System and method for optogenetic therapy

• US 9,821,170 B2
• Filed: 07/28/2014
• Issued: 11/21/2017
• Est. Priority Date: 11/21/2012
• Status: Active Grant

• Current Assignee: Circuit Therapeutics, Inc.
• Original Assignee: Circuit Therapeutics, Inc.
• Inventors: Lundmark, David C., Deisseroth, Karl, Moll, Fred, Andersen, Dan, Arrow, Alexander K.
• Primary Examiner(s): FARAH, AHMED M
• Application Number:
  US14/444,722
• Publication Number:
  US 20160051836A1
• Time in Patent Office: 1,212 Days
• Field of Search: 607 88, 607 89, 607 91, 607 92, 128898
• 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 preventing hypertension in a patient, comprising:

a. an implantable optical applicator configured to be permanently coupled to at least one tissue structure such that it can deliver photons to at least one branch of the renal nerve plexus that has been genetically modified to have light sensitive protein;

b. an implantable light source and an implantable power supply, the implantable light source being operatively intercoupled between the implantable power supply and the implantable optical applicator such that photons generated when the implantable light source is drawing current from the implantable power supply may be delivered to the implantable optical applicator;

c. an implantable sensor configured to be deployed within the body of the patient and to provide an output signal that is correlated with the blood pressure of the patient; and

d. an implantable controller operatively coupled to the implantable sensor and implantable light source, the implantable controller configured to cause the implantable light source to illuminate the light sensitive protein through the implantable light source and implantable optical applicator to at least partially inhibit action potential transmission within the at least one branch of the renal nerve plexus based at least in part upon the output signal received from the implantable sensor.

2. The system of claim 1, wherein the implantable optical applicator is configured to be permanently coupled around a renal artery of the patient.

3. The system of claim 2, wherein the implantable optical applicator comprises a cuff configured to at least partially circumferentially surround a portion of the renal artery with intercoupled renal nerve plexus branches.

4. The system of claim 2, wherein the implantable optical applicator comprises a slab-type applicator that may be rolled to at least partially circumferentially surround a portion of the renal artery with intercoupled renal nerve plexus branches.

5. The system of claim 4, wherein the slab-type applicator is rolled axially to improve engagement of the portion of the renal artery with intercoupled renal nerve plexus branches.

6. The system of claim 4, wherein the slab-type applicator is rolled longitudinally to improve engagement of the portion of the renal artery with intercoupled renal nerve plexus branches.

7. The system of claim 2, wherein the implantable optical applicator comprises a helical-type waveguide positioned around the portion of the renal artery with intercoupled renal nerve plexus branches, the helical-type waveguide configured to output couple light inward toward a central longitudinal axis of the helical-type waveguide such that the outcoupled light encounters the portion of the renal artery with intercoupled renal nerve plexus branches.

8. The system of claim 1, further comprising an external controller configured to wirelessly communicate with the implantable controller.

9. The system of claim 2, wherein the implantable light source is immediately coupled to the implantable optical applicator, and wherein the implantable light source is operatively coupled to the implantable power supply and implantable controller, such that the implantable controller activates the implantable light source by controlling current thereto from the implantable power supply.

10. The system of claim 9, wherein the implantable light source is operatively coupled to the implantable power supply and controller with a delivery segment configured to carry electrical current.

11. The system of claim 9, wherein the implantable power supply is coupled to one or more implantable inductive coils configured to receive magnetic flux from a transcutaneous magnetic flux source configured to recharge the implantable power supply.

12. The system of claim 11, further comprising a transcutaneous magnetic flux source configured to be positioned in a charging position near the skin adjacent the one or more implantable inductive coils.

13. The system of claim 12, wherein the transcutaneous magnetic flux source is coupled to a mounting device configured to retain the transcutaneous magnetic flux source in the charging position for a period of time while the patient is active.

14. The system of claim 9, wherein the implantable power supply and implantable controller are housed within a common implantable housing.

15. The system of claim 9, wherein the light source comprises a light emitting diode.

16. The system of claim 9, wherein the tissue structure comprising the light sensitive protein has been genetically modified to encode an opsin protein.

17. The system of claim 16, wherein the opsin protein is an inhibitory opsin protein.

18. The system of claim 17, 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.

19. The system of claim 16, wherein the opsin protein is a stimulatory opsin protein.

20. The system of claim 17, wherein the stimulatory opsin protein is selected from the group consisting of:

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

21. The system of claim 9, wherein the light source is pulsed with a pulse duration between about 0.1 and about 20 milliseconds, using a duty cycle between about 0.1 and 100 percent.

22. The system of claim 9, wherein the implantable light source is operated to use the implantable optical applicator to direct photons at the at least one tissue structure with a surface irradiance of between about 5 milliwatts per square millimeter to about 200 milliwatts per square millimeter.

