Amyotrophic Lateral Sclerosis (ALS)
- Genetics and ALS
- ALS Research Review
- Collaborative Research
- National Registery
- DMPI ALS Publications
- Additional ALS Information
Genetics and ALS
Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease, is a devastating disorder characterized by progressive degeneration of the motor cells in the spinal cord and brain (central nervous system). This degeneration inhibits nerve impulses from getting to the muscles. Eventually, a person with ALS experiences muscle weakness and deterioration, particularly of the muscles used to move the arms and legs as well as those involved in speech, swallowing, and breathing. The cause is unknown, and at present there is no cure.
Approximately 90% of people with ALS (non-familial form) do not have a family history of ALS in any closely-related family members. In these individuals, the cause of ALS is complex, resulting from a combination of both genetic and environmental variables. Genes involved in the non-familial form of ALS are sometimes called susceptibility genes because they increase the risk to get the disease. Susceptibility genes are believed to interact with other genes as well as the environment to cause ALS.
The remaining 10% of individuals with ALS have the familial form of the disease, in which multiple family members are affected by ALS. The familial form of ALS includes both small families where as few as 2 family members have ALS to families with many family members with the disease. Genes that are involved in the large families with many individuals with ALS are sometimes called causative genes because they are usually sufficient to cause ALS without any other genes or factors involved. Genes involved in the smaller ALS families can either be susceptibility or causative genes.
Many genes contribute to the cause of ALS. Identifying these genes is the first step to understanding why someone gets ALS.
Our ultimate goal is to translate this information into effective treatments for ALS.
ALS Research Review
ALS research at the Duke Molecular Physiology Institute, formerly the Duke Center for Human Genetics, is multi-faceted. We work collaboratively with many different groups and institutions to find the genetic causes of ALS. We search for the genetic factors involved in both the familial and non-familial forms of ALS. We also focus specifically on those rare large ALS families that have many family members with the disease. We also study how the environment interacts with genes to cause ALS.
Some genes responsible for familial ALS are already known. For example, a gene called superoxide dismutase 1 (SOD1) located on chromosome 21q22 accounts for 20% of familial ALS. A second gene, the alsin gene (ALS2) located on chromosome 2q33, causes rare and slowly-progressive early-onset juvenile inherited ALS. Researchers at the DMPI helped identify both of these ALS genes.
Collaborative research is the key to success.
The DMPI works closely with other researchers in order to find the ALS genes. For more than 20 years, the ALS group has been collaborating with researchers at Vanderbilt University, Massachusetts General Hospital, and Northwestern University to identify the gene(s) which predispose some families to develop ALS.
Our Collaborative Amyotrophic Sclerosis Study (CALSS) has greatly extended the genetic knowledge of ALS to include genes on chromosomes 9, 16, 18, 20 and X in very large families with many family members with ALS; as well as additional genes on chromosomes 2, 7, 8, 17, 18, and 19 in the smaller and non-familial ALS cases.
National Registry of Veterans with ALS
DMPI researchers are also leading efforts to conduct a large-scale genetic study of ALS in collaboration with the VA Medical Center (VAMC) in Durham, North Carolina. Since ALS is a disease of high priority for the Department of Veterans Affairs, the VA funded the establishment of a National Registry of Veterans with ALS in 2003, which includes a DNA bank for storage of patients' blood samples. This effort is directed by the Epidemiologic Research and Information Center (ERIC) at the Durham VAMC, with cooperation from the VAMC in Lexington, KY. The ALS Association (ALSA) is advising the study leaders. All living veterans who were diagnosed with ALS and related neurodegenerative diseases were encouraged to participate in the research registry. Registry enrollment ended in September 2007 but the registry continues to conduct follow-up interviews every 6 months with living enrolled veterans. The registry has enrolled over 2100 veterans and banked over 1200 DNA samples. Collection of DNA samples will continue through March 2008. In addition to follow-up interviews the registry is focusing on helping researchers conduct multiple studies using information collected as part of the registry. There have been 12 studies approved to use registry data for epidemiological, observational and interventional protocols.
This DMPI-led study uses the Registry as a resource to specifically examine genetic and environmental risk factors for ALS in veterans. Participants in the nation-wide Registry are asked to provide information about their occupational, residential, medical, and military history, as well as other lifestyle factors (smoking, physical activity, etc.) during a telephone interview.
In addition, we are currently enrolling healthy veterans without ALS to serve as "controls." Controls are individuals who may have been exposed to similar environmental factors but did not develop the disease. These healthy veterans are asked to provide a DNA sample and complete the same telephone interview about environmental exposures.
By comparing both genetic variants and environmental exposures of veterans with and without ALS, the DMPI and VAMC researchers hope to identify factors that may trigger the development of ALS in genetically susceptible individuals.
Ultimately, we hope understanding the complex genetics of ALS will provide us with insights into the causes of this devastating disease and will help guide us to novel therapeutic opportunities.
DMPI ALS Publications
As DMPI researchers continue to define the genetic causes of ALS, they publish their findings in leading academic journals and share their knowledge with colleagues at meetings and conferences.
List of ALS Research Publications.
Additional ALS Information
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Muscular Dystrophy Association
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Phone: (602) 529-2000; (800) 572-1717