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May 11, 2007
AAN Meeting Report
Here
is a summary of news about amyotrophic
lateral sclerosis (ALS, or Lou Gehrig’s
disease) reported at the American
Academy of Neurology 59th Annual
Meeting, April 28-May 4 in Boston.
Many of the findings
resulted from MDA research funding
and/or the contributions of MDA
clinic physicians.
MINOCYCLINE
INEFFECTIVE FOR ALS
Disappointing results
of a nine-month trial of the drug
minocycline were announced.
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 attended 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
MORE ALS FINDINGS
-
Variations
in a gene for a protein called
progranulin can modify the course
of ALS according to a study of
230 people with ALS and 436 without
the disease in Belgium. This finding
could have implications for understanding
and treatment of ALS.
-
Administering
a compound called SOD1 antisense
directly into the brains of rats
destined to develop a genetic
form of ALS slowed the progression
of the disease early in its course
and extended survival. If the
drug was given prior to the onset
of the disease, the increase in
survival was 30 days; but if treatment
was started close to disease onset,
survival increased by 10 days.
SOD1 antisense blocks genetic
instructions for the SOD1 protein.
In this form of ALS, these instructions
are abnormal and lead to production
of a highly toxic, disease-causing
protein. Plans to test this treatment
in people with SOD1-caused ALS
are under way.
-
An
analysis of muscle tissue in 33
people with 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.
-
In
a second study about Nogo_A, researchers
reported that detection of this
protein in muscle tissue may be
a way to identify ALS very early
in the course of the disease,
when the diagnosis is still uncertain.
Further studies are necessary
to determine whether Nogo-A may
be a potential biomarker for ALS.
-
A
comparison of the DNA in all genes
of 276 Americans and 277 Italians
with ALS and 2,130 Americans and
Italians without the disease has
been completed. Two genetic variants
that may increase the risk for
developing sporadic ALS were identified
in the Italian cohort but not
in the US cohort of individuals
with ALS. These results may yield
new clues for understanding the
causes of and biochemical pathways
involved in sporadic ALS.
-
Variations
in the genes for two enzymes,
known as PON1 and PON3, appear
to be risk factors for ALS, according
to a study of 221 Irish ALS patients
and 202 healthy subject of similar
age, gender and ethnic background.
These PON genes, which have previously
been implicated in other ALS studies,
are involved in detoxification
of pesticides and other chemical
compounds.
-
A
study of 65 people with ALS and
their primary caregivers (who
were separately interviewed) found
that the diagnostic phase of ALS
is a time of moderate to high
anxiety levels for patients, but
that these tend to decrease as
the disease progresses. Anxiety
in caregivers, however, did not
decrease with disease progression.
-
Mutations
in a gene for the SOD1 protein,
known to cause a type of familial
ALS, don’t do so by damaging
muscle tissue, a new study shows.
Increasing muscle mass and strength
did not slow the onset or progression
of ALS in mice with the SOD1 form
of the disease, although enhanced
muscle mass led to temporary strength
gains.
-
Phrenic
nerve conduction studies are a
useful tool in evaluating whether
the respiratory status of paralyzed
patients will benefit from implantation
of electrodes that stimulate the
diaphragm. The phrenic nerve normally
controls diaphragm movement. This
type of “diaphragm pacemaker
implantation” strategy is
being tested in people with spinal
cord injuries and ALS.
-
Mice
with a genetic form of ALS because
of a mutation in the gene for
the SOD1 protein responded well
to a compound called anti-SOD1
siRNA, designed to block erroneous
SOD1 genetic instructions. Mice
bred to produce this anti-SOD1
compound and also bred to have
an SOD1 mutation didn’t
develop ALS symptoms until they
were 280 days old, whereas all
the animals with an SOD1 mutation
without it died by 160 days.
-
A
20-week trial of sodium phenylbutyrate
in 40 people with 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.
-
Cells
called microglia taken from the
nervous systems of mice with 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.
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