DuchenneDuchenneMuscular Muscular DystrophyDystrophyBRIAN CHANDA CHILUBABRIAN CHANDA CHILUBA

Dip.PT; Cert. NDTDip.PT; Cert. NDT

NEUROLOGY CLASS NEUROLOGY CLASS PRESENTATIONPRESENTATION

OverviewOverview

Basic information about Duchenne Basic information about Duchenne muscular dystrophymuscular dystrophy

InheritanceInheritance PrevalencePrevalence SymptomsSymptoms TreatmentsTreatments

What Is Duchenne What Is Duchenne Muscular Dystrophy?Muscular Dystrophy?(1)(1)

GeneticGenetic

Progressive muscle weaknessProgressive muscle weakness

Defects in muscle proteinsDefects in muscle proteins

Death of muscle tissueDeath of muscle tissue

MUSCULAR DYSTROPHYMUSCULAR DYSTROPHYMuscular dystrophies - group of genetic conditions

characterized by progressive muscle weakness and wasting

(atrophy)

20 different types of muscular dystrophy exist

(DMD) is named after the French neurologist Guillaume

Benjamin Amand Duchenne (1806–1875), who first described the

disease in 1861

DMDDMD

(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

DMD 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

DMDDMD

DMD absence of the dystrophin protein weakens the

connections between all of the proteins in the muscle and the cell

membrane

cell membrane becomes weaker and ruptures

particles, such as calcium, can move in and out of the ruptured

cell membrane

Where is This Gene?Where is This Gene?

PHYSIOLOGY OF PHYSIOLOGY OF DYSTROPHINDYSTROPHIN

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 limb-girdle muscular dystrophies) and dystroglycans.

Muscle cells that lack dystrophin are mechanically fragile, and fail after a few years, hence progressive muscle weakness.

Duchenne Duchenne Muscular Muscular Dystrophy InheritanceDystrophy Inheritance(1)(1)

Mother carries the recessive gene Mother carries the recessive gene and passes it to her childand passes it to her child

TraitTrait is usually expressed in is usually expressed in

males onlymales only

Prevalence of DMDPrevalence of DMD(1)(1)

Affects one in Affects one in 3500 to 5000 3500 to 5000 newborn malesnewborn males

1/3 of these 1/3 of these with previous family previous family historyhistory

2/3 sporadic2/3 sporadic

Symptoms of DMDSymptoms of DMD(1)(1)

Symptoms usually appear before age 6 Symptoms usually appear before age 6 Delayed developmental milestonesDelayed developmental milestones

Loss of motor skillsLoss of motor skills

Characteristic gaitCharacteristic gait

Calf hypertrophyCalf hypertrophy

Clumsiness/frequent fallsClumsiness/frequent falls

More Symptoms of More Symptoms of DMDDMD(1)(1)

Muscle weaknessMuscle weakness

Difficulty climbing stairs or hillsDifficulty climbing stairs or hills

Difficulty rising (Gower’s sign)Difficulty rising (Gower’s sign)

Difficulty walking/runningDifficulty walking/running

GOWERS SIGNGOWERS SIGN

PROGNOSISPROGNOSIS

Duchenne muscular dystrophy leads to

quickly worsening disability. Death

usually occurs by age 25, typically from

lung disorders

Treatments for DMD Treatments for DMD (1)(1)

To improve breathing:To improve breathing: OO22 therapy therapy

VentilatorVentilator

Scoliosis surgeryScoliosis surgery

TracheotomyTracheotomy

Treatments (cont.) Treatments (cont.) (1)

To improve mobility:To improve mobility: Physical therapyPhysical therapy

Surgery on tight jointsSurgery on tight joints

Prednisone-pPrednisone-ppppppppppppppppppppppppppppppppppppppppp

Non-steroidal medications-Non-steroidal medications-oooooooooooo

WheelchairWheelchair

PHYSIOTHERAPY PHYSIOTHERAPY TREATMENTTREATMENT

AIM TO :

minimize the development of contractures and deformity by developing a program of stretches and exercises where appropriate

anticipate and minimize other secondary complications of a physical nature

monitor 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 Advances in Gene TherapyTherapy(3)(3)

Researches have developed Researches have developed ""minigenes,minigenes," which carry instructions " which carry instructions for a slightly smaller version of for a slightly smaller version of dystrophin, that can fit inside a virusdystrophin, that can fit inside a virus

Researchers have also created the so-Researchers have also created the so-called called gutted virus,gutted virus, a virus that has had a virus that has had its own genes removed so that it is its own genes removed so that it is carrying only the dystrophin gene carrying only the dystrophin gene

Problems with Gene Problems with Gene TherapyTherapy(3)(3)

Muscle tissue is large and relatively Muscle tissue is large and relatively impenetrableimpenetrable

Viruses might provoke the immune Viruses might provoke the immune system and cause the destruction of system and cause the destruction of muscle fibers with the new genes muscle fibers with the new genes

COMPLICATIONSCOMPLICATIONS•Cardiomyopathy•Congestive heart failure (rare)•Deformities•Heart arrhythmias (rare)•Mental impairment (varies, usually minimal)•Permanent, progressive disability

Decreased mobilityDecreased ability to care for self

•Pneumonia or other respiratory infections•Respiratory failure

References:References:1. “Muscular Dystrophy” PowerPoint by Katherine Kolor, PhD, 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/Nov09_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/