Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia

Molecular Therapy : the Journal of the American Society of Gene Therapy
Françoise PiguetHélène Puccio

Abstract

Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Here, we report a new conditional mouse model with complete frataxin deletion in parvalbumin-positive cells that recapitulate the sensory ataxia and neuropathy associated to FA, albeit with a more rapid and severe course. Interestingly, although fully dysfunctional, proprioceptive neurons can survive for many weeks without frataxin. Furthermore, we demonstrate that post-symptomatic delivery of frataxin-expressing AAV allows for rapid and complete rescue of the sensory neuropathy associated with frataxin deficiency, thus establishing the pre-clinical proof of concept for the potential of gene therapy in treating FA neuropathy.

Citations

Jan 11, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·David R LynchElizabeth Kichula
Dec 16, 2018·The Journal of Biological Chemistry·Jiun-I LaiElisabetta Soragni
Feb 1, 2020·Journal of Neurology·J GandiniM Strupp
Jul 30, 2020·Antioxidants·Laura R RodríguezJuan Antonio Navarro Langa
Mar 6, 2019·Frontiers in Neuroscience·José Vicente LlorensMaría Dolores Moltó
May 30, 2020·International Journal of Molecular Sciences·Deborah ChiabrandoEmanuela Tolosano
Oct 28, 2019·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Lise LegrandFrancoise Pousset
Sep 11, 2020·Expert Review of Neurotherapeutics·Theresa A ZesiewiczJoshua Vega
Jul 19, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Joel M Gottesfeld
Jul 11, 2018·International Journal of Molecular Sciences·Véronique MonnierJuan Antonio Navarro
Dec 20, 2019·Annals of Clinical and Translational Neurology·Gilles NaeijeXavier P De Tiège
Feb 6, 2020·Frontiers in Oncology·Veronica FioritoEmanuela Tolosano
Nov 20, 2020·Molecular Therapy. Methods & Clinical Development·Brahim BelbellaaHélène Puccio
Jan 13, 2021·Neurodegenerative Disease Management·David R Lynch, Joseph Johnson
Jan 13, 2021·Human Molecular Genetics·Layne N RoddenSanjay I Bidichandani
Apr 14, 2020·Neurologic Clinics·Kimberly Tsu Kwei, Sheng-Han Kuo
Mar 7, 2021·International Journal of Molecular Sciences·Gabriel Ocana-SanteroSaúl Herranz-Martín
Nov 27, 2019·Molecular and Cellular Neurosciences·Anna Stepanova, Jordi Magrané
Jun 12, 2021·Disease Models & Mechanisms·Marlies P RossmannLeonard I Zon
Aug 8, 2021·International Journal of Molecular Sciences·Beata TarnackaMaria Maślińska
Jun 2, 2020·Molecular Therapy. Methods & Clinical Development·Pedro Silva-PinheiroCarlo Viscomi
Sep 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Abraham J Paredes-FuentesRafael Artuch

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