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

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.

Roles of fibroblast growth factors in the treatment of diabetes

“…FGF-22 plays an essential role in the recovery process of spinal cord injury, which can inhibit endoplasmic reticulum stress-induced apoptosis[ 84 , 85 ]. The rs8109113 polymorphism of the gene FGF22 has been shown to be associated with hypertension and height[ 86 ].…”

Bioinspired Approaches for Central Nervous System Targeted Gene Delivery

“…The problem of whether and how tailored overexpression of FGF22 can be used to lessen the severe functional effects of SCI has recently been studied. 59 Using a bioinspired viral vector gene delivery system, they have shown that FGF22 can promote neuronal rewiring in a circuit-specific and comprehensive manner by selectively expressing it in either long propriospinal neurons, excitatory interneurons, or a larger population of interneurons. They were also able to demonstrate that the strategy, if administered the day after the lesion or within 24 h, can restore functional recovery.…”

“…This study identified a crucial therapeutic window for the use of bioinspired viral gene transfer of FGF22 as a potential synaptogenesis therapy for SCI. 59 3.1.4. Avascular Arachnoid Barrier.…”

“…Recently, researchers discovered that the presynaptic organizer Fibroblast Growth Factor 22 (FGF22) is essential for the growth of new synapses in the developing spinal cord. The problem of whether and how tailored overexpression of FGF22 can be used to lessen the severe functional effects of SCI has recently been studied . Using a bioinspired viral vector gene delivery system, they have shown that FGF22 can promote neuronal rewiring in a circuit-specific and comprehensive manner by selectively expressing it in either long propriospinal neurons, excitatory interneurons, or a larger population of interneurons.…”

“…They were also able to demonstrate that the strategy, if administered the day after the lesion or within 24 h, can restore functional recovery. This study identified a crucial therapeutic window for the use of bioinspired viral gene transfer of FGF22 as a potential synaptogenesis therapy for SCI …”