External Research funded by the National ALS Registry
The National ALS Registry is committed to advancing research. The Registry funds a wide range of research in order to better understand what may cause ALS. Read more about Registry funded research below. Additional research studies will be added as funds are available.
|No||Study Name||Institution||Investigator||Funding Period|
|University of Michigan at Ann Arbor||Stephen Goutman, MD||September, 2023 – August, 2026|
|ALS Therapy Development Foundation||Fernando Vieira, MD||September, 2023 – August, 2026|
|University of Michigan at Ann Arbor||Benjamin Murdock,PhD||September, 2022 – August, 2025|
|University of Missouri-Columbia||Xing Song,PhD||September, 2022 – August, 2025|
|President and Fellows of Harvard College||Marc Weisskopf, PhD, ScD||September, 2022 – August, 2025|
|Karolinska Institute||Fang Fang, PhD||September, 2021 – August, 2024|
|University of Michigan||Eva Feldman, MD||September, 2021 – August, 2023|
|8||Pre-disease biomarkers of persistent organic pollutants, immune system, and amyotrophic lateral sclerosis||Harvard University||Marc Weisskopf, PhD, ScD||September, 2020 – August, 2023|
|9||Serological profiling of the human virome and ALS risk in a military population||Harvard University||Alberto Ascherio, MD, DrPH||September, 2020 – August, 2023|
|10||A novel innate immunity risk factor for amyotrophic lateral sclerosis||Northwestern University||Teepu Siddique, MD, PhD||September, 2019 – August, 2020|
|11||Environmental risk factors for ALS: critical time periods and genetic interactions||Dartmouth Hitchcock Medical Center||Elijah Stommel, MD, PhD||September, 2018 – September, 2021|
|12||Metabolomic Signatures Linking ALS to Persistent Organic Pollutant Exposures||University of Michigan||Eva Feldman, MD, PhD||September, 2018 – September, 2021|
|13||Novel extracellular vesicle and molecular biomarkers of environmental exposure and disease progression in ALS||Columbia University||Neil Schneider, MD, PhD||September, 2018 – September, 2021|
|14||Identification and Characterization of Potential Environmental Risk Factors for ALS Using the ATSDR ALS Registry Cases and a Control Population||The University of Pittsburgh||Evelyn O. Talbott, DrPH||September, 2017 – September, 2020|
|15||ALS Risk in Latin Americans- A population based case control comparative study with 3 European population based cohorts||Trinity College – Dublin, Ireland||Orla Hardiman, MD, PhD||September, 2016 – September, 2018|
|16||A Population-Based Ohio ALS Repository and a Case-Control Study of ALS Risk Factors||Dartmouth College||Elijah Stommel, MD, PhD||September, 2016 – September, 2018|
|17||Environmental risk factors and gene‐environment interactions in ALS risk and progression||University of Miami||Michael Benatar, MD, PhD
Marc Weissskopf, PhD
|September, 2016 – September, 2018|
|18||Case-Control Studies Nested in National ALS Registry to Evaluate Environmental Risks||Columbia University Medical Center||Hiroshi Mitsumoto, MD, DSc||September, 2015 – August, 2018|
|19||Antecedent Medical Conditions and Medications: Associations with the Risk and Prognosis ALS||Stanford University||Lorene Nelson, PhD||September, 2015 – September, 2018|
|20||Prospective study of biomarkers and risk factors for ALS incidence and progression||Harvard School of Public Health||Alberto Ascherio, MD, DrPH||July, 2014 – June, 2015|
|21||Analysis of environmental risk factors for ALS using the National ALS Registry and the State-Based Comprehensive Surveillance Projects Database||Dartmouth College||Elijah W. Stommel, MD, PhD||July, 2014 – June, 2016|
|22||Identification and Validation of ALS Environmental Risk Factors||University of Michigan||Eva Feldman, MD, PhD||August, 2013 – August, 2017|
|23||A Prospective Comprehensive Epidemiologic Study in a Large Cohort in The National ALS Registry: A Step to Identify ALS Risk Factors||Columbia University Medical Center||Hiroshi Mitsumoto, MD, DSc||August, 2013 – August, 2017|
|24||Epidemiology of ALS||Harvard University||Marc Weisskopf, PhD, ScD||July, 2012 – June, 2013|
|25||Gene-environment Interactions in ALS||Northwestern University||Teepu Siddique, MD||July, 2012 – June, 2013|
|26||Large-Scale Genome-Wide Association Study of ALS||National Institutes of Health||Bryan Traynor, MD, PhD||July, 2012 – June, 2013|
ALS Research Projects Funded by the ATSDR’s National ALS Registry
1. Establishing the Cohort for Occupational Risk and Prevention Studies for Amyotrophic Lateral Sclerosis (ALS CORPS)
The research study from the University of Michigan at Ann Arbor will study how the ALS exposome, a lifetime of non-genetic exposures, interacts with genetics in order to inform the ALS prevention effort. The study specifically aims to look at exposures from work associated with production occupations and occupational metal exposures. The study intends to us a large longitudinal cohort of individuals with higher ALS risk based on occupational risk factors, use exposure assessment tools to identify the exposome, and finally determine the genetic risk of the cohort to integrate with exposure risk.
