System and method for optogenetic therapy
Configurations are described for utilizing light-activated proteins within cell membranes and subcellular regions to assist with medical treatment paradigms, such as hypertension treatment via anatomically specific and temporally precise modulation of renal plexus activity. The invention provides for proteins, nucleic acids, vectors and methods for genetically targeted expression of light-sensitive proteins to specific cells or defined cell populations. In particular the invention provides systems, devices, and methods for millisecond-timescale temporal control of certain cell activities using moderate light intensities, such as the generation or inhibition of electrical spikes in nerve cells and other excitable cells.
1. A system for creating a directed action potential in a targeted nerve comprising light sensitive protein and coupled to a spinal cord of a patient, comprising:
a. a first implantable optical applicator configured to engage a first portion of the targeted nerve and to deliver light to the targeted nerve, the first implantable optical applicator operatively coupled to a first light source, the first light source configured to deliver photons to the first implantable optical applicator to be emitted by the first implantable optical applicator into the first portion of the targeted nerve to cause a membrane polarization change in the targeted nerve, the delivered photons from the first light source further configured to cause an action potential in the targeted nerve;
b. a second implantable optical applicator configured to engage a second portion of the targeted nerve and to deliver light to the targeted nerve, the second implantable optical applicator operatively coupled to a second light source, the second light source configured to deliver photons to the second implantable optical applicator to be emitted by the second implantable optical applicator into the second portion of the targeted nerve to cause a membrane polarization change in the targeted nerve, the delivered photons from the second light source further configured to inhibit action potential propagation beyond the second implantable optical applicator in a direction defined as proceeding from the first implantable optical applicator toward the second implantable optical applicator; and
c. a controller operatively coupled to the first light source and the second light source and configured to cause photons to be directed to each of the first and second implantable optical applicators, such that an action potential is created which propagates in a single desired direction along the nerve beyond the second implantable optical applicator.
2. The system of claim 1 , wherein the first implantable optical applicator and second implantable optical applicator are serially coupled to the nerve with the first implantable optical applicator positioned closer to the spinal cord than the second implantable optical applicator.
3. The system of claim 2 , wherein the nerve has been genetically modified to encode an opsin protein.
4. The system of claim 3 , wherein the opsin protein is a stimulatory opsin protein.
5. The system of claim 3 , wherein the opsin protein is an inhibitory opsin protein.
6. The system of claim 5 , wherein the inhibitory opsin protein is selected from the group consisting of: NpHR, eNpHR 1.0, eNpHR 2.0, eNpHR 3.0, Mac, Mac 3.0, Arch, and ArchT.
7. The system of claim 5 , wherein the stimulatory opsin protein is selected from the group consisting of: ChR2, C1V1-T, C1V1-TT, CatCh, VChR1-SFO, and ChR2-SFO.
8. The system of claim 7 , wherein the controller is configured to cause the second light source to create a hyperstimulation block away from the spinal cord with the second implantable optical applicator, while also causing the first light source to create an action potential with the first implantable optical applicator directed in the opposite direction toward the spinal cord.
9. The system of claim 7 , wherein the controller is configured to cause the first light source to create a hyperstimulation block toward the spinal cord with the first implantable optical applicator, while also causing the second light source to create an action potential with the second implantable optical applicator directed in the opposite direction away from the spinal cord.
10. The system of claim 5 , wherein the nerve has been further genetically modified to encode a second opsin protein that is a stimulatory opsin protein.
11. The system of claim 10 , wherein the controller is configured to cause the first light source to create an action potential directed toward the spinal cord by stimulating with light having a wavelength selected to activate the stimulatory opsin protein, and wherein the controller is configured to cause the second light source to inhibit action potentials in the direction away from the spinal cord by stimulating with light having a wavelength selected to activate the inhibitory opsin protein.
12. The system of claim 10 , wherein the controller is configured to cause the second light source to create an action potential directed away from the spinal cord by stimulating with light having a wavelength selected to activate the stimulatory opsin protein, and wherein the controller is configured to cause the first light source to inhibit action potentials in the direction toward the spinal cord by stimulating with light having a wavelength selected to activate the inhibitory opsin protein.
13. The system of claim 10 , wherein the inhibitory opsin protein is selected from the group consisting of: NpHR, eNpHR 1.0, eNpHR 2.0, eNpHR 3.0, Mac, Mac 3.0, Arch, and ArchT.
14. The system of claim 10 , wherein the stimulatory opsin protein is selected from the group consisting of: ChR2, C1V1-T, C1V1-TT, CatCh, VChR1-SFO, and ChR2-SFO.