Duchenne muscular dystrophy, a
disease that develops in early
childhood and most often results in the
death by age 30. The disease strikes
only boys, about one in 3,500, and
affects more than 30,000 people in the
United States, Europe and Japan.
Duchenne is one of nine different
types of muscular dystrophy.(DMD)
Duchenne is a muscle wasting disease
and occurs when the protein
dystrophin is either missing or altered.
Dystrophin binds the outside of a
muscle cell membrane to the
cytoskeleton inside the membrane.
Dystrophin is a very difficult protein to
replace because it is enormous. It has
the biggest piece of DNA coding of any
protein known in the body.
ETEPLIRSEN (AVI-4658) IS A
PROMISING DRUG FOR MUSCULAR
Update in April 2012:
AVI BioPharma, Inc. a developer of
RNA-based therapeutics, announced
that treatment with eteplirsen met the
primary efficacy endpoint in a
randomized, double-blind, placebo-
controlled Phase IIb study in boys with
Duchenne muscular dystrophy (DMD).
Eteplirsen administered once weekly at
30mg/kg over 24 weeks resulted in a
statistically significant (p ≤ 0.002)
increase in novel dystrophin (22.5%
dystrophin-positive fibers as a
percentage of normal) compared to no
increase in the placebo group. .
"This study represents a major
advance in the field of DMD research
as the results indicate that eteplirsen is
producing consistent levels of
dystrophin, which is the essential
protein that these patients need," said
Jerry Mendell, director of the Centers
for Gene Therapy and Muscular
Dystrophy at Nationwide Children's
Hospital and principal investigator of
the study. "We anticipate that these
levels of dystrophin could lead to
significant clinical benefit if maintained
over a longer course of treatment."
A study published in July 2011 by The
Lancet in London shows it is possible,
using a targeted antisense therapy
called AVI-4658, to restore expression
of a key protein that is lacking in
patients with the seriously debilitating
condition Duchenne muscular
The Article is by Professor Francesco
Muntoni, Dubowitz Neuromuscular
Centre, London, UK, and colleagues.
The study was part funded by AVI
BioPharma, the maker of the drug.
In the UK around 1 in 3500 males
have Duchenne muscular dystrophy.
The condition causes progressive
muscle weakness due to the
breakdown and loss of muscle cells.
Patients are deficient in a single
important protein in muscle fibres
called dystrophin. By about 8 to 12
years of age boys become unable to
walk, and by their late teens or
twenties the condition is so serious it
often leads to an early death.
Antisense therapy has potential to
treat many, but not all, patients with
19 patients aged 5 to 15 years
received the study drug for 12 weeks
at either Great Ormond Street Hospital
for Children NHS Trust (GOSH),
London, UK, or the Royal Victoria
Infirmary, Newcastle, UK. Each boy had
a muscle biopsy before and after
The team found that use of AVI-4658
helped 'repair' the boys' ability to
produce a functional mRNA through
'exon skipping' and eventually allow
them to produce functional dystrophin
protein. The authors say: "Seven
patients had a significant dose
response, six of whom were in the two
high-dose cohorts, showing restoration
of dystrophin protein expression up to
18% of normal levels."
RITUXAN IMPROVES MUSCLE
STRENGTH IN MUSCULAR
Rituxan Improves Strength In Form Of
Muscular Dystrophy according to a
recent small study. Rituxan is made by
The blockbuster drug Rituxan appears
to fight a form of muscular dystrophy,
according to research published in
BMC Musculoskeletal Disorders.
Treatment with Rituxan resulted in
improved muscle strength in two
patients with dysferlin-deficient
muscular dystrophy, or a condition
related to polymyositis, according to
the article. This is the latest in a series
of indications Rituxan has shown
efficacy in treating.
Rituxan soared to fame in the late
1990s as the first approved
monoclonal antibody cancer
therapeutic. It was approved by the
FDA in 1997. Rituxan targets an
antigen called CD20 found on white
blood cells called B cells.
The findings are pertinent to treating
Miyoshi myopathy, a form of muscular
ACE031 TESTED FOR MUSCULAR
The experimental drug ACE031, which
is designed to interfere with the actions
of the naturally occurring protein
myostatin, is being tested in some 76
boys with Duchenne muscular
dystrophy (DMD) who are at least 4
In April 2010, Acceleron Pharma, of
Cambridge, Mass., announced the
drug shows promise as a therapy to
increase muscle mass, based on
results of a trial conducted in healthy
The study is being conducted in
London, Ontario, Canada
Justin Fallon at Brown University is
trying to find ways to increase a
dystrophin replacement called
utrophin, a protein similar to
dystrophin. Fetuses have utrophin
while developing in the womb, but
when a baby is born, the utrophin goes
down and the dystrophin goes up.
Fallon will be ready to start the clinical
trial process next year.