System and method for optogenetic therapy

• US 9,649,503 B2
• Filed: 07/28/2014
• Issued: 05/16/2017
• Est. Priority Date: 11/21/2012
• Status: Expired due to Fees

• Current Assignee: Circuit Therapeutics, Inc.
• Original Assignee: Circuit Therapeutics, Inc.
• Inventors: Delp, Scott, Deisseroth, Karl, Andersen, Dan
• Primary Examiner(s): Wieland, Robert N
• Application Number:
  US14/444,894
• Publication Number:
  US 20160045764A1
• Time in Patent Office: 1,023 Days
• CPC Class Codes: A61B 17/00234 for minimally invasive surgery A61B17/0218, A61B17/0469, A61B17/12013, A61B17/1285, A61B17/29, A61B17/320016 take precedence
• CPC Class Codes: A61B 17/3403 Needle locating or guiding means guides for suture needles A61B17/0482; guiding or tracking by nuclear magnetic resonance G01R33/285
• CPC Class Codes: A61B 2017/3413 guided by ultrasound
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/164 from bacteria
• CPC Class Codes: A61K 38/168 from plants
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2205/3576 with non implanted data transmission devices, e.g. using external transmitter or receiver
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 25/0105 Steering means as part of the catheter or advancing means; Markers for positioning systems for detection of markers A61B
• CPC Class Codes: A61M 25/0147 with movable mechanical means, e.g. pull wires
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 5/142 Pressure infusion, e.g. using pumps
• CPC Class Codes: A61M 5/20 Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically A61M5/142 , A61M5/46 take precedence; hypodermic projectiles F42B12/54
• CPC Class Codes: A61N 1/0551 : Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/3605 : Implantable neurostimulators for stimulating central or peripheral nerve system
• CPC Class Codes: A61N 1/36053 : adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 2005/0612 : using probes penetrating tissue; interstitial probes
• CPC Class Codes: A61N 2005/0626 : Monitoring, verifying, controlling systems and methods
• CPC Class Codes: A61N 2005/0627 : Dose monitoring systems and methods
• CPC Class Codes: A61N 2005/063 : comprising light transmitting means, e.g. optical fibres
• CPC Class Codes: A61N 2005/0631 : using crystals
• CPC Class Codes: A61N 2005/0643 : Applicators, probes irradiating specific body areas in close proximity
• CPC Class Codes: A61N 2005/0651 : Diodes
• CPC Class Codes: A61N 2005/0653 : Organic light emitting diodes
• CPC Class Codes: A61N 2005/0665 : Reflectors
• CPC Class Codes: A61N 5/0601 : Apparatus for use inside the body
• CPC Class Codes: A61N 5/062 : Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61N 5/0622 : Optical stimulation for exciting neural tissue
• CPC Class Codes: A61N 5/067 : using laser light
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

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.

Claims

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 light source;

b. an implantable optical applicator configured to engage the targeted nerve and to deliver light to the targeted nerve, the implantable optical applicator operatively coupled to the light source and configured to deliver photons to the implantable optical applicator which may be emitted by the implantable optical applicator into the targeted nerve to cause a membrane polarization change in the targeted nerve;

c. a power source;

d. an implantable electrical stimulation applicator configured to engage the targeted nerve, the implantable electrical stimulation applicator operatively coupled to the power source and configured to deliver electrons to the implantable electrical stimulation applicator which may be emitted by the implantable electrical stimulation applicator into the targeted nerve to cause a membrane polarization change in the targeted nerve; and

e. a controller operatively coupled to the light source and the power source and configured to cause both current to flow to the implantable electrical stimulation applicator and photons to be directed to the implantable optical applicator, such that an action potential is created which propagates in a first desired direction along the nerve, and which does not substantially propagate in a reverse direction along the nerve.

2. The system of claim 1, wherein the implantable optical applicator and implantable electrical applicator are serially coupled to the nerve with the implantable optical applicator positioned closer to the spinal cord than the implantable electrical 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 an inhibitory opsin protein.

5. The system of claim 4, 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.

6. The system of claim 3, wherein the opsin protein is a stimulatory opsin protein.

7. The system of claim 4, 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 light source to create an action potential directed toward the spinal cord, while also causing the power source to hyperstimulate the implantable electrical applicator to cause inhibition of an action potential in the opposite direction away from the spinal cord.

9. The system of claim 7, wherein the controller is configured to cause the light source to create a hyperstimulation block toward the spinal cord, while also causing the power source to stimulate the implantable electrical applicator to create an action potential directed in the opposite direction away from the spinal cord.

10. The system of claim 4, wherein the controller is configured to cause the light source to inhibit action potentials toward the spinal cord, while also causing the power source to stimulate the implantable electrical applicator to create an action potential directed in the opposite direction away from the spinal cord.

11. The system of claim 1, wherein the implantable optical applicator and implantable electrical applicator are serially coupled to the nerve with the implantable electrical applicator positioned closer to the spinal cord than the implantable optical applicator.

12. The system of claim 11, wherein the nerve has been genetically modified to encode an opsin protein.

13. The system of claim 12, wherein the opsin protein is an inhibitory opsin protein.

14. The system of claim 13, 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.

15. The system of claim 12, wherein the opsin protein is a stimulatory opsin protein.

16. The system of claim 13, wherein the stimulatory opsin protein is selected from the group consisting of:

ChR2, C1V1-T, C1V1-TT, CatCh, VChR1-SFO, and ChR2-SFO.

17. The system of claim 16, wherein the controller is configured to cause the light source to create an action potential directed away from the spinal cord, while also causing the power source to hyperstimulate the implantable electrical applicator to cause inhibition of an action potential in the opposite direction toward the spinal cord.

18. The system of claim 16, wherein the controller is configured to cause the light source to create a hyperstimulation block away from the spinal cord, while also causing the power source to stimulate the implantable electrical applicator to create an action potential directed in the opposite direction toward the spinal cord.

19. The system of claim 13, wherein the controller is configured to cause the light source to inhibit action potentials away from the spinal cord, while also causing the power source to stimulate the implantable electrical applicator to create an action potential directed in the opposite direction toward the spinal cord.