ALS Research Projects Funded by the ATSDR’s National ALS Registry

  • Large-Scale Genome-Wide Association Study of ALS.
  • The goal of this project is to identify genes that might be responsible for amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). To date, mutations in several genes have been discovered to be associated with ALS. However much still remains to be discovered. To learn more, the authors are conducting a large genetic study involving 5,000 ALS patients and a similar number of control individuals. The study will use a novel type of single nucleotide polymorphism (SNP) array focused on the exome, the protein-coding portion of the human genome. The knowledge derived from this project is expected to provide new insights into the etiology of ALS.

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  • Gene-environment Interactions in ALS.
  • The overall goal of this study is to define the role of interactions between genes and the environment in the etiology of ALS. The authors will analyze changes in high density lipoprotein (HDL) particles in the plasma and cerebrospinal fluid CSF of sporadic ALS patients. HDL particles contain enzymes and proteins that respond to environmental agents. Preliminary studies have provided evidence of some genetic associations. This study will attempt to identify a novel area of gene-environment interaction that may cause ALS.

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  • Epidemiology of ALS.
  • One goal of this research project is to better understand the distribution of ALS in the population. The authors also want to identify factors that increase the risk for getting ALS. This research prospectively studies three potential risk factors for ALS. These risk factors include military service and occupation. The authors are particularly interested in occupational exposure to lead. The authors will also evaluate cigarette smoking in the US-based National Longitudinal Mortality Study (NLMS) cohort. The NLMS cohort is a US population representative sample of over 2 million people. Over 700 people in the NLMS cohort have developed ALS.

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  • A Prospective Comprehensive Epidemiologic Study in a Large Cohort in The National ALS Registry: A Step to Identify ALS Risk Factors.
  • The goal of this study is to examine the relationship between oxidative stress (OS) and ALS. OS is shown by a combination of risk factors along with increased levels of urine OS biomarkers, and ALS disease progression, shown by function and survival. This study investigates the effect of combined exposures on development of ALS, including environmental, occupational, lifestyle, dietary, and psychological risk factors. All of these factors may increase systemic OS in patients with ALS. The hypothesis is that patients who have greater OS have faster disease progression. The relationship between OS and ALS has never been investigated.

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  • Identification and Validation of ALS Environmental Risk Factors.
  • This study has two goals. The first goal is to identify potential environmental risk factors associated with ALS. These risk factors could be exposures to toxicants in the environment or at work as well as physical exertion. Subjects will include ALS patients in the University of Michigan’s ALS Clinic and Michigan residents in the National ALS Registry. It will also include a control group. The control group will be persons without ALS who are matched on age and sex. Results from a detailed questionnaire including work and home exposures will be analyzed. The researchers will also use estimates of exposure to geographical pollutants and measure exposure biomarkers in biospecimens. These datasets will be analyzed to identify potential risk factors associated with ALS. The authors hypothesize that ALS risk may be elevated among individuals exposed to toxicants such as pesticides and/or selected fertilizers. Also, it is possible that physical exertion is a risk factor or effect modifier. The second goal is to use biomarkers to evaluate exposures using information from on questionnaires and environmental assessments. Comparisons will be made between ALS patients and control groups. Potential exposures will be assessed using the survey instrument. These exposure estimates will also use geographic information systems, environmental assessments, and biomarker data. Studying how risk factors vary with critical exposure time periods has significant potential to improve our understanding of disease pathogenesis. It could also help identify new biomarkers to aid in ALS diagnosis.

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  • Analysis of environmental risk factors for ALS using the National ALS Registry and the State-Based Comprehensive Surveillance Projects Database.
  • The goal of this study is to evaluate spatial relationships between where persons with ALS live and potential environmental risk factors for having ALS. The authors will study whether greater exposure to environmental neurotoxins/toxicants increases the risk of having ALS. This study uses geographical mapping technology. The authors will look at the relationship between places where persons with ALS live and nearby sources of toxicants. These sources include water-bodies containing cyanobacteria, sites contaminated with industrial pollutants such as Superfund and Brownfield sites and landfills, and areas using agricultural chemicals including pesticides. The authors will also evaluate the risk of getting ALS from use of water bodies for food and recreation; occupational exposures; smoking; military service; head injuries, and sports. The study may increase what we know about which environmental factors increase the risk of getting ALS. It may identify which are the most dangerous factors.

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  • Cognition, Behavior, and Caregiver Burden in ALS.
  • The goals of this study are to evaluate risk factors for PALS having cognitive and behavioral dysfunction. It will also measure how these effects impact their caregivers. The authors will look at two national cohorts of PALS: the National ALS Registry and the Department of Veterans Affairs. The authors will compare a telephone assessment with an in-person exam. One goal is develop a telephone assessment for physicians.

    This study will:

    • Characterize cognitive/behavioral subtypes
    • Identify risk factors for these subtypes
    • Study relationships among cognitive/behavioral subtypes in PALS and caregiver burden
    • Study whether these relationships affect ALS disease progression.
    • Develop and validate brief cognitive/behavioral/caregiver burden measures that can be administered over the phone.
    • Comparative neuropathological analyses among cognitive/behavioral subtypes.

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  • Prospective study of biomarkers and risk factors for ALS incidence and progression.
  • Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. ALS is characterized by a loss of the neurons that control voluntary movements. One of the molecular mechanisms that seems to contribute to ALS is oxidative stress. The purpose of this project is to identify new risk factors and biomarkers of ALS risk. We will use data and blood samples collected from a large group of over 150,000 healthy women. These women have been followed prospectively as part of the Women Health Initiative (WHI). Of the women taking part in the WHI, 121 have died of ALS. This study includes two components. The first component will test whether plasma levels of urate in apparently healthy individuals contribute to predict their ALS risk. The second component will use a metobolomic approach to look for novel risk markers of ALS. By adding the WHI cohort, we will be better able to see if there are differences in these risk markers by sex. The strengths of this study are having blood specimens before the onset of ALS and using existing specimens.

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