Mouse inoculation studies reveal no transmissible agent in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) resembles the spongiform encephalopathies in its dual pattern of inherited and sporadic cases, its uniform prevalence in different populations, its late onset (suggestive of a long incubation period) and its pathological picture of neuronal degeneration without inflammation. There is a well-established protocol for primary transmission of scrapie and related diseases to mice. Using this, we inoculated four longlived, inbred, mouse strains with cord material fresh-frozen within three hours of death, from a case of ALS or a control case. No motor neuron loss, gliosis or tract demyelination was found in the experimental group. Fifty per cent of each group were observed for more than 600 days. Two types of lesions were found in these animals at death: widespread foci of white matter vacuolation and bilateral thalamic mineral deposits. They were present in the control group at the same incidence and severity as in the experimental group and were thus considered to represent an age-related change. Attention is drawn to them because they have been claimed as significant when found in a transgenic model of spongiform encephalopathy. The results of our carefully-controlled experiment suggest that it is unlikely that ALS is caused by a scrapie-like agent capable of transmission to mice.