Inhibition of terminal axonal sprouting by serum from patients with amyotrophic lateral sclerosis

To investigate the pathogenesis of amyotrophic lateral sclerosis, we compared the effect of serum from patients with this disease on the regenerative sprouting of terminal axons in botulinum-treated mouse gluteus muscle with the effects of serum from controls and from patients with diabetic peripheral neuropathy. Serum from 9 of 19 patients with the sporadic form of amyotrophic lateral sclerosis and from 2 of 6 patients with the familial form caused a reduction in the proportion of sprouting terminal axons, as compared with that found in muscles treated with serum from controls or diabetic patients. Immunoglobulin from patients with amyotrophic lateral sclerosis, when tested on immunoblots, recognized a 56-kilodalton protein secreted by denervated rat diaphragm muscle; rabbit antiserum raised against this protein also suppressed terminal axonal sprouting. Thus, we have detected an antibody in the serum of patients with amyotrophic lateral sclerosis that inhibits sprouting of neurons and subsequent reinnervation of skeletal muscle. Whether this antibody is of primary pathogenic importance or represents a secondary response to neuromuscular destruction is not known. In either case, serum from patients with amyotrophic lateral sclerosis may provide reagents for studies of the trophic communications between muscle and motor neurons.