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