| Research |
|
|
|
|
|
|
|
|
 |
Enter your zip code
|
|
|
|
|
|
|
May
1, 2007
MINOCYCLINE INEFFECTIVE
FOR ALS;
NEWS FROM AAN ANNUAL MEETING
Disappointing
results of a nine-month trial of
the drug minocycline for amyotrophic
lateral sclerosis (ALS or Lou Gehrig’s
disease) were announced today at
the American Academy of Neurology
Annual Meeting in Boston.
Minocycline
demonstrated no beneficial effect,
and for some patients, worsened
measurable outcomes.
People
with ALS who are currently taking
the drug, an antibiotic in the tetracycline
family, are urged to contact their
physician to discuss discontinuing
its use, said MDA Medical Director
Valerie Cwik, who is at the meeting.
The
drug did not affect survival or
quality of life measures for people
with ALS in the trial.
The
trial tested minocycline versus
a placebo (inert, look-alike substance)
in 412 people at 31 U.S. centers.
The drug was thought to reduce inflammation
and counteract cell death.
ADDITIONAL
HIGHLIGHTS FROM THE AAN ANNUAL MEETING
(April 28-May 5, Boston)
DUCHENNE
AND BECKER MD
-
An analysis of a large database
of patients with Duchenne muscular
dystrophy (DMD) or Becker muscular
dystrophy (BMD) reveals that severity
of the disease cannot always be
predicted from analysis of the
genetic mutation. About 10 percent
of the time, mutations that predict
the more severe DMD actually turn
out to be the less severe BMD.
-
Delivering therapeutic genes for
the muscle protein dystrophin
to a whole limb at a time, via
the bloodstream, to treat Duchenne
muscular dystrophy (DMD) or Becker
muscular dystrophy (BMD), is feasible,
suggest tests in a dystrophin-deficient
mouse and a larger animal. The
best delivery systems were viral
shells called AAV6 and AAV8.
-
A drug called idebenone, which
may increase cellular energy production,
improved heart function and exercise
performance in dystrophin-deficient
mice with a disease resembling
Duchenne muscular dystrophy (DMD).
AMYOTROPHIC
LATERAL SCLEROSIS (ALS)
-
A
20-week trial of sodium phenylbutyrate
in 40 people with amyotrophic
lateral sclerosis (ALS) at eight
centers showed the drug was safe
and tolerable for the majority
of participants at dosages between
12 and 21 grams per day.
-
An
analysis of muscle tissue in 33
people with amyotrophic lateral
sclerosis (ALS), ALS with dementia
or dementia alone, seven people
with various other neuromuscular
disorders, and 12 people without
a neuromuscular disorder showed
that a protein in muscle called
Nogo-A was found in 20 out of
23 (87 percent) of the ALS patients.
It was also found in five out
of five people with ALS and dementia
(100 percent) and three out of
five with dementia alone (60 percent).
None of the other 19 study participants,
who had another neuromuscular
disease or no neuromuscular disease,
had this protein in their muscle
tissue. The significance of these
results isn’t yet clear.
-
Rats
with amyotrophic lateral sclerosis
(ALS) caused by mutated SOD1 genes
were helped by a compound called
antisense that was designed to
keep cells from following the
erroneous genetic instructions
that would produce an abnormal
and toxic SOD1 protein. Onset
of symptoms wasn’t affected,
but early disease progression
was slowed, and survival was extended
by a month. The study supports
the use of this type of therapy
for SOD1-related ALS.
-
Cells
called microglia taken from the
nervous systems of mice with amyotrophic
lateral sclerosis (ALS) caused
by mutated SOD1 genes are more
toxic when active than are microglia
taken from healthy mice. Microglia
are the cells that carry out an
immune response in the nervous
system. The study supports the
hypothesis that activated microglia
play a role in ALS.
-
Using
antisense technology to change
the way muscle cells interpret
genetic information for the so-called
chloride channel protein was effective
in a mouse model of type 1 myotonic
dystrophy (MMD). The treatment
restored normal chloride channel
production and relieved myotonia
(prolonged muscle contractions)
in the mice.
-
An
18-year study of six people with
a genetic mutation in each of
their two PABPN1 genes found that
such patients develop very severe
oculopharyngeal muscular dystrophy
(OPMD), which normally results
from only one PABPN1 mutation.
All six developed drooping eyelids
and difficulty swallowing before
age 30. They later developed weak
eye movement muscles, trouble
speaking, limb weakness and cognitive
deficits. Five required feeding
tubes.
-
An
analysis of 50 children with the
rare early childhood form of facioscapulohumeral
muscular dystrophy (FSHD) confirmed
earlier reports that this form
of FSHD is more severe than adult
FSHD. The majority had facial
and other muscle weakness and
muscle pain. Other problems reported
more frequently in the infantile
form of FSH were hearing loss,
respiratory effects and requiring
a wheelchair by age 18.
-
Analysis
of 58 people with late-onset Pompe’s
disease (also known as acid maltase
deficiency or AMD) revealed slow
progression of limb and respiratory
muscle weakness over a year’s
time is probably typical. The
average respiratory muscle test
score dropped by 3.5 percent and
the average leg muscle test score
by 3.2 percent. The average age
of symptom onset was 29.
-
A
congenital myasthenic syndrome
(disturbance of nerve-to-muscle
signal transmission due to a genetic
mutation) that results from a
mutation in the gene for dok-7,
a protein found at the junction
of nerve and muscle, was described
in 13 patients. The investigators
said this type of myasthenia probably
involves ongoing destruction and
remodeling at the neuromuscular
junction.
-
Adding
the immune-system suppressant
mycophenolate mofetil (CellCept)
to prednisone, a standard immune-system
dampener, in patients with myasthenia
gravis (MG), failed to improve
strength, ability to perform daily
activities or biochemical measurements
of disease activity. MG is a disorder
in which the immune system mistakenly
attacks parts of the nerve-muscle
junction. Participants took either
prednisone at 20 milligrams per
day plus 2.5 grams per day of
CellCept, or prednisone plus a
placebo (look-alike inactive substance)
for three months.
-
When
the investigators examined the
records of 21 patients who were
treated for 24 episodes of myasthenic
crisis (myasthenia-related respiratory
failure) between 1987 and 2006,
they found that 14 (58 percent)
of the episodes were successfully
treated with noninvasive methods
alone. Noninvasive ventilation
support is pressurized air supplied
through a mask or oral or nasal
interface; invasive ventilation
support is pressurized air delivered
through a surgically created hole
in the trachea (tracheostomy).
-
Lambert-Eaton
syndrome (LES), a type of myasthenia
in which the immune system attacks
the part of the nerve fiber from
which signals are transmitted
to muscle, is sometimes found
in conjunction with small-cell
lung cancer; and when it is, it
appears to improve the cancer
survival rate. At five years after
diagnosis, 36 percent of patients
with this type of cancer and LES
were alive, which was significantly
greater than the survival rate
in the general small-cell lung
cancer population. (LES may reflect
the immune system’s efforts
to attack the cancer, with off-target
effects on the nerve-muscle junction.)
|
| |
|
| |
|
| |
|
|
|
|
