Pathways towards an effective immunotherapy for Parkinson’s disease

Abstract

Immunizations that target specific types of immune responses are used commonly to prevent microbial infections. However, a range of immune responses may prove necessary to combat the ravages of neurodegenerative diseases. The goal is to eliminate the ‘root’ cause of neurodegenerative disorders, misfolded aggregated proteins, while harnessing adaptive immune responses to promote neural repair. However, immunization strategies used to elicit humoral immune responses against aberrant brain proteins have yielded mixed success. While specific proteins can be cleared, the failures in halting disease progression revolve, in measure, around adaptive immune responses that promote autoreactive T cells and, as such, induce a meningoencephalitis, accelerating neurodegeneration. Thus, alternative approaches for protein clearance and neural repair are desired. To this end, our laboratories have sought to transform autoreactive adaptive immune responses into regulatory neuroprotective cells in Parkinson’s disease. In this context, induction of immune responses against modified brain proteins serves to break immunological tolerance, while eliciting adaptive immunity to facilitate neuronal repair. How to harness the immune response in the setting of Parkinson’s disease requires a thorough understanding of the role of immunity in human disease and the ways to modify such immune responses to elicit therapeutic gain. These are discussed in this review.

Keywords::

• immunization
• immunotherapy
• neurodegeneration
• Parkinson’s disease
• regulatory T cells
• T cells

Financial & competing interests disclosure

This work was supported in part by the Michael J. Fox Foundation and by NIH grants P20 DA026146, 5P01 DA028555-02, R01 NS36126, P01 NS31492, 2R01 NS034239, P20 RR15635, P01 MH64570, P01 NS43985 and 5R01 NS070190. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.