Duchenne Muscular Dystrophy BRIAN CHANDA CHILUBA Dip PT

Duchenne Muscular Dystrophy BRIAN CHANDA CHILUBA Dip. PT; Cert. NDT NEUROLOGY CLASS PRESENTATION

Overview Basic information about Duchenne muscular dystrophy n Inheritance n Prevalence n Symptoms n Treatments n

What Is Duchenne Muscular Dystrophy? (1) n Genetic n Progressive muscle weakness n Defects in muscle proteins n Death of muscle tissue

MUSCULAR DYSTROPHY ØMuscular dystrophies - group of genetic conditions characterized by progressive muscle weakness and wasting (atrophy) Ø 20 different types of muscular dystrophy exist Ø(DMD) is named after the French neurologist Guillaume Benjamin Amand Duchenne (1806– 1875), who first described the disease in 1861

DMD Ø(DMD) is a severe recessive X-linked form of muscular dystrophy characterized by rapid progression of muscle degeneration, eventually leading to loss of ambulation and death ØDMD is caused by a defective gene for dystrophin (a protein in the muscles) or by mutations in the dystrophin gene, which is located on the X chromosome

DMD ØDMD absence of the dystrophin protein weakens the connections between all of the proteins in the muscle and the cell membrane Øcell membrane becomes weaker and ruptures Øparticles, such as calcium, can move in and out of the ruptured cell membrane

Where is This Gene?

PHYSIOLOGY OF DYSTROPHIN The dystrophin molecule anchors the cytoskeleton of muscle cells to the extracellular matrix, via the dystrophin glycoprotein complex. This includes the sarcoglycans (mutations in which cause limbgirdle muscular dystrophies) and dystroglycans. Muscle cells that lack dystrophin are mechanically fragile, and fail after a few years, hence progressive muscle weakness.

Duchenne Muscular Dystrophy Inheritance(1) n Mother carries the recessive gene and passes it to her child n Trait is usually expressed in males only

Prevalence of DMD(1) n Affects one in 3500 to 5000 newborn males n 1/3 of these with previous family history n 2/3 sporadic

Symptoms of DMD(1) Symptoms usually appear before age 6 n Delayed developmental milestones n n Loss of motor skills n Characteristic gait n Calf hypertrophy n Clumsiness/frequent falls

More Symptoms of DMD(1) n Muscle weakness n Difficulty climbing stairs or hills n Difficulty rising (Gower’s sign) n Difficulty walking/running

GOWERS SIGN

PROGNOSIS Duchenne muscular dystrophy leads to quickly worsening disability. Death usually occurs by age 25, typically from lung disorders

Treatments for DMD (1) n To improve breathing: n O 2 therapy n Ventilator n Scoliosis surgery n Tracheotomy

Treatments (cont. ) (1) n To improve mobility: n Physical therapy n Surgery on tight joints n Prednisone-ppppppppppp n Non-steroidal medications-oooooo n Wheelchair

PHYSIOTHERAPY TREATMENT AIM TO : Øminimize the development of contractures and deformity by developing a program of stretches and exercises where appropriate Øanticipate and minimize other secondary complications of a physical nature Ømonitor respiratory function and advise on techniques to assist with breathing exercises and methods of clearing secretions

The Beginning of Gene Therapy for DMD (2)

Advances in Gene Therapy(3) n Researches have developed "minigenes, " which carry instructions for a slightly smaller version of dystrophin, that can fit inside a virus n Researchers have also created the socalled gutted virus, a virus that has had its own genes removed so that it is carrying only the dystrophin gene

Problems with Gene Therapy(3) n Muscle tissue is large and relatively impenetrable n Viruses might provoke the immune system and cause the destruction of muscle fibers with the new genes

COMPLICATIONS • Cardiomyopathy • Congestive heart failure (rare) • Deformities • Heart arrhythmias (rare) • Mental impairment (varies, usually minimal) • Permanent, progressive disability Decreased mobility Decreased ability to care for self • Pneumonia or other respiratory infections • Respiratory failure

References: 1. “Muscular Dystrophy” Power. Point by Katherine Kolor, Ph. D, MS, CDC Ambassador Program, June 2005. 2. Pobojewski, S. The University Record, November 9, 1998. U-M’s improved viral vector delivers dystrophin gene to mouse muscle without major immune Response [online]. 1998. [cited 2005 June 26]. Available at URL: http: //www. umihc. edu/~urecord/9899/Nov 09_98/12. html 3. Journey of Love: A Parent’s Guide to Duchenne Muscular Dystrophy [online]. 2004. [cited 2005 June 22]. Available from URL: http: //www. mdausa. org/publications/journey/5. html 4. Dictionary. com. Lexico Publishing Group, LLC. [online]. 2005. [cited 2005 June 22]. Available from URL: http: //dictionary. reference. com/