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


CONCLUSIONS
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.
Sakaguchi
Suehiro
S
The University of Tokushima, The Institute for Enzyme Research, Division of Molecular Neurobiology, 3-18-15 Kuramoto-cho, Tokushima, Japan. sakaguch@ier.tokushima-u.ac.jp
Ishibashi
Daisuke
D
Matsuda
Haruo
H
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D002417:Cattle; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D010330:Patents as Topic; D017096:Prion Diseases / Q000276:immunology / Q000628:therapy* / Q000635:transmission; D011328:Prions / Q000276:immunology
D000906:Antibodies; D011328:Prions