It is one of the most devastating disorders affecting
the function of nerves and muscles in the body. Amyotrophic lateral
sclerosis (ALS)—often referred to as Lou Gehrig’s disease—slowly
and progressively robs patients of muscle control and movement throughout
In the latter stages of the disease, muscles often become totally
paralyzed, and 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 the Icelandic genomics
company deCODE genetics, Emory researchers are looking into the
genetics of ALS for these and other answers.
"During a five-year project, Emory and several other sites
hope to collect blood samples from 500 ALS patients and their parents,"
said Jonathan Glass, professor of neurology in the School of Medicine
and director of Emory’s ALS Center. "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 ‘fingerprint’
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
are assumed to be "sporadic," meaning that the disease
is not inherited. Emory investigators are searching this sporadic
population for genetic factors that may not directly cause ALS but
increase the risk in people carrying these genes.
Emory formed a strategic alliance with deCODE in August 2002. The
company, based in Reykjavik, uses its uniquely comprehensive population
data to uncover the genetic factors underlying common diseases.
The study of genealogy is an 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 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 Parkinson’s
Armed with these important genetic clues, University scientists
are conducting their own research studies within Emory’s diverse
patient population to uncover the full range of mutations or genetic
variations that might predispose individuals to disease. Although
there are no ALS patients in Iceland to cross-reference with samples
being collected in Atlanta, the Emory researchers will use deCODE’s
screening tools and methods. They believe working toward identifying
the genetic sequences of the disease will prove beneficial.
At the ALS Center, Glass and his colleagues care for a patient base
of 100–130 people from across the Southeast. Supported by
the Muscular Dystrophy Association and the ALS Association, the
center 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,
Glass treats patients for their symptoms while continuing to research
causes and novel treatments.
"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," Glass said. "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," he continued. "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 neuron disease."
ALS patients and their parents are now being recruited for the genetics
study. Since most ALS patients don’t develop the disorder
until their 40s, the task of finding 500 patients with living parents
will be daunting. For more information, call 1-888-413-9315.