duchenne muscular dystrophy (dmd)
DESCRIPTION
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 ). - PowerPoint PPT PresentationTRANSCRIPT
Philip OrdIsaac 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
Insuffi ciency Scoliosis Cardiomyopathy (Some
Cases)
INTRODUCTION
Dystrophin GeneLocus: Xp21X-Linked RecessiveMutation Types
Point Mutation Frameshift Massive Missense
Premature Stop Codon (Nonsense)
Large Deletion Location of Mutation
Correlates with SeverityExtremely Large Gene
24 KB 3,685 AA
GENETIC INFORMATION
Structural ProteinLinks Actin to the
Extra-Cellular Matrix
Gives Cell RigidityCell 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 insuffi ciency:
eventual need for ventilator. Prone to respiratory infection.
CLINICAL CONSEQUENCES
Retrieved from: http://www.thesundaytimes.co.uk/sto/news/uk_news/Health/article646534.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
diffi cult. 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
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), 298-303.
Bianchi , M., Mazzanti , A. , Galbiat i , E. , Saraifoger, S. , Dubini , A. , Cornel io, F. , & Morandi , L . (2003). Bone mineral density and bone metabol ism in Duchenne muscular dystrophy. Osteoporosis Internat ional , 14 (9), 761-767.
Fairc lough, R., Bareja, A., & Davies, K. (2011). Progress in therapy for Duchenne muscular dystrophy. Experimental Physiology , 96 (11), 1101-1113.
Gugl ier i , M., & Bushby, K. (2010). Molecular treatments in Duchenne muscular dystrophy. Current Opinion In Pharmacology , 10 (3), 331-337.
Hoff man, E., Brown, R., & Kunkel , L . (1987). Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cel l , 51 (6), 919-928.
Pradhan, S. , Ghosh, D., Sr ivastava, N., Kumar, A., Mittal , B., Pandey, C., & Singh, U. (2006). Prednisolone in Duchenne muscular dystrophy with imminent loss of ambulat ion. Journal Of Neurology , 253 (10), 1309-1316.
Sacco, A., Mourkiot i , F. , Tran, R., Choi , J . , L lewel lyn, M., Kraft , P. , Shkrel i , M., Delp, S., Pomerantz, J . , Artandi , S. , & Blau, M. (2010). Short teleomeres and stem cel l exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cel l , 147 (7), 1059-1071.
Sussman, M. (2002). Duchenne muscular dystrophy. The Journal Of The American Academy Of Orthopaedic Surgeons , 10 (2), 138-151.
REFERENCES