Exogenous Toxicants and Genetic Susceptibility in ALS
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal neurodegenerative disease that poses a significant burden for affected individuals and their family members. The principal objective of this epidemiologic study is to identify environmental and genetic risk factors for ALS. Of primary interest is whether environmental chemicals such as heavy metals, pesticides and organic solvents contribute to the cause of ALS. We also aim to identify genetic factors that contribute to the risk of ALS because individuals with certain genetic traits may be unable to protect against the toxic effects of chemical exposure. Other factors that may protect against the development of ALS, such as dietary antioxidants, are also under investigation. If modifiable factors affecting the risk for ALS could be identified, interventions to delay or even prevent the development of ALS could be developed.
The principal objective of this study is to identify environmental and/or genetic risk factors for amyotrophic lateral sclerosis (ALS). We are addressing this objective by conducting a case-control study of ALS in the Northern California Kaiser Permanente Medical Care Program (KPMCP). Over a four-year period, approximately 175 persons newly diagnosed with ALS will be identified and recruited through physician referrals and computerized mechanisms available within the Kaiser system. The patients with ALS will be compared to a sample of 350 age- and gender-matched persons without ALS from the same membership. Specific study aims are as follows: (1) to investigate the association of ALS with exposure to neurotoxicants including lead, other heavy metals, solvents and pesticides; (2) to determine whether inadequate oxidative defenses for protecting against free-radicals enhance the toxicity of exogenous exposures; (3) to examine the evidence for familial aggregation of neurodegenerative diseases among first-degree relatives of patients with ALS; and (4) to estimate the incidence of ALS in diverse racial and ethnic groups.
Observational Model: Defined Population, Observational Model: Natural History, Time Perspective: Cross-Sectional, Time Perspective: Retrospective
Amyotrophic Lateral Sclerosis
National Institute of Environmental Health Sciences (NIEHS)
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00011154
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.
Motor Neuron Disease
Diseases characterized by a selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In AMYOTROPHIC LATERAL SCLEROSIS there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes (see MUSCULAR ATROPHY, SPINAL) the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy (BULBAR PALSY, PROGRESSIVE), the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation. (Adams et al., Principles of Neurology, 6th ed, p1089)
Diseases characterized by the presence of abnormally phosphorylated, ubiquitinated, and cleaved DNA-binding protein TDP-43 in affected brain and spinal cord. Inclusions of the pathologic protein in neurons and glia, without the presence of AMYLOID, is the major feature of these conditions, thus making these proteinopathies distinct from most other neurogenerative disorders in which protein misfolding leads to brain amyloidosis. Both frontotemporal lobar degeneration and AMYOTROPHIC LATERAL SCLEROSIS exhibit this common method of pathogenesis and thus they may represent two extremes of a continuous clinicopathological spectrum of one disease.
Amyotrophic Lateral Sclerosis
A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94)
Bulbar Palsy, Progressive
A motor neuron disease marked by progressive weakness of the muscles innervated by cranial nerves of the lower brain stem. Clinical manifestations include dysarthria, dysphagia, facial weakness, tongue weakness, and fasciculations of the tongue and facial muscles. The adult form of the disease is marked initially by bulbar weakness which progresses to involve motor neurons throughout the neuroaxis. Eventually this condition may become indistinguishable from AMYOTROPHIC LATERAL SCLEROSIS. Fazio-Londe syndrome is an inherited form of this illness which occurs in children and young adults. (Adams et al., Principles of Neurology, 6th ed, p1091; Brain 1992 Dec;115(Pt 6):1889-1900)
OBJECTIVES: I. Determine specific clinical features, molecular abnormalities, and laboratory-based biological markers of free radical stress that are associated with amyotrophic lateral...
The purpose of this study is to investigate the efficacy and confirm the safety of E0302 in patients with Amyotrophic Lateral Sclerosis (ALS) by assessing changes in scores of survival rat...
This research is being done to see if the ketogenic diet (which is high in fat and low in carbohydrates) is safe and tolerable in amyotrophic lateral sclerosis (ALS) patients who are fed t...
The purpose of this trial is to test the safety, tolerability, and effectiveness of minocycline compared to placebo in patients with amyotrophic lateral sclerosis (ALS).
Specific aims: Aim 1. To determine the incidence of hypoventilation in Amyotrophic Lateral Sclerosis (ALS) patients. Aim 2. To identify the clinical characteristics and risk facto...
Clinical evidence for parkinsonism may accompany Amyotrophic Lateral Sclerosis with a frequency ranging from 5% to 17%. The concurrence of Amyotrophic Lateral Sclerosis and Parkinson's disease, outsid...
Acquired neuromyotonia encompasses a group of inflammatory disorders characterized by symptoms reflecting peripheral nerve hyperexcitability, which may be clinically confused in the early stages with...