Immunotherapeutic Studies On An Oligomer-specific Antibody And An IL-1?-targeted Vaccine In The SOD1-G93A Transgenic Mouse Model Of Amyotrophic Lateral Sclerosis

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-1(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 treatment with an oligomer-specific antibody(W20)targeting toxic SOD1 oligomers.Neuroinflammation plays a key role in the pathogenesis of ALS,which is characterized by extensive gliosis and increased level of inflammatory cytokines including IL-1?,IL-6 and TNF-?.Blockade of the key proinflammatory cytokine IL-1? may repesented as a promising therapeutic strategy for the treatment of ALS.In this study,we developed an IL-1?-targeted therapeutic vaccine consisting of an IL-1? epitope peptide(A1?)and assessed its efficacy on a SOD1-G93A mouse model of ALS.Our study showed that both W20 and A1? significantly improved motor neuron survival and motor performance,reduced SOD1 oligomer levels,inhibited gliosis and neuroinflammation in the spinal cords and brain stems of SOD1-G93 A mice.These findings for the first time suggest that oligomer-specific antibody W20 and IL-1?-targeted vaccine A1? has promising therapeutic potential for ALS and open a new way for ALS treatment.