New ALS Genetics Research Study Underway at Emory University; ALS
Center at Emory Offers Expertise to Patients Across Southeast
ATLANTA - It is one of the most devastating disorders affecting the
function of nerves and muscles in the body, according to the ALS Association.
Amyotrophic lateral sclerosis (ALS) -- often referred to as Lou Gehrigís
disease -- slowly and progressively robs patients of muscle control
and movement throughout the body. In the latter stages of the disease,
muscles often become totally paralyzed. While cognitive function usually
remains untouched, patients with ALS watch as their body withers away
while their thinking is still clear ≠ meaning these patients are aware
of the disease that will eventually lead to their death.
Researchers are not sure what causes ALS or why some people are affected
with more acute and more rapidly progressive symptoms than others. Now,
through a collaboration with an Icelandic genomics company called deCODE
genetics, Emory researchers are looking into the genetics of ALS for
these answers and others.
"During a five year project, Emory and several other sites hope to collect
blood samples from 500 ALS patients and their parents," says Jonathan
D. Glass, MD, professor of neurology at Emory University School of Medicine
and director of the ALS Center at Emory University. "Using thousands
of DNA markers developed by deCODE, the research team will be able to
identify genetic sequences throughout the human genome. With these markers,
the researchers will develop a DNA Ďfingerprintí of ALS patients and
their parents to determine whether inherited genes add susceptibility
of developing ALS."
Only about 10 percent of ALS cases are inherited directly from the parents.
Mutations in the superoxide dismutase (SOD1) or alsin (ALS2) gene in
some unknown way cause the decline and death of motor neurons, which
leads to muscle weakness and atrophy. Not all inherited cases, however,
can be attributed to SOD1 or ALS2 mutations, and mutations in other
as yet unidentified genes account for a large proportion of inherited
ALS. Ninety percent of cases, however, are assumed to be "sporadic",
meaning that the disease is not inherited. The Emory investigators are
searching this sporadic population for genetic factors that may not
directly cause ALS, but increase the risk of ALS in people carrying
Emory formed a strategic alliance with deCODE genetics in August 2002.
The company, based in Reykjavik, Iceland, uses its uniquely comprehensive
population data to uncover the genetic factors underlying common diseases.
The study of genealogy is a national Icelandic pastime, and family lineages
are well characterized and recorded. Because of this precise charting,
deCODE has created an extensive database that anonymously cross-references
genealogical information about the Icelandic population with genetic
and disease data from volunteer patients and their relatives in more
than 50 disease projects, including stroke, diabetes, breast and prostate
cancers, and Parkinsonís disease.
Armed with these important genetic clues from the Icelandic population,
Emory scientists are conducting their own research studies within Emoryís
diverse group of patients to uncover the full range of mutations or
versions of these genes that might predispose individuals to disease.
Although there are no ALS patients in Iceland to cross-reference with
samples being collected by Emory, the Emory researchers will use deCODEís
screening tools and methods during the five-year project. They believe
working towards identifying the genetic sequences of the disease, with
the help of deCODE, will prove to be beneficial.
At the ALS Center at Emory University, Dr. Glass and his colleagues
care for a patient base of about 100 to 130 people from all over the
Southeast. Supported by the Muscular Dystrophy Association (MDA) and
the ALS Association, the ALS Center at Emory University is the only
one of its kind in Georgia. Respiratory and physical therapists, nutritionists
and social workers care for the patients during their visits to the
center. Since there is no cure for ALS, Dr. Glass treats patients for
their symptoms, while continuing to research for causes and potential
treatments for their disease.
"The research in our laboratory focuses on finding pieces of ALS that
fit our other models of neurodegenerative disease and using common mechanisms
to treat them," says Dr. Glass. "We are looking at ways to delay the
death of motor neurons and prevent axon degeneration. For the past 15
years, we have been studying peripheral neuropathy and the death of
motor and sensory axons. Peripheral neuropathy is a neurological disorder
that causes weakness, numbness, burning, tingling and pain in the arms,
hands, legs and/or feet. We have good models of various agents that
can protect against peripheral neuropathy. Our mission is to look at
these same agents to see if they can prevent axon degeneration in motor
ALS affects the upper and lower motor neurons -- causing weakness, stiffness
and twitching in the limbs and trunk. The nerve cells in the brain and
the spinal cord are also under attack. The motor neurons in ALS progressively
deteriorate, waste away and then die, causing the brain to no longer
initiate and control muscle movement. As the disease advances to the
latter stages, patients can become totally paralyzed. Most ALS patients
die when the muscles that help them breathe are paralyzed. ALS is usually
fatal within five years after diagnosis. Fifty percent of patients die
within three years of onset.
Dr. Glass also treats patients with a similar motor neuron disease called
primary lateral sclerosis (PLS). PLS progresses much slower than ALS
and is typically not fatal. In PLS, only the upper motor neurons are
affected -- meaning that patients experience progressive muscle stiffness
and slowness in their voluntary muscles, but they donít develop degeneration
of spinal motor neurons, muscle wasting or muscle contractions, as in
ALS. Because of its slow course, patients with PLS may live up to 20
years after diagnosis. As many as 30,000 Americans have ALS. The population
of PLS is much less -- approximately 400.
As for the genetics study at Emory, ALS patients and their parents are
now being recruited. Since most ALS patients donít develop the disorder
until they are in their 40s to 70s, the task of finding 500 patients
with living parents will be daunting. For more information about this
ALS genetic research study, please call 888-413-9315.