The potential application of gene therapy in the treatment of traumatic brain injury

Abstract

Advances in molecular biology have allowed the possibility of using gene therapy in the treatment of traumatic brain injury. The major tactics involve picking out the appropriate gene target and, by controlling its specific regional expression, inhibiting neuronal cell deaths and/or promoting neuronal regeneration. This review addresses the preliminary usage of gene therapy in in vitro experiments and in animal models to treat traumatic brain injury. The gene targets with therapeutic potentials, the vectors that can be employed to deliver the candidate genes, as well as different approaches for gene therapy are discussed in detail in this review. Despite the existence of several major obstacles to making it practical and effective, gene therapy could provide a new strategy for treatment of the traumatically injured brain.

Localized cell and drug delivery for auditory prostheses

“…Similar research on the central nervous system has yielded compounds including anti-apoptotic agents, amino acids, neurotransmitter receptor agonists, antioxidants, anti-inflammatory agents, calcium, hormones, and growth factors which are useful in promoting the survival of neurons in many traumatic and neurodegenerative states (Chin and D'Mello, 2005;Diem et al, 2007;Friedman, 2006;Hara, 2007;Hoffman et al, 2006;Lescot et al, 2006;Sweeney, 1997). Cell delivery, gene therapy, and tissue engineering approaches to repairing traumatic injury and diseases of the brain and central nervous system have also produced promising results for the regeneration of lost neurons (Buch et al, 2007;Mochizuki, 2007;Shen et al, 2007).…”

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

“…High neuroprotective potential, promotion of growth, survival and differentiation of neuronal cells [230] GDNF-adenoviral delivery, gene transfer via AAV8, transfer of calbindin D gene via HSV, NGF expression via transferrin-associated cationic liposome/ Tf-lipoplexes Caused attenuation in traumatic injury in focal cortex and these include [231] AAV-based overexpression of S6K1 or AKT Therapeutic effect by mTOR signaling activation [231] The IGF-1 secreting modified NPC produced similar effects in rodent models [262]. The FGF-2 producing modified embryonic mesencephalic progenitor cells of the rat could not enhance the functions or survival of dopaminergic neurons in rats with 6-OHDA lesions showing every trophic factor does not show neuroprotective action [263].…”

“…TBI is known to express genes both that are selfdestructing and protective genes. Hence, targeting on specific genes responsible for the pathogenesis of TBI can block the cell death and aid in self-repair of the neurons [231]. Gene level studies in TBI include determining the expression of the NTF (NGF), proapoptotic, and anti-apoptosis proteins in Bcl-2 family, heat shock protein (HSP-60, 72, 32), and zinc finger protein (A20).…”

“…Potentiating pro-inflammatory vectors can cause progression of injury which can be evaluated using suitable TBI models [230]. Elevation of tumor necrosis factor alpha (TNF-α), elevated c-fos expression, and HSP-72 has been observed in animal fluids post TBI indicating that the expression of these genes has a critical role in TBI, whereas expression of NGF, proteins from Bcl-2 family, and HSP-70 are decreased in TBI or showed features such as promotion of growth, survival, and differentiation of neuronal cells [231]. By the incorporation of viral vectors and certain non-viral vectors to growth factors, there was an attenuation in traumatic injury in focal cortex and these include GDNFadenoviral delivery, gene transfer via AAV8, transfer of calbindin D gene via HSV, NGF expression via transferrinassociated cationic liposome/Tf-lipoplexes.…”

Cell Therapy for CNS Trauma

“…A review of the currently available information on preclinical studies reveals that there are several gene targets with therapeutic potentials and vectors that can be used to deliver the candidate genes [8]. In spite of obstacles in translating these techniques into effective gene therapy in humans, they provide new strategies for neuroprotection in TBI.…”