Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury

Aljović, Almir; Jacobi, Anne; Marcantoni, Maite; Kagerer, Fritz; Loy, Kristina; Kendirli, Arek; Bräutigam, Jonas; Fabbio, Luca; Van Steenbergen, Valérie; Pleśniar, Katarzyna; Kerschensteiner, Martin; Bareyre, Florence M (2023): Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury. EMBO Molecular Medicine, 15 (2). ISSN 1757-4676

Abstract

Functional recovery following incomplete spinal cord injury (SCI) depends on the rewiring of motor circuits during which supraspinal connections form new contacts onto spinal relay neurons. We have recently identified a critical role of the presynaptic organizer FGF22 for the formation of new synapses in the remodeling spinal cord. Here, we now explore whether and how targeted overexpression of FGF22 can be used to mitigate the severe functional consequences of SCI. By targeting FGF22 expression to either long propriospinal neurons, excitatory interneurons, or a broader population of interneurons, we establish that FGF22 can enhance neuronal rewiring both in a circuit-specific and comprehensive way. We can further demonstrate that the latter approach can restore functional recovery when applied either on the day of the lesion or within 24 h. Our study thus establishes viral gene transfer of FGF22 as a new synaptogenic treatment for SCI and defines a critical therapeutic window for its application.

• Doc-Type: Article (LMU Hospital)
• Organisational unit (Faculties): 07 Medicine > Medical Center of the University of Munich > Neurological Clinic and Polyclinic with Friedrich Baur Institute
• DFG subject classification of scientific disciplines: Life sciences
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 408885537
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 118803580
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 390857198
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892