23. The system of claim 2, further comprising a delivery segment intercoupled between the implantable light source and the implantable optical applicator, the delivery segment configured to propagate light from the implantable light source to the implantable optical applicator.

24. The system of claim 23, wherein the delivery segment comprises a waveguide configured to propagate substantially all light that is passed through it via total internal reflection.

25. The system of claim 23, wherein the implantable light source, implantable power supply, and implantable controller are housed within a common implantable housing.

26. The system of claim 23, wherein the implantable light source comprises a light emitting diode.

27. The system of claim 23, wherein the implantable power supply is coupled to one or more implantable inductive coils configured to receive magnetic flux from a transcutaneous magnetic flux source configured to recharge the implantable power supply.

28. The system of claim 27, further comprising a transcutaneous magnetic flux source configured to be positioned in a charging position near the skin adjacent the one or more implantable inductive coils.

29. The system of claim 28, wherein the transcutaneous magnetic flux source is coupled to a mounting device configured to retain the transcutaneous magnetic flux source in the charging position for a period of time while the patient is active.

30. The system of claim 23, wherein the tissue structure comprising the light sensitive protein has been genetically modified to encode an opsin protein.

31. The system of claim 30, wherein the opsin protein is an inhibitory opsin protein.

32. The system of claim 31, 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.

33. The system of claim 30, wherein the opsin protein is a stimulatory opsin protein.

34. The system of claim 31, wherein the stimulatory opsin protein is selected from the group consisting of:

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

35. The system of claim 23, wherein the light source is pulsed with a pulse duration between about 0.1 and about 20 milliseconds, using a duty cycle between about 0.1 and 100 percent.

36. The system of claim 23, wherein the implantable light source is operated to use the implantable optical applicator to direct photons at the at least one tissue structure with a surface irradiance of between about 5 milliwatts per square millimeter to about 200 milliwatts per square millimeter.

37. The system of claim 1, wherein the implantable optical applicator is configured to be permanently coupled around a RENAL PELVIS of the patient.

38. The system of claim 37, wherein the implantable optical applicator comprises a cuff configured to at least partially circumferentially encapsulate a portion of the renal pelvis with intercoupled renal nerve plexus branches.

39. The system of claim 37, wherein the implantable optical applicator comprises a slab-type applicator that may be rolled to at least partially circumferentially encapsulate a portion of the renal pelvis with intercoupled renal nerve plexus branches.

40. The system of claim 39, wherein the slab-type applicator is rolled axially to improve engagement of the portion of the renal artery with intercoupled renal nerve plexus branches.

41. The system of claim 39, wherein the slab-type applicator is rolled longitudinally to improve engagement of the portion of the renal artery with intercoupled renal nerve plexus branches.

42. The system of claim 37, wherein the implantable optical element comprises a web-like compliant substrate.

43. The system of claim 37, wherein the implantable light source is immediately coupled to the implantable optical applicator, and wherein the implantable light source is operatively coupled to the implantable power supply and implantable controller, such that the implantable controller activates the implantable light source by controlling current thereto from the implantable power supply.

44. The system of claim 43, wherein the implantable light source is operatively coupled to the implantable power supply and controller with a delivery segment configured to carry electrical current.

45. The system of claim 43, wherein the implantable power supply is coupled to one or more implantable inductive coils configured to receive magnetic flux from a transcutaneous magnetic flux source configured to recharge the implantable power supply.

46. The system of claim 45, further comprising a transcutaneous magnetic flux source configured to be positioned in a charging position near the skin adjacent the one or more implantable inductive coils.

47. The system of claim 46, wherein the transcutaneous magnetic flux source is coupled to a mounting device configured to retain the transcutaneous magnetic flux source in the charging position for a period of time while the patient is active.

48. The system of claim 43, wherein the implantable power supply and implantable controller are housed within a common implantable housing.

49. The system of claim 43, wherein the light source comprises a light emitting diode.

50. The system of claim 43, wherein the tissue structure comprising the light sensitive protein has been genetically modified to encode an opsin protein.

51. The system of claim 50, wherein the opsin protein is an inhibitory opsin protein.

52. The system of claim 51, 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.

53. The system of claim 50, wherein the opsin protein is a stimulatory opsin protein.

54. The system of claim 51, wherein the stimulatory opsin protein is selected from the group consisting of:

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

55. The system of claim 43, wherein the light source is pulsed with a pulse duration between about 0.1 and about 20 milliseconds, using a duty cycle between about 0.1 and 100 percent.

56. The system of claim 43, wherein the implantable light source is operated to use the implantable optical applicator to direct photons at the at least one tissue structure with a surface irradiance of between about 5 milliwatts per square millimeter to about 200 milliwatts per square millimeter.

