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.

Figures

Figure 1

Pharyngeal propulsion preoperatively, and at 12 and 24 months observed by (a) videoendoscopic swallowing study and by (b) videofluoroscopy of swallowing. Parameters were scored as normal (0), decreased (I), or severely impaired with no peristaltic waves (II).

Figure 2

Upper esophageal sphincter (UES) function preoperatively, and at 12 and 24 months observed by (a) videoendoscopic swallowing study and by (b) videofluoroscopy of swallowing. UES function was evaluated by the quality of the UES opening and closure and on the salivary or diet pooling in the hypopharynx, results scored as normal (0) or abnormal (I).

Figure 3

Score of Salassa (a) ranging from grade 0 (normal) to grade V (extremely severed swallowing disorders) and questionnaire of McHorney (b) to evaluate symptoms and quality of life preoperatively or at different time point following the graft. Dotted lines indicate a normal deglutition. ANOVA and Dunnett's post-test (*P < 0.05 compared with preinclusion score).

Figure 4

Quantitative evaluation of the global swallowing using the time in seconds to swallow a glass of 80 ml of water. Dotted lines indicate the averaged standard value in the normal population (7s). ANOVA and Dunnett's post-test (NS non significant; *P < 0.05; **P < 0.01 compared with preinclusion score).

Figure 5

Correlation between the number of cells injected and the improvement of the time of swallowing. The percentage of swallowing improvement is determined between the time of swallowing preoperatively and each time point. 178 millions cells represent the median of the number of cells injected in this trial. Each group contains six patients, with no statistical difference in swallowing preoperatively. Mann-Whitney test (**P < 0.01).