Inefficient dystrophin expression after cord blood transplantation in Duchenne muscular dystrophy

• Published in: Muscle & nerve 2010-06, Vol.41 (6), p.746-750
• Main Authors: Kang, Peter B., Lidov, Hart G.W., White, Alexander J., Mitchell, Matthew, Balasubramanian, Anuradha, Estrella, Elicia, Bennett, Richard R., Darras, Basil T., Shapiro, Frederic D., Bambach, Barbara J., Kurtzberg, Joanne, Gussoni, Emanuela, Kunkel, Louis M.
• Format: Article
• Language: English
• Subjects: Alemtuzumab; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - therapeutic use; Biological and medical sciences; Child; Chromosome Mapping; Chromosomes, Human, X; chronic granulomatous disease; Cyclophosphamide - therapeutic use; Diseases of striated muscles. Neuromuscular diseases; Duchenne muscular dystrophy; dystrophin; Dystrophin - deficiency; Dystrophin - genetics; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Expression Regulation; Granulomatous Disease, Chronic - genetics; Granulomatous Disease, Chronic - surgery; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Male; Medical sciences; Muscular Dystrophy, Duchenne - genetics; Muscular Dystrophy, Duchenne - surgery; Neurology; Reoperation; stem cell therapy; Striated muscle. Tendons; Transplantation, Homologous; Treatment Outcome; umbilical cord blood transplantation; Vertebrates: osteoarticular system, musculoskeletal system; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.21702

We report a boy who received two allogeneic stem cell transplantations from umbilical cord donors to treat chronic granulomatous disease (CGD). The CGD was cured after the second transplantation, but 2.5 years later he was diagnosed with Duchenne muscular dystrophy (DMD). Examinations of his DNA, muscle tissue, and myoblast cultures derived from muscle tissue were performed to determine whether any donor dystrophin was being expressed. The boy was found to have a large‐scale deletion on the X chromosome that spanned the loci for CYBB and DMD. The absence of dystrophin led to muscle histology characteristic of DMD. Analysis of myofibers demonstrated no definite donor cell engraftment. This case suggests that umbilical cord–derived hematopoietic stem cell transplantation will not be efficacious in the therapy of DMD without additional interventions that induce engraftment of donor cells in skeletal muscle. Muscle Nerve, 2010