MDF Newsletter Content Issue 46 April 2015

Research
The study was based on previous results
in animal models of Duchenne
muscular dystrophy showing that
eplerenone, when used in combination
with other heart drugs, can reduce heart
muscle damage. However, further studies
are needed to understand the effects
of combination therapy to protect the
heart muscle.
In this new clinical trial, Raman and her
colleagues tested the effect of eplerenone
in combination with other heart
drugs on 42 individuals with Duchenne
muscular dystrophy that showed early
heart muscle damage. Each participant
was given either eplerenone or a placebo
once a day for a year, while also
taking heart medicine prescribed by
their physician. The trial was done in
a double blind way meaning that neither
the patients nor the clinicians knew
who was receiving the drug and who
was receiving the placebo.
After 12 months of taking the drug the
decline in heart function was significantly
reduced in participants who received
eplerenone compared to those
who received a placebo. The findings
of Dr Raman show that early use of
eplerenone could slow heart function
decline in people affected by Duchenne
muscular dystrophy.
In the future, a combination therapy
that includes eplerenone to prevent
heart muscle damage could be used as
standard in people affected by Duchenne
muscular dystrophy according to
Dr Linda Cripe, a co-researcher and pediatric
cardiologist at Nationwide Children’s
Hospital in Columbus.
Duchenne muscular dystrophy is a very
serious muscle wasting condition. The
first signs of the condition are difficulty
in walking, running jumping and climbing
stairs. As the condition progresses
the muscles involved in breathing and
the heart muscle are also affected.
Most patients develop respiratory and
heart failure in their 20s or early 30s.
Drugs treating complication associated
with breathing have improved life expectancy.
However deterioration of the
heart muscle remains the leading cause
of death.
Dr Marita Pohlschmidt, Director of
Research at the Muscular Dystrophy
Campaign said:
Heart failure is one of the major concerns
for people affected by Duchenne
muscular dystrophy. A lot of
therapeutic approaches address the
weakness of the skeletal muscle and
heart failure comes second. We particularly
welcome this study as it
addresses one of the major issues in
Duchenne muscular dystrophy. We
look forward to the results of further
clinical tests aimed at confirming
these initial findings.
Article online at http://www.musculardystrophy.org/research/news/8177
New clinical trial for SMA drug
Friday 30 January 2015
A new clinical trial for people with spinal
muscular atrophy (SMA) types 2
and 3 is now recruiting participants in
London and Newcastle. The aim of the
trial is to test the effectiveness of a new
oral drug in increasing the production
of the SMN protein.
SMN or survival motor neuron protein
is essential for the survival of motor
neurons, the nerves that control the
movement of the muscles.
We have two genes that make SMN
protein: SMN1 and SMN2. The protein
is mainly made from the SMN1 gene
while the SMN2 gene only produces
about 10% of functional protein.
People affected by SMA carry a mutation
in the SMN1 gene and no protein
is produced from this gene. The small
amount of functional SMN protein
produced from the SMN2 gene is not
enough for the nerve cells to function
properly. This leads to muscle wasting.
The drug RO6885247 has been tested
on animal models of SMA and it was
found that it significantly increases the
production of functional SMN protein
from the SMN2 gene. It was also found
that the drug improves the function of
the nerve cells and extends the life span
of the animals.
The drug was developed as a collaboration
between PTC, Roche and the SMA
foundation. The current trial is sponsored
by Hoffmann-La Roche.
The drug is now in phase I clinical trial.
In the UK there are two sites, one in
London and one in Newcastle recruiting
both male and female participants
aged 16 to 55. At a later stage the trial
will be extended to include participants
from two years of age. The trial is also
taking place in Italy, the Netherlands,
Switzerland and the United States.
To be considered for the trial, individuals
must have a confirmed genetic diagnosis
of SMA types 2 or 3. Individuals
who have participated in other clinical
trials in the past, have undergone surgery
for scoliosis in the last six months
or have kidney, liver or heart problems
may not be eligible.
Individuals will receive the drug for a
period of 12 weeks. The trial will be
placebo controlled and be conducted in
a double blind way meaning that neither
the participants nor the clinicians
will know who is receiving the placebo
and who is receiving the drug.
The effect of the drug on the production
of functional SMN protein will be
tested. A number of blood and muscle
function tests will also be performed to
test the safety and effectiveness of the
drug.
Dr Marita Pohlschmidt, Director of
Research at the Muscular Dystrophy
Campaign said:
We are encouraged to see that a new
drug that has the potential to help
people affected by spinal muscular
atrophy is being tested in clinical trials.
We have funded research into SMA
for many years. We look forward to
the results of this phase I trial.
Article online at http://www.musculardystrophy.org/research/news/8117
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