Experimental immune-mediated motor neuron diseases: Models for human ALS

Amyotrophic lateral sclerosis is an idiopathic, utlimately fatal disease, clinically manifest as progressive weakness and spasticity, associated with the loss of motoneurons. Circumstantial evidence supports a role for autoimmune processes in the progression of this human disorder. Two immune-mediated animal models have been developed in our laboratory for motor neuron loss. Experimental autoimmune motor neuron disease is a lower motor syndrome induced in guinea pigs by the repeated injection of a purified bovine spinal motor neuron antigen. Affected animals demonstrate extremity weakness, associated with electromyographic and morphologic evidence of denervation, a loss of spinal cord motor neurons, high antibody titers against motor neurons, and localization of IgG immunoreactivity to the neuromuscular junction and motor neuron cytoplasm. Experimental autoimmune grey matter disease is a more acute and severe disorder involving both upper and lower motor neurons, induced in guinea pigs by inoculation of a bovine ventral spinal cord homogenate, in which scattered foci of denervation are observed in the motor cortex and ventral spinal cord. Similarities between these diseases and human ALS are reviewed.