Fusogens for Axon Repair in Spinal Cord and Peripheral Nerve Injuries – Studies, Methods, and Mechanisms (systematic review with meta-analysis)

Abstract Introduction The exploration of alternative strategies for neural tissue regeneration and repair is giving rise to a novel paradigm in neurosurgery: fusogenic therapy. This approach promises rapid restoration of peripheral nerve and spinal cord function by circumventing Wallerian degeneration and eliminating the delay associated with axonal regrowth. Its potential stems from the capacity of fusogens to induce axonal fusion and achieve immediate membrane sealing, complemented by their pronounced neuroprotective properties. However, experimental data on fusogens and their effects are inconsistent, often contentious, and derived using heterogeneous methodologies. Methods We present the first comprehensive systematic review covering nearly four decades of research on fusogens for axonal membrane repair and 26 years of their experimental and clinical application in mammalian and human models for peripheral and central nervous system restoration. The review includes a meta-analysis of fusogen efficacy following traumatic spinal cord and peripheral nerve injuries. Results Conducted in accordance with the PRISMA 2020 flow protocol and PICO criteria, our analysis incorporates 86 sources, 20 of which were included in the meta-analysis. Discussion In summary, we have systematized the prevailing approaches and methods for fusogen application, delineated key contentious issues, and identified promising directions for the development of axonal fusion technology.