Our findings provide evidence that in ALS the plasma concentration of TGF-beta1 increases significantly with the duration of illness. These results suggest that TGF-beta1 is involved in the disease process of ALS.

Although about 5 to 10% of amyotrophic lateral sclerosis (ALS) cases are familial, the pathophysiology of ALS remains unknown. A new point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene, resulting in an amino acid substitution of leucine84 by valine (L84V), in a Japanese patient with familial ALS (FALS) was identified. This L84V substitution was not observed in 57 normal Japanese control subjects. The enzymatic activities of Cu/Zn SOD of skin fibroblasts were significantly reduced to 75% of the control level in the affected patient. The progression of the disease with this mutation is very rapid, but the age at onset varies with sex or generation within a family.

We investigated the effects of bovine brain gangliosides on the neurotoxicity of vincristine in dissociated cultures of dorsal root ganglion cells from 10-day chick embryos. The effects of the drugs were quantified as the numbers of neurite-bearing cells or total neurite length in individual neurite-bearing cells. The administration of vincristine (1 to 1000 pg/mL) inhibited neurite outgrowth from the cells, whereas gangliosides (10 to 1000 micrograms/mL) protected them against this inhibition in a concentration-dependent manner. Electron microscopy revealed vincristine-induced fragmentation and longitudinal disorientation of microtubules in neurites and showed the protection by gangliosides against such damaging effects. Our results show that exogenous administration of gangliosides attenuates the neurotoxicity of vincristine in vitro.

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