[Antibody therapy targeting ALS-linked misfolded protein]

Accumulating evidence indicates that the pathogenesis of Amyotrophic lateral sclerosis (ALS) is tightly linked to misfolding a key protein. Antibody therapy aims to eliminate or compete with the pathogenic proteins, through either passive or active immunization. We and others have generated several monoclonal antibodies (MAb)s which recognize only misfolded SOD1, but not the wild-type. Several MAbs are reported to delay the progression of mutant SOD1 Tg mice by the intraventricular application, which is mediated by different pathways. The determination of the pathogenic domain is crucial to acquire the effect of MAb therapy. Single chain of fragment of variance of IgG (scFv) is attracting emerging attention due to its broad application, in which intracellular proteins can be targeted by Intrabody or the modification of MAb with translocation signals.