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Viral-Mediated Optogenetic Stimulation of Peripheral Motor Nerves in Non-human Primates
Jordan J Williams1, Alan M Watson2,3, Alberto L Vazquez4,5
1Department of Neurobiology, Systems Neuroscience Institute, University of Pittsburgh, Pittsburgh, PA, United States.
Frontiers in Neuroscience
|August 17, 2019
Summary
Optogenetic stimulation of peripheral nerves using gene therapy in non-human primates successfully reanimates paralyzed muscles. This study demonstrates the feasibility of optogenetics for future clinical applications in neuroprosthetics.
Area of Science:
- Neuroscience
- Gene Therapy
- Biomedical Engineering
Background:
- Muscle paralysis from spinal cord injury presents a significant therapeutic challenge.
- Optogenetics offers a promising alternative to functional electrical stimulation (FES) for muscle reanimation.
- Translating optogenetic techniques to clinical practice requires successful demonstration in non-human primates.
Purpose of the Study:
- To assess the feasibility of optogenetic stimulation of peripheral motor nerves in non-human primates.
- To evaluate the functional expression of opsins (ChR2 and Chronos) following viral gene delivery.
- To characterize electromyographic (EMG) responses to optical nerve stimulation.
Main Methods:
- Three rhesus macaques received intramuscular injections of optogenetic constructs (AAV6-hSyn-ChR2-eYFP and/or AAV6-hSyn-Chronos-eYFP).
- Virus delivery to neuromuscular junctions was facilitated by electrical stimulation.
- Functional opsin expression was assessed via optical nerve stimulation and EMG recordings up to 13 weeks post-injection.
Main Results:
- Functional opsin expression and optically stimulated muscle contractions were observed in two of three monkeys.
- EMG responses demonstrated graded recruitment with varying stimulus parameters and sustained activity up to 16 Hz.
- A variable timeline of functional opsin expression was noted, ranging from 5.5 to 10 weeks.
Conclusions:
- Viral gene therapy enables optogenetic control of motor activity in non-human primates.
- These findings represent a critical step towards clinical translation of optogenetics for muscle reanimation.
- The study highlights the potential of optogenetics as a viable gene therapy for neurological disorders.
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