a clinical research network for NM and to use this network to define disease natural history and clinical outcome measures.

The primary goal of this study is to define disease natural history and clinical outcome measures to inform future clinical trials.

Study Design:
This is a multicenter, prospective, longitudinal natural history study for patients with NM. There are currently 7 sites participating across North America and Europe. Patients ages 0-18 with ACTA1- or NEB-related NM will be enrolled with a goal sample size of 50 patients (~25 ACTA1 and ~25 NEB), with approximately 5-10 patients per site. Enrollment begins January 2024. There will be in-person assessments every 6 months for children >12 months, and every 3 months for infants <12 months. Patients will be followed for 3 years. Outcome measures include medical assessments, age-appropriate and ambulatory-conscious clinical function scores, spirometry, ventilatory status, echocardiograms, electrocardiograms, serological markers, among others. There are additional site-specific outcomes measures as well, including wearables, actigraphy and lower extremity imaging. We anticipate that results will be available in 2028. Conclusions: This study will provide comprehensive information for clinicians to prognosticate, treat and serve patients with NM. We are establishing an international clinical research network to create cohesion and optimal care for this patient population. We hope to inform the MDA community of this study in order to encourage referrals and involvement in this study.