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Studies of Environmental Risk Factors in Amyotrophic Lateral Sclerosis (ALS) and a Phase I Clinical Trial of l-Serine

Bradley, Walter G., Miller, R. X., Levine, T. D., Stommel, E. W., Cox, P. A.·2018·Neurotoxicity Research
DOI 10.1007/s12640-017-9741-x
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Abstract

β-N-Methylamino-L-alanine (BMAA) has been linked to Guam ALS/PDC and shown to produce neurodegeneration in vitro and in vivo (Drosophila, mice, rats, primates). BMAA misincorporation into neuroproteins produces protein misfolding and is inhibited by L-serine. Case-control studies in Northern New England indicate that living near to water-bodies with cyanobacterial blooms increases the risk of developing amyotrophic lateral sclerosis (ALS). The distribution of addresses of ALS cases in New Hampshire, Vermont, and Florida was compared to that of controls. Areas of statistically significantly increased numbers of ALS cases were examined for sources of environmental toxins. A phase I trial of oral L-serine was performed in 20 ALS patients (0.5 to 15 g twice daily). Safety and tolerability were assessed by comparing the rate of deterioration with 430 matched placebo controls. The distribution of residential addresses of ALS cases in New England and Florida revealed many areas where the age- and gender-adjusted frequency of ALS was greater than expected (P < 0.01). GIS studies of these "hot spots" in relation to sources of environmental pollutants, like cyanobacterial blooms, Superfund and Brownfield sites, and landfills, are ongoing. In the phase I trial of L-serine, two patients withdrew from because of gastrointestinal side effects. Three patients died during the study, which was about the expected number. The ALSFRS-R in the L-serine-treated patients showed a dose-related decre…

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Metadata

Authors
Bradley, W. G., Miller, R. X., Levine, T. D., Stommel, E. W., & Cox, P. A.
Venue
Neurotoxicity Research
Publisher
Springer Science and Business Media LLC
Published
2017-05-19
Volume
33
Issue
1
Pages
192-198
ISSN
  • 1029-8428
  • 1476-3524
DOI
10.1007/s12640-017-9741-x
Cited by
28
References
2
Language
en
Licence
Funders
  • Agency for Toxic Substances and Disease Registry (Contract 200-2014-59046, R01TS000245-01)
  • Amyotrophic Lateral Sclerosis Association (15-IIP-213)
  • Institute for Ethnomedicine (N/A)

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Bradley, W. G., Miller, R. X., Levine, T. D., Stommel, E. W., & Cox, P. A. (2018). Studies of Environmental Risk Factors in Amyotrophic Lateral Sclerosis (ALS) and a Phase I Clinical Trial of l-Serine. Neurotoxicity Research. https://doi.org/10.1007/s12640-017-9741-x