Improved Muscle Quality in Duchenne Muscular Dystrophy With SRP-9001

Boys with Duchenne muscular dystrophy (DMD) who received SRP-9001 gene therapy had minimal fat infiltration, minimal fat peak, and bulk magnetic resonance imaging (MRI) transverse relaxation time (qT₂) compared with participants in a natural history cohort, according to study findings published in JAMA Network Open.

Gene therapy showed promise in a study of DMD with robust transgene expression on muscle biopsy; as a result, study researchers sought to discover whether SRP-9001 would aid large muscle groups, as measured with quantitative magnetic resonance imaging (qMRI) and spectroscopy (qMRS).

A total of 3 case-control study participants with a mean age of 6.8 years in the Systemic Gene Delivery Clinical Trial for DMD (NCT03375164) volunteered for qMRI and qMRS evaluation at the University of Florida between 2018 and 2020. They were imaged after systemic delivery of SRP-9001, between 6 and 24 months after treatment, using the magnetic resonance (MR) protocols in the Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy (ImagingDMD) study (NCT01484678).

A cohort of 54 participants from the ImagingDMD study age-matched with the SRP-9001 recipients was drawn retrospectively and treated with corticosteroids instead of SRP-9001. The study researchers retrospectively identified 17 age-matched individuals without DMD for a comparison control cohort.

They acquired multi-echo axial gradient echo images and multi-echo spin echo images in the calves and thighs and localized single-voxel proton MRS (1H-MRS) in the vastus lateralis (VL) and soleus muscles.

The boys who received SRP-9001 had minimal fat infiltration and minimal visible fat peak on MR images compared with the participants in the natural history cohort (value, 0.13). They also had mean [standard deviation or SD] VL MRS fat function similar to that of participants in the control cohort (both 0.02 [0.01] and less than that of participants in the natural history cohort, 0.11 [0.11]).

VL fat fraction was stable over 12 months in 2 boys who received SRP-9001 and had repeated measurements (mean [SD] change = 0.00 [0.01]). The 42 participants in the natural history cohort with repeated measurements did not have stable VL fat fraction (mean [SD] change = 0.05 [0.07]).

Mean qT₂ across 5 upper and lower leg muscles was greater in participants in the natural history cohort (44.7 [7.7] ms) than in participants in the SRP-9001 (37.3 [2.2] ms) or control cohorts (35.1 [3.7] ms).

Limitations of the study included small sample size and lack of MR data before gene therapy.

“These data support previously published histological and functional evidence for milder disease involvement following gene replacement in DMD,” the study researchers concluded.

Disclosure: Multiple study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Willcocks RJ, Forbes SC, Walter GA, et al. Assessment of rAAVrh.74.MHCK7.micro-dystrophin gene therapy using magnetic resonance imaging in children with Duchenne muscular dystrophy. JAMA Netw Open. 2021;4(1): e2031851. doi:10.1001/jamanetworkopen.2020.31851