February
2, 2006
International
ALS Meeting Covers
Research, Care and Goals
Dr. Valerie Cwik,
MDA’s medical director and
a neurologist who formerly directed
the MDA/ALS Center in Tucson,
Ariz., attended the 16th International
Symposium on ALS/MND in Dublin,
Ireland, in December.
The meeting was
sponsored by the British Motor
Neurone Disease Association, in
cooperation with the International
Alliance of ALS/MND Associations.
This year’s conference was
attended by some 900 neurologists,
basic scientists and allied health
professionals.
Here’s Dr.
Cwik’s report.
Clinical
Trials Results
Results of several
clinical trials were presented.
A summary follows.
- AEOL 10150, a potent
antioxidant made by Aeolus
Pharmaceuticals that targets
dangerous byproducts of cellular
metabolism, was reported to
be safe and well tolerated
by ALS patients at a variety
of dosage levels. Robert Miller,
director of the MDA/ALS Center
in San Francisco, reported
the results and said a larger
trial is planned.
- Glatiramer acetate (Copaxone),
a drug used in the treatment
of multiple sclerosis that
may boost production of cells
that suppress the immune system,
was reported to be safe and
well tolerated in ALS patients
in a clinical trial involving
some 30 participants. Paul
Gordon, co-director of the
MDA/ALS Center at Columbia
University in New York, announced
the results. Further studies
are planned.
- TCH346, a small
molecule developed by Novartis,
designed to block the cell
death pathway, failed to demonstrate
a beneficial effect on disease
progression. The trial included
some 500 ALS patients, divided
into groups taking four different
dosage levels of TCH346 and
a placebo (inert substance)
group.
- A nine-month study of creatine
in some 100 ALS patients also
failed to show benefit, confirming
the negative findings of two
previous creatine studies
in ALS. The trial was coordinated
by Jeffrey Rosenfeld, director
of the MDA/ALS Center in Charlotte,
N.C.
Clinical Trial Design
Several presentations
focused on the design and conduct
of clinical trials in ALS. Clinical
trials in this disease typically
require large number of patients,
a relatively long duration, and
are expensive. New designs to
address these issues were discussed.
Briefly, these included
- so-called inferiority/superiority
study designs to rapidly
screen therapies in relatively
small numbers of patients
and either exclude a treatment
from further testing or recommend
it for a larger study
- studies using patients with
rapidly progressing ALS
- studies that compare the
rate of progression of a patient’s
disease before and after an
experimental treatment
instead of comparing a treated
group of patients to an untreated
(control) group
Studies in ALS Genetics
and Epidemiology (Disease Patterns)
A number of speakers
addressed genetic and epidemiologic
issues in ALS.
- Christen Shoesmith, an MDA
grantee at the University
of Western Ontario, presented
the results of a study showing
that about 2 percent of ALS
patients have respiratory
impairment as their first
disease symptom, that
this pattern is more common
in males, and that it does
not necessarily mean the disease
will progress faster.
- There appears to be a reduced
incidence of ALS among
African-Americans and among
immigrants to the United Kingdom
from the Indian subcontinent,
the Caribbean and Africa compared
to other ethnic groups.
- Smoking did not
appear to be a risk factor
for ALS in a study from Australia.
- Genetic susceptibility
to certain viruses or toxins
may underlie some cases of
ALS.
- Hiroshi Mitsumoto, who co-directs
the MDA/ALS Center at Columbia
University in New York, presented
results of his MDA-funded
work to develop a structured
interview on which to base
a study of potential genetic
and environmental risk factors
for ALS. Some items in the
interview questionnaire have
been revised from their original
form. Telephone interviews
appear to be as reliable as
face-to-face interviews, simplifying
the research process.
Current Treatments
Some sessions focused
on currently available treatments.
Among these were presentations
on
- advances in gastrostomy
(feeding) tube placement and
care, including 1) a
new mask that allows for simultaneous
noninvasive ventilation and
g-tube placement, reducing
the risk of respiratory complications
during tube insertion and
2) a method of placing gastrostomy
tubes without sedation and
with only local anesthesia,
reducing risks for the ALS
patient
- approaches to respiratory
care, including 1) increasing
lung capacity through breath
stacking 2) the use of
manually or mechanically assisted
coughing to handle mucus
buildup and 3) the use of
a vibrating vest
to assist in getting rid of
mucus buildup, a technique
that was met with skepticism
by the conferees
Caring for Caregivers
Several presentations
highlighted the need to attend
to the needs of caregivers of
ALS patients, as well as the patients
themselves. When the patient is
cognitively impaired, the negative
impact on the caregiver is greater,
the presenters said.
Basic Science Research
Several studies
in cells and animal models of
ALS were presented. A summary
of findings follows.
- A newly identified compound
called angiogenin,
which is produced in the nervous
system, was found to protect
nerve cells (neurons) in laboratory
dishes from certain types
of injury.
- In mice with an ALS-causing
mutation in a gene known as
SOD1, a combination of exercise
and insulin-like growth factor
1 (IGF1) nearly doubled
survival time.
- Compounds called antisense
oligonucleotides can
reduce levels of abnormal
SOD1 protein in rats with
an ALS-causing mutation in
the SOD1 gene. Treatment with
these compounds did not delay
the onset of ALS, but it did
modestly extend survival.
Further studies are under
way to develop antisense therapy
as a possible treatment for
familial ALS related to the
SOD1 gene.
Recognition of MDA Grantee
Stanley Appel,
a long-time MDA research grantee
and director of the MDA/ALS Center
at Methodist Hospital in Houston,
was given the Forbes Norris
Award for exceptional care
and compassion in the study and
management of ALS. Appel’s
current work focuses on the role
of the immune system and inflammatory
processes in ALS.
Toward the Future
At a meeting of
the ALS Research Group,
formed at an MDA-sponsored conference
on ALS held in 2003 in Tarrytown,
N.Y., an ALS DNA banking project,
to be funded mostly by the National
Institutes of Health, was discussed.
The researchers hope to store
DNA from some 2,000 blood samples
taken from people with and without
ALS.
At the inaugural
meeting of MDA’s new ALS
Translational Research Advisory
Committee (TRAC), Stan Appel,
meeting chairman, encouraged discussion
of the committee’s goals.
Like MDA’s general TRAC,
the ALS TRAC will help promising
research move from the laboratory
to clinical trials in as
short a time as possible. Sharon
Hesterlee, MDA’s research
development director, will work
with him to plan the next steps.
