1 / 11

Duchenne muscular dystrophy (DMD)

Duchenne muscular dystrophy (DMD). Philip Ord Isaac Lalich. A patient with Duchenne muscular dystrophy. Introduction. Characteristics Weakness Swollen Calve Muscles Strange Gait Muscle Wasting Loss of Ambulation Respiratory Insufficiency Scoliosis Cardiomyopathy (Some Cases ).

oswald
Download Presentation

Duchenne muscular dystrophy (DMD)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Duchenne muscular dystrophy (DMD) Philip Ord Isaac Lalich

  2. A patient with Duchenne muscular dystrophy.

  3. Introduction • Characteristics • Weakness • Swollen Calve Muscles • Strange Gait • Muscle Wasting • Loss of Ambulation • Respiratory Insufficiency • Scoliosis • Cardiomyopathy (Some Cases) • 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

  4. Genetic information • 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

  5. Molecular description • Structural Protein • Links Actin to the Extra-Cellular Matrix • Gives Cell Rigidity • Cell is Destroyed with Muscle Contraction • Muscle Cells Stop Regenerating

  6. Brief history • (1836) • Meryon (1852) • GuillameDuchenne (1868) • DMD is a severe disease, patients pass in their late 20s to early 30s. • However medical science is making leaps and bounds.

  7. Clinical consequences • 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. Retrieved from: http://www.thesundaytimes.co.uk/sto/news/uk_news/Health/article646534.ece

  8. Treatment • Corticosteroid Therapy • Prednisone • Deflazacourt • Side Effects Severe • Weight Gain • Cushinoid Appearance • Emotional Issues • Delayed Puberty • Stunted Growth • Cataracts • Osteoporosis

  9. RESEARCH • 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. • 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.

  10. RESEARCH

  11. References • Bianchi, M., Biggar, D., Bushby, K., Rogol, A., Rutter, M., & Tseng, B. (2011). Endocrine aspects of Duchenne muscular dystrophy. Neuromuscular Disorders: NMD, 21(4), 298-303. • 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), 761-767. • Fairclough, R., Bareja, A., & Davies, K. (2011). Progress in therapy for Duchenne muscular dystrophy. Experimental Physiology, 96(11), 1101-1113. • Guglieri, M., & Bushby, K. (2010). Molecular treatments in Duchenne muscular dystrophy. Current Opinion In Pharmacology, 10(3), 331-337. • Hoffman, E., Brown, R., & Kunkel, L. (1987). Dystrophin: the protein product of the Duchennemuscular dystrophy locus. Cell, 51(6), 919-928. • 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), 1309-1316. • 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), 1059-1071. • Sussman, M. (2002). Duchenne muscular dystrophy. The Journal Of The American Academy Of OrthopaedicSurgeons, 10(2), 138-151.

More Related