Immunotherapy against Prion Disease.

Yue Ma,Jiyan Ma

doi:10.3390/pathogens9030216

Abstract

The term “prion disease” encompasses a group of neurodegenerative diseases affecting both humans and animals. Currently, there is no effective therapy and all forms of prion disease are invariably fatal. Because of (a) the outbreak of bovine spongiform encephalopathy in cattle and variant Creutzfeldt–Jakob disease in humans; (b) the heated debate about the prion hypothesis; and (c) the availability of a natural prion disease in rodents, the understanding of the pathogenic process in prion disease is much more advanced compared to that of other neurodegenerative disorders, which inspired many attempts to develop therapeutic strategies against these fatal diseases. In this review, we focus on immunotherapy against prion disease. We explain our rationale for immunotherapy as a plausible therapeutic choice, review previous trials using either active or passive immunization, and discuss potential strategies for overcoming the hurdles in developing a successful immunotherapy. We propose that immunotherapy is a plausible and practical therapeutic strategy and advocate more studies in this area to develop effective measures to control and treat these devastating disorders.

Highlights

Prion diseases, known as transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative disorders affecting both humans and animals [1,2]
The well-publicized vCJD is believed to result from the consumption of beef products derived from bovine spongiform encephalopathy (BSE) affected cattle [4], illustrating the zoonotic potential of animal prion disease
The treatment was not effective when the antibody treatment was started at later stages of prion infection or when mice were infected via intracerebral prion inoculation, indicating that these antibodies are unable to cross the blood–brain barrier to stop disease progression in the central nervous system (CNS)

Summary

Background

Known as transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative disorders affecting both humans and animals [1,2]. Most cases of prion diseases are sporadic, including sporadic Creutzfeldt–Jakob disease (CJD) and sporadic fatal insomnia. About 5–15% of prion disease cases are genetic (dominantly inherited), including familial CJD, fatal familial insomnia (FFI), and Gerstmann–Sträussler–Scheinker syndrome (GSS). The most important pathogenic feature of PrPSc is its ability to seed the conversion of naïve PrPC into PrPSc , which forms the basis for prion infectivity. The adaptation of a prion strain to the new host, i.e., acquiring new biochemical and/or pathogenic properties, is known as strain mutation or evolution [9,12]. We focus our discussions on the immunological approaches against prion disease

Why Is Immunotherapy a Plausible Choice for Prion Disease?

Active Immunization against Prion Diseases

Passive Immunization against Prion Diseases

Findings

Conclusions