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

Expert Opin Ther Pat. 2009 Jul;19(7):907-17. doi: 10.1517/13543770902988530.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antibodies / immunology
  • Antibodies / therapeutic use*
  • Cattle
  • Disease Models, Animal
  • Drug Delivery Systems
  • Gene Transfer Techniques
  • Humans
  • Immunotherapy / methods*
  • Patents as Topic
  • Prion Diseases / immunology
  • Prion Diseases / therapy*
  • Prion Diseases / transmission
  • Prions / immunology

Substances

  • Antibodies
  • Prions