2. Assessment of ALS Risk Factors from ALS TDI’s Ongoing Natural History Study (n = 784)
The research study from the ALS Therapy Development Institute (ALS TDI) aims to perform a comprehensive analysis on their ongoing collection of natural history data to confirm potential risk factors or identify new ones. Once potential risk factors are identified or confirmed, ALD TDI then plans to further elucidate how these factors affect various features of ALS such as clinical diagnosis, progression, and outcomes.
3. Interactions between the microbiome, metabolome, and immune system as underlying mechanisms of ALS pathogenesis
The research study from the University of Michigan at Ann Arbor will study the mechanisms by which the gut microbiome and the immune system impact disease progression in ALS. The research team will use existing infrastructure and data pipelines from two ongoing ALS studies to identify associations between the ALS microbiome and disease metrics. The study hypothesizes that the microbial composition of ALS subjects will be associated with ALS progression as measured by ALSFRS-R (ALS functional rating scale-revised).
4. Towards Better Understanding of ALS using a Multi-Marker Discovery Approach from a Multi-Modal Database (ALS4M) National Opinion Research Center
The research study from the University of Missouri-Columbia will use machine learning to develop a method of identifying new ALS risk factors. The team intends to capitalize on the digitization of health records to develop a new hypothesis-generating model, driven by artificial intelligence and machine learning (AI/ML), to identify new risk factors and patterns for understanding, diagnosis, and treating ALS.
5. Military exposures and ALS in a large veteran population
The research study from Harvard College will study the association between military exposures and ALS in veterans using a newly linked, large database of Department of Defense (DOD) and Veterans Administration (VA) data. Data from the DOD will include military factors such as service branch, military occupation, deployment, demographic, and health data. Specifically, the team will also look at data on traumatic brain injuries (TBI) captured in conflict or elsewhere. Data from the VA will provide more in-depth medical history of veterans who receive health care at the VA; the team will specifically look at the effect of statin use on ALS incidence. The use of the large DOD-VA DaVINCI database of 4 million veterans gives the team an unprecedented setting to assess the link between military exposures and ALS.
6. Identify and Evaluate Potential Risk Factors for Amyotrophic Lateral Sclerosis – A Unique Contribution from Sweden
The research study from Karolinska Institute will look at military services, traumatic brain injuries (TBI), chronic neuroinflammation, and infections as potential risk factors for ALS. The study will first use data and biospecimens collected in a Swedish national ALS Registry to identify potential risk factors and their underlying interactions with genetic susceptibility, chemical exposures, and gut microbiome. The study will further attempt to replicate their finding in the ATSDR’s National ALS Registry. Finally the study will develop a molecular phenotyping-based tool to allow for more accurate predictions of ALS disease progression. This study expects to advance the understanding of ALS as a disease and help ATSDR better prioritize future projects and initiatives.
7. Linking long-term air pollution exposure with inflammation, ALS risk, and disease progression
The research study from the University of Michigan will investigate long-term air pollution as a potential risk factor to ALS. The study aims to use existing prediction models of key ambient air pollutants (PM2.5, NO2, and traffic related air pollutants) to estimate exposures for cases and controls in the University of Michigan ALS patient biorepository and investigate how these exposures associate with ALS risk. The study will further examine the immune profiles of exposure cases and explore whether the identified immune profiles are associated with ALS risk and disease progression. The study aims to use its findings to help guide prevention efforts, therapeutic targets, and blood-based biomarkers for clinicals studies using knowledge gained.
