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Impact of Geospatial Factors and Environmental Pollutants on Amyotrophic Lateral Sclerosis in the State of Michigan

地理空间因素和环境污染物对密歇根州肌萎缩侧索硬化症的影响

基本信息

批准号：
10163055
负责人：
Stephen Goutman
金额：
$ 20.21万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10163055
关键词：
ALS patients Address Affect Amyotrophic Lateral Sclerosis Blood Case-Control Studies Characteristics Clinic Clinical Collaborations Complex Cycad DNA Sequence Alteration Data Development Disease Disease Outcome Disease Progression Environment Environmental Exposure Environmental Impact Environmental Pollutants Environmental Pollution Environmental Risk Factor Epigenetic Process Excision Exposure to Functional disorder Future Genes Genetic Genetic Predisposition to Disease Genetic Risk Goals Hazardous Waste Sites Heterogeneity Incidence Individual Knowledge Measures Methods Michigan Modeling Motor Neurons Nerve Degeneration Neurodegenerative Disorders Newly Diagnosed Occupational Outcome Pathogenesis Patients Persons Phenotype Play Population Predisposition Prevalence Probability Proportional Hazards Models Public Health Questionnaires Recording of previous events Registries Regression Analysis Reporting Research Risk Risk Factors Role Site Testing Therapeutic Time Toxic Environmental Substances Universities Variant biobank biomarker discovery burden of illness disorder prevention disorder risk geographic difference improved innovation insight modifiable risk motor neuron degeneration persistent organic pollutants pleiotropism pollutant prevent translational impact

项目摘要

Project Summary/Abstract There is a fundamental gap in understanding how environmental exposures affect the development and clinical expression of amyotrophic lateral sclerosis (ALS). Continued existence of this gap represents an important problem, because until it is filled, understanding how specific environmental toxins affect the pathophysiology of ALS (1) hampers the ability to delineate ALS mechanisms and thereby limit treatment opportunities and (2) prevents the removal of modifiable risk factors from the environment. The long-term goals are to determine the influence of environmental toxins on the genetic susceptibility and pathogenesis of ALS, contextualize our data to support the National ALS registry, and promote therapeutic and biomarker discovery. The overall objective of this application is to identify persistent organic pollutants that associate with ALS disease expression. The central hypothesis is that persistent organic pollutants alter ALS incidence and disease factors such as surviv- al. The rationale for the proposed research is that discovering and delineating the impact of environmental tox- ins on ALS can identify a modifiable disease risk and also inform our understanding of the disease’s patho- physiology. Guided by strong preliminary data, this hypothesis will be tested by pursing two specific aims: 1) Determine how exposure to persistent organic pollutants modifies ALS disease expression in patients followed at the University of Michigan ALS Clinic; and 2) Expand the assessments of ALS and environmental exposures statewide to determine if geospatial clusters of ALS occur in Michigan and characterize their relationship to known sites of environmental pollution. Under the first aim the impact of environmental exposures--derived via a detailed questionnaire combined with measured persistent organic pollutant levels in blood--on region of on- set, survival, and disease progression will be determined. Under the second aim, a case-control study, com- prised of all newly diagnosed individuals with ALS and healthy controls, will determine the presence of geospa- tial clusters of ALS in State of Michigan. The proposed research is innovative, in the applicant’s opinion, be- cause it represents a substantive departure from the status quo by explicitly identifying how persistent organic pollutants alter ALS disease expression and how geospatial factors, such as persistent environmental pollu- tants, alter ALS susceptibility which will pave the way for improved pathophysiologic studies on ALS. New re- search horizons are expected to become attainable as a result. The proposed research is significant, because it will identify factors that can mitigate the risk of developing ALS and furthermore guide future studies on new pathophysiologic mechanisms of ALS. Ultimately, such knowledge has the potential to improve the pathophys- iologic understanding of ALS and other neurodegenerative diseases.

项目总结/文摘

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A 2020 centenary perspective on neuromuscular disorders.

2020 年神经肌肉疾病百年展望。

DOI：
10.1136/jnnp-2020-324327
发表时间：
2020
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
0
作者：
Goutman,StephenA;Callaghan,BrianChristopher;Feldman,Eva
通讯作者：
Feldman,Eva

Tofacitinib Suppresses Natural Killer Cells In Vitro and In Vivo: Implications for Amyotrophic Lateral Sclerosis.

DOI：
10.3389/fimmu.2022.773288
发表时间：
2022
期刊：
Frontiers in immunology
影响因子：
7.3
作者：
Figueroa-Romero C;Monteagudo A;Murdock BJ;Famie JP;Webber-Davis IF;Piecuch CE;Teener SJ;Pacut C;Goutman SA;Feldman EL
通讯作者：
Feldman EL

Diagnosis and Clinical Management of Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders.

DOI：
10.1212/con.0000000000000535
发表时间：
2017-10-01
期刊：
Continuum (Minneapolis, Minn.)
影响因子：
0
作者：
Goutman, Stephen A
通讯作者：
Goutman, Stephen A

Voicing the Need for Amyotrophic Lateral Sclerosis Environmental Research.

DOI：
10.1001/jamaneurol.2020.0051
发表时间：
2020-05-01
期刊：
JAMA neurology
影响因子：
29
作者：
Goutman SA;Feldman EL
通讯作者：
Feldman EL

Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis.

DOI：
10.1016/s1474-4422(21)00414-2
发表时间：
2022-05
期刊：
LANCET NEUROLOGY
影响因子：
48
作者：
Goutman, Stephen A.;Hardiman, Orla;Al-Chalabi, Ammar;Chio, Adriano;Savelieff, Masha G.;Kiernan, Matthew C.;Feldman, Eva L.
通讯作者：
Feldman, Eva L.