October 20, 2003

Genetics study tackles Lou Gehrig’s disease

By Janet Christenbury

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 the body.

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 disease.

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.