Philip Ord Isaac Lalich DUCHENNE MUSCULAR DYSTROPHY (DMD)

 A patient with Duchenne muscular dystrophy.

 A Type of Muscular Dystrophy  Categorized Under Neuromuscular Diseases  Most Common form of Muscular Dystrophy  Affects 1:3500 Males  45,000 in U.S  996,000 Worldwide  Diagnosed with Blood Test or Biopsy  Characteristics  Weakness  Swollen Calve Muscles  Strange Gait  Muscle Wasting  Loss of Ambulation  Respiratory Insufficiency  Scoliosis  Cardiomyopathy (Some Cases) INTRODUCTION

 Dystrophin Gene  Locus: Xp21  X-Linked Recessive  Mutation Types  Point Mutation  Frameshift  Massive Missense  Premature Stop Codon (Nonsense)  Large Deletion  Location of Mutation Correlates with Severity  Extremely Large Gene  24 KB  3,685 AA GENETIC INFORMATION

 Structural Protein  Links Actin to the Extra-Cellular Matrix  Gives Cell Rigidity  Cell is Destroyed with Muscle Contraction  Muscle Cells Stop Regenerating MOLECULAR DESCRIPTION

 (1836)  Meryon (1852)  Guillame Duchenne (1868)  DMD is a severe disease, patients pass in their late 20s to early 30s.  However medical science is making leaps and bounds. BRIEF HISTORY

 Overall skeletal muscle deterioration.  Use of an electric wheelchair.  Some patients develop cardiomyopathy.  Scoliosis due to weakened back and trunk muscles.  Osteoporosis due to lack of weight bearing.  Muscle atrophy.  Respiratory insufficiency: eventual need for ventilator.  Prone to respiratory infection. CLINICAL CONSEQUENCES Retrieved from: th/article ece

 Corticosteroid Therapy  Prednisone  Deflazacourt  Side Effects Severe  Weight Gain  Cushinoid Appearance  Emotional Issues  Delayed Puberty  Stunted Growth  Cataracts  Osteoporosis TREATMENT

 Introduction of Myoblasts  Allow gene complementation with healthy dystrophin.  But can trigger immune response.  Gene Replacement  Large gene makes it difficult.  Mini-dystrophin in viral vector.  Stop Codon Suppression  Use of aminoglycoside antibiotics.  Promotes read-through of premature stop codons.  Exon Skipping  Antisense oligonucleotides (AONs) interact with splicing machinery.  Diseased exon spliced out with neighboring introns, restores reading frame.  Upregulation of Utrophin  Utrophin is a protein very homologous to dystrophin.  Telomere Exhaustion  Myoblasts run out of telomere length, can’t replace damaged muscle.  Treatment with telomerases may be in order. RESEARCH

 Bianchi, M., Biggar, D., Bushby, K., Rogol, A., Rutter, M., & Tseng, B. (2011). Endocrine aspects of Duchenne muscular dystrophy. Neuromuscular Disorders: NMD, 21(4),  Bianchi, M., Mazzanti, A., Galbiati, E., Saraifoger, S., Dubini, A., Cornelio, F., & Morandi, L. (2003). Bone mineral density and bone metabolism in Duchenne muscular dystrophy. Osteoporosis International, 14(9),  Fairclough, R., Bareja, A., & Davies, K. (2011). Progress in therapy for Duchenne muscular dystrophy. Experimental Physiology, 96(11),  Guglieri, M., & Bushby, K. (2010). Molecular treatments in Duchenne muscular dystrophy. Current Opinion In Pharmacology, 10(3),  Hoffman, E., Brown, R., & Kunkel, L. (1987). Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell, 51(6),  Pradhan, S., Ghosh, D., Srivastava, N., Kumar, A., Mittal, B., Pandey, C., & Singh, U. (2006). Prednisolone in Duchenne muscular dystrophy with imminent loss of ambulation. Journal Of Neurology, 253(10),  Sacco, A., Mourkioti, F., Tran, R., Choi, J., Llewellyn, M., Kraft, P., Shkreli, M., Delp, S., Pomerantz, J., Artandi, S., & Blau, M. (2010). Short teleomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell, 147(7),  Sussman, M. (2002). Duchenne muscular dystrophy. The Journal Of The American Academy Of Orthopaedic Surgeons, 10(2), REFERENCES