57. The system of claim 37, further comprising a delivery segment intercoupled between the implantable light source and the implantable optical applicator, the delivery segment configured to propagate light from the implantable light source to the implantable optical applicator.

58. The system of claim 57, wherein the delivery segment comprises a waveguide configured to propagate substantially all light that is passed through it via total internal reflection.

59. The system of claim 57, wherein the implantable light source, implantable power supply, and implantable controller are housed within a common implantable housing.

60. The system of claim 57, wherein the implantable light source comprises a light emitting diode.

61. The system of claim 57, wherein the implantable power supply is coupled to one or more implantable inductive coils configured to receive magnetic flux from a transcutaneous magnetic flux source configured to recharge the implantable power supply.

62. The system of claim 61, further comprising a transcutaneous magnetic flux source configured to be positioned in a charging position near the skin adjacent the one or more implantable inductive coils.

63. The system of claim 62, wherein the transcutaneous magnetic flux source is coupled to a mounting device configured to retain the transcutaneous magnetic flux source in the charging position for a period of time while the patient is active.

64. The system of claim 57, wherein the tissue structure comprising the light sensitive protein has been genetically modified to encode an opsin protein.

65. The system of claim 64, wherein the opsin protein is an inhibitory opsin protein.

66. The system of claim 65, 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.

67. The system of claim 64, wherein the opsin protein is a stimulatory opsin protein.

68. The system of claim 65, wherein the stimulatory opsin protein is selected from the group consisting of:

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

69. The system of claim 57, wherein the light source is pulsed with a pulse duration between about 0.1 and about 20 milliseconds, using a duty cycle between about 0.1 and 100 percent.

70. The system of claim 57, wherein the implantable light source is operated to use the implantable optical applicator to direct photons at the at least one tissue structure with a surface irradiance of between about 5 milliwatts per square millimeter to about 200 milliwatts per square millimeter.

71. The system of claim 1, wherein the implantable sensor comprises a sensing element selected from the group consisting of:

a diaphragm, a piston, a bourdon tube, a bellows, and a strain gauge.

72. The system of claim 1, wherein the implantable sensor output signal is produced by a transducer selected from the group consisting of:

a piezoelectric transducer, a capacitive transducer, an electromagnetic transducer, an optical transducer, and a resonant transducer.

73. The system of claim 1, wherein the implantable sensor is operatively coupled to the implantable controller via a physically wired connection.

74. The system of claim 1, wherein the implantable sensor is operatively coupled to the implantable controller via a wireless connection.

75. The system of claim 1, wherein the implantable sensor is deployed to monitor the pressure within an arterial vessel selected from the group consisting of:

a femoral artery, a brachial artery, a carotid artery, an aorta, a renal artery, an iliac artery, a subclavian artery, and an axillary artery.

76. The system of claim 1, wherein the implantable sensor is coupled to a coupling device configured to maintain the position of the implantable sensor relative to a nearby pressurized vessel.

77. The system of claim 76, wherein the coupling device comprises an implantable cuff configured to extend circumferentially around a pressurized blood vessel.

78. The system of claim 1, wherein the implantable optical applicator is configured to be endoluminally delivered through the urethra, bladder, and ureter of the patient and implanted inside of the renal pelvis of the kidney of the patient.

79. The system of claim 78, further comprising an expandable coupling device coupled to the implantable optical applicator and configured to be delivered through a catheter in a compressed form to the renal pelvis, after which it may be converted to an expanded form to mechanically couple the inside of the renal pelvis.

80. The system of claim 79, wherein the expandable coupling device comprises a stent.

81. The system of claim 78, wherein the implantable light source is immediately coupled to the implantable optical applicator, and wherein the implantable light source is operatively coupled to the implantable power supply and implantable controller, such that the implantable controller activates the implantable light source by controlling current thereto from the implantable power supply.

82. The system of claim 81, wherein the implantable controller and implantable power supply are located outside of the bounds of the urinary tract, and wherein a delivery segment is routed across a wall of the urinary tract of the patient to carry current to the implantable optical applicator.

83. The system of claim 78, further comprising a delivery segment intercoupled between the implantable light source and the implantable optical applicator, the delivery segment configured to propagate light from the implantable light source to the implantable optical applicator.

84. The system of claim 83, wherein the implantable controller, implantable power supply, and implantable light source are located outside of the bounds of the urinary tract, and wherein the delivery segment is routed across a wall of the urinary tract of the patient to carry light to the implantable optical applicator.

85. The system of claim 83, wherein wherein the delivery segment comprises a waveguide configured to propagate substantially all light that is passed through it via total internal reflection.

86. The system of claim 83, wherein the implantable light source, implantable power supply, and implantable controller are housed within a common implantable housing.