Autologous Myoblasts for the Treatment of Fecal Incontinence

Olivier Boyer (1, 2) , Valérie Bridoux (3, 4, 5, 6) , Camille Giverne (1, 2) , Aurélie Bisson (1, 2) , Edith Koning (7) , Anne-Marie Leroi (8, 4, 5, 6) , Pascal Chambon (9) , Justine Déhayes (1) , Stéphanie Le Corre (1) , Serge Jacquot (1, 2) , Dominique Bastit (10) , Jérémie Martinet (1, 2) , Estelle Houivet (11) , Jean-Jacques Tuech (3) , Jacques Bénichou (11) , Francis Michot (3)

1 Laboratoire d'immunologie et biothérapies [Rouen]
2 PANTHER - Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices
3 Service de Chirurgie Digestive [CHU Rouen]
4 ADEN - Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau
5 IRIB - Institute for Research and Innovation in Biomedicine
6 UNIROUEN UFR Santé - UNIROUEN - UFR Santé
7 Service de Radiologie [CHU Rouen]
8 Service de Physiologie Digestive, Urinaire, Respiratoire et de l'Exercice [CHU Rouen]
9 Laboratoire de Cytogénétique [CHU Rouen]
10 Etablissement français du sang [Rouen]
11 Unité de Biostatistiques [CHU Rouen]

Objective: The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study.
Summary of Background Data: Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option.
Methods: We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year.
Results: At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months.
Conclusions: Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.

Mots clés: Stem cells; Fecal incontinence; Cell therapy; Autologous myoblasts

Domaines: Hépatologie et Gastroentérologie

Olivier Boyer, Valérie Bridoux, Camille Giverne, Aurélie Bisson, Edith Koning, et al.. Autologous Myoblasts for the Treatment of Fecal Incontinence. Annals of Surgery, 2018, 267 (3), pp.443-450. ⟨10.1097/SLA.0000000000002268⟩. ⟨hal-02315465⟩