Granulocyte-macrophage colony-stimulating factor mRNA and Neuroprotective Immunity in Parkinson's disease. (May 2021)

• Record Type: Journal Article
• Authors: Olson, Katherine E.; Namminga, Krista L.; Lu, Yaman; Thurston, Mackenzie J.; Schwab, Aaron D.; de Picciotto, Seymour; Tse, Sze-Wah; Walker, William; Iacovelli, Jared; Small, Clayton; Wipke, Brian T.; Mosley, R. Lee; Huang, Eric; Gendelman, Howard E.
• Is Part Of: Biomaterials. Volume 272(2021)
• Publication Date: 2021-05
• Subjects: Regulatory T cells -- Neuroprotection -- GM-CSF -- mRNA -- Parkinson's disease; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2021.120786
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Restoring numbers and function of regulatory T cells (Tregs) is a novel therapeutic strategy for neurodegenerative disorders. Whether Treg function is boosted by adoptive cell transfer, pharmaceuticals, or immune modulators, the final result is a robust anti-inflammatory and neuronal sparing response. Herein, a newly developed lipid nanoparticle (LNP) containing mRNA encoding granulocyte-macrophage colony-stimulating factor ( Gm-csf mRNA) was developed to peripherally induce Tregs and used for treatment in preclinical Parkinson's disease (PD) models. Administration of Gm-csf mRNA to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mice and rats overexpressing alpha-synuclein produced dose-dependent increases in plasma GM-CSF levels and peripheral CD4+CD25+FoxP3+ Treg populations. This upregulation paralleled nigrostriatal neuroprotection, upregulated immunosuppression-associated mRNAs that led to the detection of a treatment-induced CD4+ T cell population, and decreased reactive microgliosis. The current findings strengthen prior works utilizing immune modulation by harnessing Gm-csf mRNA to augment adaptive immune function by employing a new delivery platform to treat PD and potentially other neurodegenerative disorders.