An oligomer-specific antibody improved motor function and attenuated neuropathology in the SOD1-G93A transgenic mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterized by motor neuron loss in the brain and spinal cord. Mutations in Cu-Zn superoxide dismutase (SOD1) are the first identified genetic mutations that are causative for familial ALS. Soluble SOD1 oligomers are considered the most toxic species and play a key role in the pathologic process of ALS. Here we present a therapeutic strategy for ALS with an oligomer-specific antibody (W20) targeting toxic SOD1 oligomers. Our study showed that W20 significantly improved motor neuron survival and motor performance in SOD1-G93A mouse model of ALS when administrated even at low dose within short time. Further investigation demonstrated that the beneficial effects of W20 resulted from the reduction of SOD1 oligomer levels and the inhibition of gliosis and neuroinflammation in the spinal cords and brain stems of ALS model mice. These findings for the first time suggest that an oligomer-specific antibody has promising therapeutic potential for ALS and open a new way for ALS treatment.