Effective neuropathic pain relief through sciatic nerve administration of GAD65-expressing rAAV2.
Recently, we demonstrated that the administration of GAD65-expressing rAAV2 to DRG attenuates peripheral neuropathy by inducing GABA release in the spinal cord. However, the direct injection to DRG is invasive and may therefore cause nerve injury and other side effects. To circumvent this surgical intervention, we explored the potential of a much simpler and less invasive route of sciatic nerve administration. Using a neuropathic pain model, we introduced rAAV2-GAD65 through sciatic nerve and examined its therapeutic potency in pain-related behavior tests. Both GFP and GAD65 expression indicated that effective transgene delivery to the DRG can be accomplished via sciatic nerve administration. Equally importantly, the GABA concentration in the spinal cord increased significantly after GAD65 introduction, and pain symptoms were dramatically reduced and persistently controlled. The implication is that the sciatic nerve is a highly promising route for delivering rAAV2 to the DRG, and thus represents a much less invasive, clinically viable gene therapy option.
Kim
Jaehyung
J
Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
Kim
Sung Jin
SJ
Lee
Heuiran
H
Chang
Jin Woo
JW
D000256:Adenoviridae; D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005968:Glutamate Decarboxylase / Q000235:genetics*; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000628:therapy*; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve
D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2