Rinsho Shinkeigaku (Clinical Neurology)

The 50th Annual Meeting of the Japanese Society of Neurology

Future perspectives of immunotherapy against ALS

Makoto Urushitani

Unit for Neurobiology and Therapeutics Molecular Neuroscience Research Center Shiga University of Medical Science

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)

(CLINICA NEUROL, 49: 818|820, 2009)
key words: amyotrophic lateral sclerosis, chromogranin, superoxide dismutase 1, active immunization, passive immunization

(Received: 21-May-09)