Evaluation of long-term cardiac MRI outcome following micro-dystrophin gene therapy in subjects with Duchenne muscular dystrophy receiving SGT-001


Clinical Trials

Poster Number: M184


Stephanie Salabarria, BHSc, University of Florida, Renata Shih, MD, University of Florida, Carmen Leon, MD, U of Florida, Tina Cousins, BS, RDCS, University of Florida, Julie Berthy, DNP, University of Florida, Manuela Corti, PT, PhD, University of Florida, Glenn Walter, PhD, University of FL Department of Physiology and Aging, Faris Al-Mousily, MD, Arnold Palmer, Barry Byrne, MD, PhD, University of Florida

Background: Micro-dystrophin gene replacement therapies for Duchenne muscular dystrophy (DMD) have not been thoroughly investigated for their efficacy in preventing or delaying the cardiac manifestations of DMD. Adeno-associated viral serotype 9 (AAV9) has shown to have effective cardiomyocyte transduction following intravenous administration preventing cardiac strain abnormalities and maintaining normal (>55%) ejection fraction (EF) in preclinical models. Here we present long term cardiac imaging resonance imaging (cMRI) data on seven subjects dosed in the Solid Biosciences IGNITE DMD Phase I/II trial using SGT-001, an AAV9 micro-dystrophin therapy.

Methods: Review of cMRI findings of subjects in the IGNITE DMD study at the University of Florida. cMRIs were obtained using a standardized protocol at Baseline and yearly up to Year-5 with a 3T/60cm Siemens Prisma scanner. Images were analyzed using Medis Cardiac Imaging. cMRIs from baseline and yearly up to year 5 after dosing were included. Subjects with 2 or more cMRIs were included.

Results: Seven participants met criteria. All subjects were white males, median age (range) at dosing was 7y (5-14) and had a median BMI (range) of 17.9 (17.6-26.0). One participant was non-ambulant and six were ambulant at the time of dosing. Participant 1-3 received the low-dose of SGT-001 (5E13 vg/kg) and particpants 4-7 received the high-dose (2E14 vg/kg). All were on a daily steroid regimen and under standard cardiac care. Ejection fraction (EF) remained within normal range for subjects 2-7, median 61.8% (51-72). The oldest particpant (14y, Subject 1) exhibited a decreased EF at Year 5 (39%) when compared to his pre-treatment EF (50.9%), however, had near normal left ventricle (LV) endo Global circumferential strain (GCS)% at Year 3 (–16.95). LVEDV was normal in participants 2-7 throughout the duration of the study, median 67.2 mL/m2 (56 -108 mL/m2). Subject 1 showed an increased LVEDV at Year 5 of 118.76 mL/m2 vs. 94.7 mL/m2 pre-treatment.

Conclusion: This is the first study that describes longitudinal cMRI findings in DMD subjects that have received micro-dystrophin gene therapy. We observed that cardiac function was preserved as the individuals age with expected worsening of DMD-related cardiomyopathy. Further studies are needed to better understand the effects of the DMD gene therapy in the heart and carefully quantify the extent of cardiac gene transfer.