Unleashing the potential of mRNA therapeutics for inherited neurological diseases.

Autor:	Monfrini E; Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy., Baso G; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy., Ronchi D; Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy., Meneri M; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy.; Stroke Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy., Gagliardi D; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy., Quetti L; Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy., Verde F; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy.; Department of Neurology, Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy., Ticozzi N; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy.; Department of Neurology, Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy., Ratti A; Department of Neurology, Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy.; Department Medical Biotechnology and Translational Medicine, University of Milan, Milan 20100, Italy., Di Fonzo A; Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy., Comi GP; Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy., Ottoboni L; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy., Corti S; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan 20122, Italy.; Department of Neuroscience, Neuromuscular and Rare Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2024 Sep 03; Vol. 147 (9), pp. 2934-2945.
DOI:	10.1093/brain/awae135
Abstrakt:	Neurological monogenic loss-of-function diseases are hereditary disorders resulting from gene mutations that decrease or abolish the normal function of the encoded protein. These conditions pose significant therapeutic challenges, which may be resolved through the development of innovative therapeutic strategies. RNA-based technologies, such as mRNA replacement therapy, have emerged as promising and increasingly viable treatments. Notably, mRNA therapy exhibits significant potential as a mutation-agnostic approach that can address virtually any monogenic loss-of-function disease. Therapeutic mRNA carries the information for a healthy copy of the defective protein, bypassing the problem of targeting specific genetic variants. Moreover, unlike conventional gene therapy, mRNA-based drugs are delivered through a simplified process that requires only transfer to the cytoplasm, thereby reducing the mutagenic risks related to DNA integration. Additionally, mRNA therapy exerts a transient effect on target cells, minimizing the risk of long-term unintended consequences. The remarkable success of mRNA technology for developing coronavirus disease 2019 vaccines has rekindled interest in mRNA as a cost-effective method for delivering therapeutic proteins. However, further optimization is required to enhance mRNA delivery, particularly to the CNS, while minimizing adverse drug reactions and toxicity. In this comprehensive review, we delve into past, present and ongoing applications of mRNA therapy for neurological monogenic loss-of-function diseases. We also discuss the promises and potential challenges presented by mRNA therapeutics in this rapidly advancing field. Ultimately, we underscore the full potential of mRNA therapy as a game-changing therapeutic approach for neurological disorders. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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