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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 decrease in the rate of progression (34% reduction in slope, P = 0.044). The non-random distribution of addresses of ALS patients suggests that residential exposure to environmental pollutants may play an important role in the etiology of ALS. l-Serine in doses up to 15 g twice daily appears to be safe in patients with ALS. Exploratory studies of efficacy suggested that l-serine might slow disease progression. A phase II trial is planned. [ABSTRACT FROM AUTHOR]

Current treatments for anti-GM1 ganglioside or antimyelin-associated glycoprotein (anti-MAG) antibody-associated polyneuropathies are toxic or very costly. In this preliminary study the authors treated five patients with neuropathy and immunoglobulin M antibodies to GM1 ganglioside or MAG by depleting B cells using Rituximab--a monoclonal antibody directed against the B-cell surface membrane marker CD20. Within 3 to 6 months after treatment, all five patients had improved function, significantly increased quantitative strength measurements, and reduced titers of serum autoantibodies.

Mammalian cDNAs encoding a rat (Rel-N1) and a human (Hel-N1) neuronal RNA-binding protein have been cloned and characterized with respect to tissue specificity, neuroanatomical localization, and RNA binding specificity. Both proteins are highly similar to the product of the Drosophila elav gene, which is expressed in all neurons of the fly and is required for development of the nervous system. However, in situ hybridization of rat tissues demonstrated more restricted expression of Rel-N1 mRNA within a subset of neurons of the hippocampus, cortex, and other regions of the gray matter, but not in glial cells or white matter. In vitro RNA binding experiments demonstrated that Hel-N1 can bind to the 3' untranslated region (3' UTR) of Id mRNA, a transcript that encodes a helix-loop-helix transcriptional repressor that is abundantly expressed in undifferentiated neural precursors. Sequences characterized for Hel-N1 binding were also abundantly present in the 3' UTR of the Drosophila extramacrochaetae mRNA, which encodes an Id homolog. Thus, we have identified a potential link between a neuronal 3' UTR RNA-binding protein and regulatory transcription factors involved in neural development. These findings are interpreted in light of recent studies in which mRNA 3' UTRs were found to be important for the regulation of cell growth and differentiation.