Duchenne Muscular Dystrophy

(DMD)
Instructor:
Muhammad Imran Shabbir, PhD
Lecture 2
What Is Duchenne Muscular Dystrophy?

Genetic
Progressive muscle weakness
Defects in muscle proteins
Death of muscle tissue

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular

dystrophy, affecting around 1 in 3,600 boys, which results in muscle degeneration
and eventual death.

The disorder is caused by a mutation in the dystrophin gene, the largest gene
located on the human X chromosome, which codes for the protein dystrophin, an
important structural component within muscle tissue that provides structural
stability to the dystroglycan complex (DGC) of the cell membrane.

While both sexes can carry the mutation, females rarely exhibit signs of the
disease.
Where is This Gene?
Duchenne Muscular Dystrophy Inheritance

X-Linked Recessive
Mother carries the recessive gene and passes it
to her child
Trait is usually expressed in males only



Affects one in 3500 to 5000 newborn males
1/3 of these with previous family history
2/3 sporadic




Prevalence of DMD

X-linked Recessive Pattern
X-Linked Recessive Pattern
The X chromosome carrying the disease-causing mutation can be tracked through the family. Note: Shaded
squares = affected males: dots in circles = carrier females.
Exemplary DMD Pedigree
Symptoms of DMD

Delayed developmental milestones
Loss of motor skills
Characteristic gait
Calf hypertrophy
Clumsiness/frequent falls
Muscle weakness
Difficulty climbing stairs or hills
Difficulty rising (Gowers sign)
Difficulty walking/running



Muscles that are affected.
In the early stages,
Duchenne MD affect the
pectoral muscles (which
draw back the shoulders),
the trunk, and the upper
and lower legs. These
weaknesses lead to
difficulty in rising,
climbing stairs and
maintaining balance.
Muscle Fibers
Muscles are made of bundles
of fiber (cells). A group of
independent proteins along the
membrane surrounding each
fiber helps to keep muscle cells
working properly.
When one of these proteins,
dystrophin, is absent the result
is Duchenne MD; poor or
inadequate dystrophin results
in Becker MD.
Treatments for DMD

To improve breathing:
O
2
therapy

Ventilator

Scoliosis surgery

Tracheotomy

Treatments (cont.)

To improve mobility:
Physical therapy

Surgery on tight joints

Prednisone

Non-steroidal medications

Wheelchair


The Beginning of Gene Therapy
for DMD

Advances in Gene Therapy

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

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



Problems with Gene Therapy


Muscle tissue is large and relatively
impenetrable

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