Molecular Mechanisms for Neural Restoration and the Role of Gene Therapy for the Treatment of Paralysis

Review article

Abstract

Paralysis is one of the most debilitating neurological conditions, which can occur due to traumatic injury or degenerative processes within the central nervous system. Earlier the treatment was limited to symptomatic management and physical rehabilitation, which failed to address the underlying cellular destruction. The research on molecular regeneration through gene therapy indicates a shift toward curative interventions. This review provides the current knowledge regarding the genetic modulation of damaged neural circuits to promote axonal regrowth and functional recovery. The regenerative capacity of the adult central nervous system is severely limited by a complex inhibitory environment and the intrinsic loss of growth potential in mature neurons. Genetic interventions aim to overcome these barriers by delivering neurotrophic factors, silencing growth-inhibitory pathways, and utilizing precise genome editing tools like CRISPR-Cas9. Viral vector systems, particularly adeno-associated viruses, have demonstrated high efficacy in delivering therapeutic transgenes to specific neuronal populations. Preclinical models indicate that modulating the PTEN/mTOR pathway and enhancing the expression of brain-derived neurotrophic factor can trigger significant axonal sprouting and synaptic reconnection. The integration of molecular biology with neural engineering offers a plausible path toward reversing permanent paralysis while clinical translation faces hurdles regarding delivery across the blood-brain barrier and the management of host immune responses. This review shows the transition from palliative care to a molecular-driven paradigm of neural repair