Cardiosphere-derived cells (CDCs) successfully slowed muscle function impairment by up to 71% in patients with Duchenne muscular dystrophy (DMD), according to a new study published in The Lancet.

The multicenter, randomized, double-blind, phase 2 trial named HOPE-2 was conducted by McDonald and colleagues and included 26 male patients aged 10 years or older from 7 centers in the US. After some screen failures and resignations, the CDC and placebo group incorporated 7 and 9 patients, respectively. All participants had a DMD diagnosis with moderate upper limb impairment.

Disease progression was measured by comparing the mid-level elbow performance of upper limb version 1.2 (PUL 1.2) score before and after treatment at the first visit and after 12 months with a dose of 1.5 x10^8 CAP-1002 CDCs administered once every 3 months for 1 year.


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Patients who received CAP-1002 performed better at the mid-level elbow PUL 1.2 assessment vs those who received placebo in each follow-up, including at 3, 6, and 9 months, and at the 1-year assessment. Results were statistically significant with a percentile difference of 36.2, 95% CI 7.9–64.5; difference of 2.6 points; P =.014.

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CAP-1002 treatment produced adverse reactions in almost half of the patients; nevertheless, most were transitory hypersensibility reactions related to the administration, without long-term sequelae. One participant did experience a severe allergic reaction, forcing treatment discontinuation.

DMD’s pathogenesis consists of severe, progressive cardiac and skeletal muscle breakdown, which in turn generates an inflammatory response that sabotages muscle repairment. CDCs have antifibrotic and regenerative actions that aid in modulating the enhanced immune response seen in these patients, thus potentially impeding further muscle weakness.

Prior experimental studies reported CDC’s success in ameliorating muscle deterioration in mice. Due to the lack of definitive treatment for DMD, and the high morbidity and mortality of this disease, the results obtained in this publication are encouraging.

“Although heart failure is only one cause of mortality in [DMD], it is sufficiently impactful that attenuation of cardiomyopathy progression could logically be predicted to improve survival; this conjecture has been untestable until now given the paucity of agents that alter the course of [DMD] cardiomyopathy,” the authors concluded.

Reference

McDonald C, Marbán E, Hendrix S, et al. Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. Published online March 12, 2022. doi:10.1016/s0140-6736(22)00012-5