THERAPEUTIC APPROACHES AND PERSPECTIVE

1. THERAPEUTIC APPROACHES AND PERSPECTIVE

2. Over the last few years a range of approaches have been developed that aim to correct the genetic defect, restore functional expression of dystrophin, slow disease progression, and improve the life quality of DMD patients. • These can roughly be categorized into three classes — genetic, cell-based, and pharmacological approaches (药理方法)

3. Genetic • Gene transfer A functional dystrophin gene could be inserted into dystrophy muscle cells to compensate for the defective gene copy. Recombinant adeno- associated viruses (AAV) possess some advantages of conventional adnoviral and retroviral vectors and lentiviral vectors, and are increasingly being used to carry the mini-, micro-dystrophin, or utrophin genes into the skeletal and heart cells of mdx mice.

4. Gene modification The aim of gene modification is to change or repair gene mutations. Among the most promising approaches is exon skipping, which attempts to turn a Duchenne mutation into a less severe Becker form . There is a gene therapy method known as targeting repairing or chimeraplast, using a synthetic blend of DNA and the related RNA, which tricks the patient's own cells to repair the mutation. The chimeraplasts match the patients' own DNA except for where the mutation occurs, attach to the DNA, and then activate DNA repair mechanisms.

5. cell-based • Cell therapy（细胞治疗） Muscular satellite cells, which positioned between the plasma membrane and the surrounding basal membrane of mature muscle fibers, are considered to represent muscular stem cells. Satillite cells alone are sufficient to mediate extensive regeneration of damaged adult skeletal muscle in vivo. The efficacy of bone marrow cells, or even single hematopoietic（造血的） stem cells, in the repair of muscle injury has been extensively explored. MSCs can participate in myogenesis both in vitro and in vivo, regenerating myofibers and sublminar Pax-7+ satellite cells in mdx/nude mice.

6. Utrophin Utrophin is a protein with similar structure to dystrophin and can be found in high concentrations within muscle cells during fetal development. After birth the expression shifts to the neuromuscular junction. Substantially increasing levels of utrophin protein by introducing a utrophin gene driven by a constitutive or a muscle -pecific promoter (or using chemicals that upregulate the promoter acitvity of the endogenous utrophin gene) could prevent the pathology of muscular dystrophy.

7. Pharmacological approaches • A broad range of pharmacological strategies for DMD are being exploited. These include steroid treatment, maintaining calcium homeostasis, decreasing inflammation, increasing muscle strength, suppressing stop codons, upregulation of utrophin, and increasing muscle mass via modulation of growth/developmental factors.

8. PERSPECTIVE • Advances in understanding diseases in recent years have opened the door for therapeutic interventions. Research aiming to further reveal the properties of dystrophic muscle fibres and in stem cell biology will harness the clinical use of different therapeutic approaches. It is most likely that only a combination of multiple approaches will eventually lead to the development of treatments.