Autologous Myoblast Transplantation for Oculopharyngeal Muscular Dystrophy: a Phase I/Iia Clinical Study

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant genetic disease mainly characterized by ptosis and dysphagia. We conducted a phase I/IIa clinical study (ClinicalTrials.gov NCT00773227) using autologous myoblast transplantation following myotomy in adult OPMD patients. This study included 12 patients with clinical diagnosis of OPMD, indication for cricopharyngeal myotomy, and confirmed genetic diagnosis. The feasibility and safety end points of both autologous myoblast transplantation and the surgical procedure were assessed by videoendoscopy in addition to physical examinations. Potential therapeutic benefit was also assessed through videoendoscopy and videofluoroscopy of swallowing, quality of life score, dysphagia grade, and a drink test. Patients were injected with a median of 178 million myoblasts following myotomy. Short and long-term (2 years) safety and tolerability were observed in all the patients, with no adverse effects. There was an improvement in the quality of life score for all 12 patients, and no functional degradation in swallowing was observed for 10 patients. A cell dose-dependant improvement in swallowing was even observed in this study. This trial supports the hypothesis that a local injection of autologous myoblasts in the pharyngeal muscles is a safe and efficient procedure for OPMD patients.

Current targeted therapeutic strategies for oculopharyngeal muscular dystrophy: from pharmacological to RNA replacement and gene editing therapies

“…Over the last few years, several potential treatment approaches have emerged [16,18,[32][33][34][35][36][37][38], some of which are described in Table 1. Given that these treatment strategies are limited to reducing the symptoms of the disease, it is vital that new therapies are developed that directly target the underlying mutation in OPMD.…”

Imagerie et spectroscopie par résonance magnétique nucléaire du muscle strié squelettique

“…La conformation anatomique ainsi que le mouvement respiratoire compliquent l'étude du diaphragme, mais son rôle fonctionnel et son implication dans de nombreuses maladies justifient ces efforts (Mead et al 2014). Un autre exemple, parmi une multitude : la thérapie cellulaire de patients atteints de dystrophie musculaire oculo-pharyngée (Périé et al 2014). Une imagerie de haute résolution des muscles laryngés injectés avec des myoblastes homologues pourrait permettre de suivre, sinon directement les cellules thérapeuti-ques éventuellement marquées avec un agent de contraste, tout au moins leur impact éventuel sur la progression des lésions dégénératives.…”

Concise Review: Mesoangioblast and Mesenchymal Stem Cell Therapy for Muscular Dystrophy: Progress, Challenges, and Future Directions

“…However, it might be feasible to use myoblast therapy to treat muscular dystrophies with fewer, small affected muscles, such as oculopharyngeal muscular dystrophy (OPMD) and facioscapulohumeral muscular dystrophy. In support of this possibility, a phase I/IIa trial of patients with OPMD was conducted [31]. They reported improvement in the quality of life for all patients (n = 12), a cell dose-dependent improvement in swallowing, no subsequent decline in swallowing after initial myotomy and cell transplantation, and no adverse events [31].…”

“…In support of this possibility, a phase I/IIa trial of patients with OPMD was conducted [31]. They reported improvement in the quality of life for all patients (n = 12), a cell dose-dependent improvement in swallowing, no subsequent decline in swallowing after initial myotomy and cell transplantation, and no adverse events [31]. Subsequent efforts have also focused on identifying other stem cell populations for regenerating dystrophic muscle, primarily myogenic stem cells that participate directly in muscle repair, although a recent study also demonstrated the importance of other cells such as regulatory T cells that indirectly influence this process in damaged muscle [32].…”