Case report Assessment of a symptomatic Duchenne muscular dystrophy carrier 20 years after myoblast transplantation from her asymptomatic identical twin sister Jean-Yves Hogrel a,⇑ , Fabien Zagnoli b , Aure ´lie Canal a , Bodvael Fraysse a , Jean-Pierre Bouchard c , Daniel Skuk c , Michel Fardeau a , Jacques P. Tremblay c a Institut de Myologie, GH Pitie ´-Salpe ˆtrie `re, Paris, France b Ho ˆpital d’Instruction des Arme ´es Clermont-Tonnerre, Brest, France c Universite ´ Laval, Que ´bec, Canada Received 25 September 2012; received in revised form 11 February 2013; accepted 30 April 2013 Abstract Because it is due to a mutation on the X-chromosome, Duchenne muscular dystrophy rarely affects women, unless there is an unequal lyonisation of the X-chromosome containing the normal dystrophin gene. We report here the unique situation of a symptomatic Duchenne muscular dystrophy woman who was transplanted with myoblasts received from her asymptomatic monozygotic twin sister 20 years ago. Specific dynamometry was performed to possibly detect a long-term effect of this cell therapy. Long-term safety of myoblast transplantation was established by this exceptional case. However, long-term efficacy could not be definitively asserted for this patient, in spite of several clues suggesting beneficial effects. Ó 2013 Elsevier B.V. All rights reserved. Keywords: Duchenne muscular dystrophy; Cell therapy; Outcome measures; Monozygotic twin; Unequal lyonisation 1. Introduction Duchenne muscular dystrophy (DMD) is a hereditary disease due to the mutation of the dystrophin gene in the X-chromosome leading to the absence of dystrophin under the sarcolemma [1]. Females are usually asymptomatic DMD carriers; however a few symptomatic DMD cases have been reported in women [2–4]. The clinical manifestation of DMD in females has been attributed to a more frequent inactivation during lyonisation of the X-chromosome containing the normal dystrophin gene [3]. In female monozygotic twins, discordant manifestations of X-linked diseases occur frequently. This is apparently due to unequal lyonisation; the paternal X-chromosome being preferentially inactivated in one twin and the maternal X-chromosome preferentially inactivated in the other twin. Unequal severity of phenotype in identical twin DMD carriers has been reported a few times [5–9]. One of these cases [9] was a girl that had an identical twin who was an asymptomatic carrier, the difference being due to unequal lyonisation. Twenty years ago, our team transplanted myoblasts obtained from the healthy twin in the right biceps brachii and right extensor carpi radialis of the symptomatic twin. Results were published in 1993 in Neuromuscular Disorders [10]. Both sisters have been recently re-evaluated using specific dynamometry. This unique situation raised some interesting and crucial considerations related to cell therapy in particular and therapeutic trials in general. 0960-8966/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.nmd.2013.04.007 ⇑ Corresponding author. Address: Institut de Myologie, GH Pitie ´-Salpe ˆtrie `re, 75651 Paris Cedex 13, France. Tel.: +33 142165880; fax: +33 142165881. E-mail address: jy.hogrel@institut-myologie.org (J.-Y. Hogrel). www.elsevier.com/locate/nmd Available online at www.sciencedirect.com Neuromuscular Disorders 23 (2013) 575–579