8. Pre-disease biomarkers of persistent organic pollutants, immune system, and amyotrophic lateral sclerosis
The research study from the Harvard School of Public Health will measure the levels of persistent organic pollutants (POPs) in blood samples of persons with ALS that were collected before the onset of ALS to learn if pre-ALS POPs levels are associated with the risk of developing ALS and survival with ALS. The POPs levels will be measured from pre-ALS blood samples taken from men and women who participated in Finnish and Danish health and diet surveys. The research study will then explore if changes to immune response cells in these samples occurred prior to ALS onset and, if so, learn whether these changes to the immune response cells resulted from POPs exposures or caused ALS. The study hypothesizes that higher pre-ALS POPs levels increase the risk of developing ALS, decrease survival with ALS, and cause changes to immune response cells in persons with ALS.
9. Serological profiling of the human virome and ALS risk in a military population
The research study from the Harvard T.H. Chan School of Public Health will examine blood samples collected from healthy U.S. armed forces service members, including persons who later developed ALS and persons who remained healthy. The research team will examine these samples for antibodies against more than 400 viruses in order to learn whether any of these the viruses were associated with ALS. The study will then measure biomarkers that show neuron cell damage to learn if the viral infections were associated with neuron damage in these servicemembers. Finally, the study will explore how traumatic brain injury, military deployment history, smoking, body mass index, diabetes, and family history of ALS may affect viral infection and ALS risk. The study hypothesizes that ALS may result from a combination of viral infection and a person’s immune response to the viral infection.
10. A novel innate immunity risk factor for amyotrophic lateral sclerosis
The research study from the Northwestern University at Chicago will look for genetic variants of an innate immunity protein called apolipoprotein L1 (APOL1) in DNA and RNA samples of North American ALS patients. The research study will then determine whether increased levels of these variant APOL1 proteins exist in ALS patients. The study hypothesizes that increased expression of APOL1 variant proteins may contribute to ALS due to damage that some neurons receive after APOL1 is activated in response to a trypanosome infection. The research study will explore whether these ALS patients had past trypanosome infections and then evaluate the relationship between ALS variant expression, past trypanosome infections, and environmental factors, including occupational and geographic exposure to trypanosomes.
11. Environmental risk factors for ALS: critical time periods and genetic interactions
The research study from Dartmouth College will investigate the most susceptible time periods during which environmental exposures carry the greatest risk for later development of ALS, by using residential history to estimate exposures to waterbody cyanobacteria, pesticides, and polluted sites in ALS patients compared to healthy controls in time-linked databases. The research team will also develop a pooled genotype dataset derived from genetic variants implicated in neurodegenerative illness on ATSDR National ALS Biorepository and Dartmouth College northern New England control and ALS specimens to evaluate gene x environment interactions in ALS risk. The study outcomes will reveal genetic variants that raise ALS susceptibility, and determine the periods of life that carry the greatest risk for developing ALS from exposures to environmental stressors.
12. Metabolomic Signatures Linking ALS to Persistent Organic Pollutant Exposures
The research study from the University of Michigan proposes to identify the metabolomic signatures that correlate with persistent organic pollutant (POP) exposures and historical exposure risk factors, and determine whether these are associated with ALS progression. The study hypothesizes that POP exposures will lead to conserved metabolite changes in plasma and in end stage central nervous system tissue.
13. Novel extracellular vesicle and molecular biomarkers of environmental exposure and disease progression in ALS
The research study from the Columbia University Health Sciences will validate new non-invasive methods to identify the toxic exposures to which ALS patient brains could be exposed, and to elucidate which mechanisms link toxic exposures and disease progression. The study will be the first to evaluate whether central nervous system derived extracellular vesicles can be potentially used as novel biomarkers of environmental exposures and disease progression in ALS. The research investigators will test biospecimens from persons with ALS for metals and non-persistent pesticides, while matching exposure- and patient-specific transcriptomic signatures to ALS signaling pathways.
14. Identification and Characterization of Potential Environmental Risk Factors for ALS Using the ATSDR ALS Registry Cases and a Control Population
The research study will examine environmental toxicants from ambient air pollution in persons with ALS from the ATSDR National ALS Registry and non-ALS controls using information in blood and provided from self-report questionnaires on occupational and non-occupational exposures. The proposed study will be one of the first to examine serum/plasma levels of ambient air environmental toxicants in combination with data on environmental and occupational exposures from interview data in relation to ALS risk.
