Antibody-based immunotherapeutic attempts in experimental animal models of prion diseases

作者:Sakaguchi Suchiro*; Ishibashi Daisuke; Matsuda Haruo
来源:Expert Opinion on Therapeutic Patents, 2009, 19(7): 907-917.
DOI:10.1517/13543770902988530

摘要

Background: There has been a dramatic decrease in the risk of transmission of bovine spongiform encephalopathy to humans. in contrast, the risk of human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) via medical treatments became potentially high since 4 vCJD cases were reported to be possibly transmitted through blood transfusion in the UK. However, no treatments are yet available for curing prion diseases. Objective: Conversion of the normal prion protein, PrP(C), to the amyloidogenic PrP, PrP(Sc), plays a pivotal role in the pathogenesis. Recently, certain anti-PrP or anti-37/67-kDa laminin receptor (LRP/LR) antibodies were shown to have the potential to cure chronically infected cells, clearing PrP(Sc) from the cells. This has raised the possibility of antibody based-immunotherapy for prion diseases. This article aims to introduce and discuss the recently published attempts of immunotherapy in prion diseases. Methods: Bibliographic research was carried out using the PubMed database. Patent literature was searched using the UK Intellectual Property Office website. Results/conclusion: No satisfying consequences in animals could be detected with anti-PrP antibodies directly infused into the brains of animals by the intraventricular route or by anti-PrP or anti-LRP/LR single chain fragment antibodies directly delivered into the brain by virus vector-mediated gene transfer. This is probably because such delivery systems failed to deliver the antibodies to the neurons relevant for the treatments.

  • 出版日期2009-7