Methods of Generating Mature Human Muscle Fibers

Abstract

The invention relates to methods of treating a subject having a muscle disorder by identifying a subject having a muscle disorder in need of treatment; injecting human myogenic precursor cells in an amount capable of forming mature muscle tissue into a portion of a limb of the subject; subjecting a nerve of the limb to therapeutic stimulation configured to enhance engraftment of the human myogenic precursor cells; and creating a graft of the human myogenic precursor cells to promote generation of mature muscle tissue, wherein the generation of mature muscle tissue improves muscle function. Preferably, the subject is a mammal, such as a human or a non-human mammal. In some embodiments, the non-human mammal is immunocompromised and the limb is irradiated. The engraftment can be promoted by a means other than therapeutic electrical stimulation (preferably intermittent neuromuscular electrical stimulation), for example by exercise.

1 . A method of treating a subject having a muscle disorder comprising the steps of:
 a) identifying a subject having a muscle disorder in need of treatment;   b) injecting human myogenic precursor cells in an amount capable of forming mature muscle tissue into a portion of a limb of the subject;   c) subjecting a nerve of the limb to therapeutic stimulation configured to enhance engraftment of the human myogenic precursor cells; and   d) creating a graft of the human myogenic precursor cells to promote generation of mature muscle tissue,   
       wherein the generation of mature muscle tissue improves muscle function. 
     
     
         2 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         3 . The method of  claim 2 , wherein if the subject is a non-human mammal, the non-human mammal is immunocompromised and the limb is irradiated. 
     
     
         4 . The method of  claim 2 , wherein the mammal is a human. 
     
     
         5 . The method of  claim 1 , wherein the therapeutic stimulation is therapeutic electrical stimulation. 
     
     
         6 . The method of  claim 1 , wherein engraftment is promoted by a means other than therapeutic electrical stimulation. 
     
     
         7 . The method of  claim 1 , wherein engraftment is promoted by exercise. 
     
     
         8 . The method of  claim 1 , wherein the muscle disease is selected from the group consisting of: acid maltase deficiency (AMD), Andersen-Tawil Syndrome, Becker Muscular Dystrophy (BMD), Becker Myotonia Congenita, Bethlem Myopathy, Bulbospinal Muscular Atrophy (Spinal-Bulbar Muscular Atrophy), Carnitine Deficiency, Central Core Disease (CCD), Centronuclear Myopathy, Charcot-Marie-Tooth Disease (CMT), Congenital Muscular Dystrophy (CMD), Congenital Myotonic Dystrophy, Dejerine-Sottas Disease (DSD), Dermatomyositis (DM), Distal Muscular Dystrophy (DD), Duchenne Muscular Dystrophy (DMD), Dystrophia Myotonica (Myotonic Muscular Dystrophy), Emery-Dreifuss Muscular Dystrophy (EDMD), Eulenberg Disease (Paramyotonia Congenita), Facioscapulohumeral Muscular Dystrophy (FSH or FSHD), Finnish (Tibial) Distal Myopathy, Friedreich's Ataxia (FA), Fukuyama Congenital Muscular Dystrophy, Glycogenosis Type 2, Glycogenosis Type 5, Glycogenosis Type 7, Glycogenosis Type 9, Gowers-Laing Distal Myopathy, Hauptmann-Thanheuser MD (Emery-Dreifuss Muscular Dystrophy), Hereditary Inclusion-Body Myositis, Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease), Hyperthyroid Myopathy, Hypothyroid Myopathy, Inclusion-Body Myositis (IBM), Inherited Myopathies, Integrin-Deficient Congenital Muscular Dystrophy, Kennedy Disease (Spinal-Bulbar Muscular Atrophy), Kugelberg-Welander Disease (Spinal Muscular Atrophy), Lactate Dehydrogenase Deficiency, Lambert-Eaton Myasthenic Syndrome (LEMS), Limb-Girdle Muscular Dystrophies (LGMDs), Lou Gehrig's Disease (Amyotrophic Lateral Sclerosis), Merosin-Deficient Congenital Muscular Dystrophy, Metabolic Diseases of Muscle, Mitochondrial Myopathy, Miyoshi Distal Myopathy, Motor Neurone Disease, Muscle-Eye-Brain Disease, Myasthenia Gravis (MG), Myofibrillar Myopathy, Myotonia Congenita (MC), Myotonic Muscular Dystrophy (MMD), Myotubular Myopathy (MTM or MM), Nemaline Myopathy, Nonaka Distal Myopathy, Oculopharyngeal Muscular Dystrophy (OPMD), Paramyotonia Congenita, Periodic Paralysis, Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease), Pompe Disease (Acid Maltase Deficiency), Progressive External Ophthalmoplegia (PEO), Rod Body Disease (Nemaline Myopathy), Spinal Muscular Atrophy (SMA), Spinal-Bulbar Muscular Atrophy (SBMA), Steinert Disease (Myotonic Muscular Dystrophy), Thomsen Disease (Myotonia Congenita), Ullrich Congenital Muscular Dystrophy, Walker-Warburg Syndrome (Congenital Muscular Dystrophy), Welander Distal Myopathy, and Werdnig-Hoffmann Disease (Spinal Muscular Atrophy). 
     
     
         9 . The method of  claim 5 , wherein the therapeutic electrical stimulation is preferably intermittent neuromuscular electrical stimulation.