Exposure to Neurotoxins as Risk Factors for ALS
Exposure to Neurotoxins as Risk Factors for ALS
Chemicals called neurotoxins can harm the nervous system. Amyotrophic lateral sclerosis (ALS)
 is a progressive disease affecting movement. Researchers have studied many possible causes of
 ALS, including injury, diet, and exposure to chemicals, but these studies were inconclusive.

 The purpose of this study was to determine whether exposure to lead or other neurotoxins can
 contribute to ALS. The study also evaluated lifestyle and dietary patterns. The study was
 completed in 1994-1996.

 One hundred eighty-two participants took part in this study 110 patients with ALS and 72 who
 did not have ALS. Each completed a questionnaire concerning lifestyle, diet, and residential,
 job, and medical history. Participants contributed 50 cc of blood, used to measure lead, as
 well as clippings of their toenails, used to measure mercury and other metals. They then
 underwent an XRF test (an X-ray procedure) to measure the level of lead in their shinbones
 and knees. Genes related to ALS or susceptibility to lead exposure were also evaluated.
OBJECTIVES: Stored blood and toenail samples are available from a case-control study of ALS
 conducted in 1993-1996. The purpose of the initial study was to examine the relationship to
 ALS of lead and other exposures, including mercury, pesticides, and solvents, as well as
 genetic susceptibility to these exposures. The protocol was closed in May 1997 (closed
 protocol #95-007) after recruitment of study subjects ended. The objective of the present
 proposal is to reopen the protocol to permit measurement in blood or toenails of genes,
 proteins, neurotoxicants, and other factors or agents potentially associated with ALS, as
 well as analyses of existing data. The short-term goal is to measure (i) polymorphisms in DNA
 repair genes; (ii) serum protein profiles; and (iii) serum organochlorine pesticide levels.
 Other factors may be of interest in the future, for example polymorphisms in other genes or
 levels of metals in blood or toenails. We also plan (iv) to continue analyses of existing
 data. Some data analysis will involve combining data from the original ALS study with data
 from the Harvard Normative Aging Study, a cohort study of World War II verterans that has
 collected demographic, lifestyle, and medical data as well as information on bone and blood
 lead levels.

 STUDY POPULATION: No new subjects will be recruited for this protocol. The original study
 involved 110 ALS cases, 31 hospital controls with other neurologic diseases, and 256
 population controls, recruited in New England between 1993 and 1996. The population controls
 were frequency matched to the cases on the basis of age, gender, race, and region within New
 England.

 DESIGN: The original study was a case-control study. Data collection involved an interview
 collection of blood and toenail samples, and measurement of bone lead using x-ray
 fluorescence. Stored blood and/or toenail samples are available from 107 ALS cases, 31
 hospital controls, and 39 population controls. The present study will use conventional
 techniques to measure genetic polymorphisms and serum organochlorine levels and newly
 developed SLDI-TOF technology to evaluate serum protein profiles.

 OUTCOME PARAMETERS: The outcome parameter is risk of ALS. Associations with ALS risk will be
 evaluated for polymorphisms in DNA repair genes; serum protein profiles; and organochlorine
 pesticide levels in serum.
-  INCLUSION CRITERIA:

 Cases were eligible to participate in the original study if (1) they had received a
 diagnosis of ALS within 2 years; (2) they lived in New England at least half the year; (3)
 they spoke English; (4) they were mentally and physically able to participate. The same
 inclusion criteria were used for controls.

 EXCLUSION CRITERIA:

 Potential controls were excluded if they had a physician diagnosis of a neurodegenerative
 disease, polio, post-polio syndrome, or nondiabetic neuropathy.

 Pregnant women were excluded from both case and control groups.