15. ALS Risk in Latin Americans- A population based case control comparative study with 3 European population based cohorts
ALS is a rare and complicated disease. ALS likely results from the interaction of two risk factors. These risks include factors people are born with (genetic) and factors from the environment. Genetic risks can be studied by ancestral origin. Environmental risks can be studied by geographical origin. The purpose of this study is to compare two populations with different genetic and environmental risks. It has been suggested that the Hispanic population in North America has lower rates of ALS. In effort to understand if and why the Hispanic population in North and South America is protected from ALS, we will compare this population to Europeans. We will compare the rates, features, and risks of ALS. The risks of ALS will be studied by ancestral origin (genetic) and geographical origin (environment). This study may help us understand genetic and environmental risks that cause ALS.
16. A Population-Based Ohio ALS Repository and a Case-Control Study of ALS Risk Factors.
We don’t know the causes of Lou Gehrig’s disease (also called ALS). If we can find the causes, we might be able to cure ALS. One clue is to learn what people with ALS have been exposed to in the past. If ALS patients have been exposed to more of a certain chemical than people who do not have ALS, then that chemical may possible be a cause of ALS. The environment in Ohio has high concentrations of many of the chemicals that have been suggested to cause ALS. Some of the chemicals suggested to cause ALS are pesticides, algal blooms in lakes (“green scum”), and chemicals released by factories. We are going to contact all the people with ALS living in Northern and Central Ohio and ask them to answer a series of questions about what they may have been exposed to. We are also going to contact a series of people who do not have ALS (these are called “control subjects”) and ask them the same questions. By comparing the answers, we hope to find what chemicals are likely to cause ALS. We will also collect the addresses of the ALS patients and control subjects. We will look at sources of environmental pollutants near their homes. If ALS patients are more likely to live near a specific source than control subjects, then the chemicals released from such sources may be linked to ALS.
17. Environmental risk factors and gene‐environment interactions in ALS risk and progression.
Amyotrophic lateral sclerosis (ALS) is a complicated disease. ALS likely results from a complex relationship between risk people are born with (genetic) and risk from the environment. More and more, it is thought that the risk of developing ALS is separate from how quickly the disease gets worse. Little is known about the factors in the environment that affect ALS. This study will look at those factors and their relationship to genes on how ALS works once someone has it. We will also look at the effect of that relationship on how likely a person is to develop ALS. This study will be done thanks to the Clinical Research in ALS and related disorders for Therapeutic Development (CReATe) Consortium that is a part of the Rare Diseases Clinical Research Network (RDCRN). RDCRN is funded by the NIH. We will add our new data to the data that CReATe will collect on about 300 patients with ALS. We will use new and original ways to look at that data. This work will also serve as a model for future use of the environmental data being collected online by the National ALS Registry. As a result, this work meets the goals of the registry, which collects data from people that already have ALS. It also looks to the future, as the registry may begin to collect data on ALS patients over time and begin to bank samples (including DNA) from people.
18. Case-Control Studies Nested in National ALS Registry to Evaluate Environmental Risks.
People now think ALS could be caused by a combination of both genetic and environmental risk factors. We will study whether individual environmental risk factors reported to be linked with ALS act through a common mechanism. This common mechanism is oxidative stress (OS). We will conduct a set of case-control studies nested within ARREST ALS of the National ALS Registry. We will evaluate environmental and other risk factors. The cases (150 patients) will be identified in the ongoing ARREST ALS project. We will match two controls to each case based on sex, age (± 5 years), race/ethnicity, and geographic area of residence. We will analyze risk factors at different stages of life. This study could help find entirely new and unique data concerning environmental risk factors, disease progression, and the potential cause(s) of ALS.
19. Antecedent Medical Conditions and Medications: Associations with the Risk and Prognosis ALS.
ALS affects people in the middle to late years of their lives. This is a time of life where it is common to have more than one health problem. There is little known about how chronic medical conditions and drugs may impact susceptibility to ALS. There is mounting concern and recent evidence that certain medical conditions and drugs are linked with an increased risk of developing ALS. Other conditions and drugs might protect against getting ALS. This study will look at the role of hyperlipidemia, diabetes, autoimmune diseases, as well as the drugs used to treat these disorders, as both risk and prognostic factors for ALS. This study has three specific aims. The first aim is to look at the association between other medical conditions and the risk of developing ALS. The second aim is to look at the relationship between certain classes of drugs and the risk of developing ALS. And the third aim is to see if medical conditions or drugs a person has at the time of ALS diagnosis changes survival. Investigators at Stanford University will study a group of people who have Medicare fee-for-service coverage. This study will help the researchers see if metabolic conditions, autoimmune, diseases and commonly used drugs affect the risk of getting ALS. It will also look at if these factors change the length of survival after diagnosis with ALS.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
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.