title: 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.
authors.affiliation: 1] Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Assistance publique-Hôpitaux de Paris (APHP), Hôpital Tenon, Paris, France [2] Université Paris VI Pierre et Marie Curie, Paris, France [3] Thérapie des maladies du muscle strié/ Institut de Myologie, UM76, INSERM U974, Groupe hospitalier Pitié-Salpétrière, Paris, France [4] CNRS UMR 7215, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Périé
authors.affiliation: 1] Université Paris VI Pierre et Marie Curie, Paris, France [2] Thérapie des maladies du muscle strié/ Institut de Myologie, UM76, INSERM U974, Groupe hospitalier Pitié-Salpétrière, Paris, France [3] CNRS UMR 7215, Paris, France.
authors.forename: Capucine
authors.initials: C
authors.lastname: Trollet
authors.affiliation: 1] Université Paris VI Pierre et Marie Curie, Paris, France [2] Thérapie des maladies du muscle strié/ Institut de Myologie, UM76, INSERM U974, Groupe hospitalier Pitié-Salpétrière, Paris, France [3] CNRS UMR 7215, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.affiliation: Unité de Thérapie Cellulaire et CIC-BT501, Hôpital Saint Louis, Assistance publique-Hôpitaux de Paris (APHP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vanneaux
authors.affiliation: 1] Université Paris VI Pierre et Marie Curie, Paris, France [2] Thérapie des maladies du muscle strié/ Institut de Myologie, UM76, INSERM U974, Groupe hospitalier Pitié-Salpétrière, Paris, France [3] CNRS UMR 7215, Paris, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Mamchaoui
authors.affiliation: 1] Université Paris VI Pierre et Marie Curie, Paris, France [2] Thérapie des maladies du muscle strié/ Institut de Myologie, UM76, INSERM U974, Groupe hospitalier Pitié-Salpétrière, Paris, France [3] CNRS UMR 7215, Paris, France.
authors.forename: Belaïd
authors.initials: B
authors.lastname: Bouazza
authors.affiliation: Amiens Hospital, Hematology Department, Avenue René Laennec, 80054 Amiens Cedex 1, France.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Marolleau
authors.affiliation: Service de Neurologie, Consultation de Pathologies Neuromusculaires, Institut de myologie, Hôpital Pitié Salpêtrière, Faculté de Médecine & Université Paris VI Pierre et Marie Curie, Assistance publique-Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforêt
authors.affiliation: CHU de Caen, Centre de Compétences des Pathologies Neuro-musculaires, Service de Médecine Physique et Réadaptation, Avenue de la Côte de Nacre, CS 30001, 14033 CAEN CEDEX 9, France et INSERM, U 1075 COMETE, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Chapon
authors.affiliation: Service de Neurologie, Consultation de Pathologies Neuromusculaires, Institut de myologie, Hôpital Pitié Salpêtrière, Faculté de Médecine & Université Paris VI Pierre et Marie Curie, Assistance publique-Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.affiliation: 1] Université Paris VI Pierre et Marie Curie, Paris, France [2] Thérapie des maladies du muscle strié/ Institut de Myologie, UM76, INSERM U974, Groupe hospitalier Pitié-Salpétrière, Paris, France [3] CNRS UMR 7215, Paris, France.
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.affiliation: Unité de Thérapie Cellulaire et CIC-BT501, Hôpital Saint Louis, Assistance publique-Hôpitaux de Paris (APHP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Jérome
authors.initials: J
authors.lastname: Larghero
authors.affiliation: 1] Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Assistance publique-Hôpitaux de Paris (APHP), Hôpital Tenon, Paris, France [2] Université Paris VI Pierre et Marie Curie, Paris, France [3] Thérapie des maladies du muscle strié/ Institut de Myologie, UM76, INSERM U974, Groupe hospitalier Pitié-Salpétrière, Paris, France [4] CNRS UMR 7215, Paris, France.
authors.forename: Jean Lacau
authors.initials: JL
authors.lastname: St Guily
mesh_terms: D000368:Aged; D049631:Esophageal Sphincter, Upper / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D039141:Muscular Dystrophy, Oculopharyngeal / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D010609:Pharyngeal Muscles / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D014182:Transplantation, Autologous; D016896:Treatment Outcome