臨床神経学

第50回日本神経学会総会

<シンポジウム2―3>ALS治療法開発の将来ALSの免疫療法の展望

漆谷 真

滋賀医科大学分子神経科学研究センター神経難病治療学分野〔〒520-2192 滋賀県大津市瀬田月輪町〕

Emerging evidence suggests that misfolded proteins in the various neurodegenerative diseases can be targets for immunotherapy including vaccination antibody therapy. To date, vaccination strategies have been shown to be effective in Alzheimer's disease, Parkinson's disease, Huntington's disease and Prion disease. Interestingly, the subcellular localization of the target proteins varies, including cytosol, synaptosomes and extracellular spaces. We have documented that mutant SOD1 is secreted together with a neurosecretory protein chromogranin, and that vaccination against the SOD1 mutant is beneficial in delaying the onset and prolonging the lifespan. However, the mechanism of vaccination on the mutant SOD1 mice remains unclear. Moreover, vaccination induces diverse inflammatory reactions, which are reported to modify both the onset and the progression of ALS. Therefore, it is important to clarify the role of innate or acquired immunity in the pathogenesis of ALS to avoid the adverse reactions of the vaccination, and rather to apply it for amelioration. Passive immunization is also promising since only aberrant proteins can be targeted using a specific monoclonal antibody. The development of the current immunization techniques is very important for the future application, since key molecules for the sporadic ALS have emerged and are intensively investigated such as TDP-43.
Full Text of this Article in Japanese PDF (266K)

(臨床神経, 49:818−820, 2009)
key words:筋萎縮性側索硬化症, クロモグラニン, スーパーオキシドジスムターゼ1, 能動免疫, 他動免疫

(受付日:2009年5月21日)