Methods and systems for neural maintenance and regeneration

• US 20060282062A1
• Filed: 06/10/2005
• Published: 12/14/2006
• Est. Priority Date: 06/10/2005
• Status: Active Grant

• Current Assignee: Gearbox LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Ishikawa, Muriel Y., Wood, Lowell L. Jr., Jung, Edward K.Y.
• Granted Patent: US 8,309,057 B2
• Time in Patent Office: Days
• US Class Current: 604/890.100
• CPC Class Codes: A61F 11/00 Methods or devices for treatment of the ears or hearing sense implantable prostheses that substitute or replace internal ear parts, e.g. ear-drums, A61F2/18; methods or devices to cause a change in the state of auditory consciousness A61M21/00; electrotherapy applying electrical stimulation of the auditory system, or circuits therefor A61N1/36; radiotherapy using optical stimulation of the auditory system A61N5/06; electro-acoustic hearing aids H04R25/00; Non-electric hearing aids; Methods or devices for enabling ear patients to achieve auditory perception through physiological senses other than hearing sense; Protective devices for the ears, carried on the body or in the hand headwear, e.g. caps or helmets, with means for protecting the ears A42B1/0188, A42B3/16
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61M 2005/1726 the body parameters being measured at, or proximate to, the infusion site
• CPC Class Codes: A61M 2210/0612 Eyes
• CPC Class Codes: A61M 2210/0618 Nose
• CPC Class Codes: A61M 2210/0643 Tongue
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses

Abstract

Methods and systems are described that release one or both of a neurotrophin and an inhibitor of the degradation of the neurotrophin within or in the vicinity of a highly innervated tissue. In some embodiments, the method includes regulating the release of the neurotrophin and the inhibitor of degradation over time. In some embodiments, the method includes monitoring the concentration of the neurotrophin over time. The system may include a device or multiple devices for the release of the neurotrophin and the inhibitor as well as a controller. In some embodiments the system may include a sensor device and/or an imaging device capable of detecting the concentration of the neurotrophin over time. The release of the neurotrophin and inhibitor of degradation may be part of a controlled release system and regulated over time.

Claims

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13. A system comprising:

a neurotrophin release device capable of releasing at least one neurotrophin;

an inhibitor release device capable of releasing at least one inhibitor of degradation of the neurotrophin;

a controller capable of regulating the release of at least one of the neurotrophin and the inhibitor of degradation; and

a connection between the controller and at least one of said neurotrophin release device and said inhibitor release device.

14. The system of claim 13, wherein the controller generates at least one control signal that is transmitted to at least one of said neurotrophin release device and said inhibitor release device via said connection.

16. The system of claim 13 wherein said neurotrophin release device comprises a reservoir of said neurotrophin.

17. The system of claim 13 wherein said inhibitor release device comprises a reservoir of said inhibitor.

18. The system of claim 13, wherein said neurotrophin release device and said inhibitor release device are implantable within the body of a mammal.

25. The system of claim 13, further comprising a sensor capable of sensing the concentration of the neurotrophin.

27. The system of claim 25, further comprising an imaging device adapted to receive information from the sensor and capable of displaying the information from the sensor.

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28. A method comprising:

elevating the concentration of at least one neurotrophin within highly innervated tissue in a subject; and

elevating the concentration of at least one inhibitor of degradation of said neurotrophin within the highly innervated tissue.

29. The method as in claim 28 wherein the subject is a human.

43. The method as in claim 28 wherein the highly innervated tissue is part of the central nervous system.

44. The method as in claim 28 wherein the highly innervated tissue is part of the peripheral nervous system.

49. The method as in claim 28, further comprising:

regulating the concentration of the neurotrophin over time.

50. The method as in claim 28, further comprising:

regulating the concentration of said at least one inhibitor of degradation of the neurotrophin over time.

52. The method as in claim 28, further comprising:

monitoring the concentration of the neurotrophin within the innervated tissue.

53. The method as in claim 28 wherein the neurotrophin is adenosine 3′

, 5′

-cyclic monophosphate (cAMP).

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54. A method comprising:

elevating the level of a neurotrophin within a sensory organ of a mammal;

elevating the level of at least one inhibitor of degradation of said neurotrophin within said sensory organ; and

controlling the levels of said neurotrophin over time.

55. The method as in claim 54, further comprising:

monitoring the level of said neurotrophin within the sensory organ.

56. The method as in claim 54, further comprising:

elevating the level of neurotrophin to a predetermined level.

57. The method as in claim 54, further comprising:

determining a target level of neurotrophin in the sensory organ and

elevating the level of neurotrophin to the target level.

60. The method as in claim 54, further comprising:

controlling the levels of said at least one inhibitor of the degradation of said neurotrophin over time.

61. The method of claim 60, wherein the control of the level of said at least one inhibitor of the degradation of said neurotrophin is a function of the level of said neurotrophin over time.

67. The method as in claim 54, wherein the mammal is a human.

69. The method as in claim 54, wherein the sensory organ is auditory, olfactory, visual, or somatosensory.

70. The method as in claim 54, wherein the sensory organ is the cochlea, the olfactory bulb or the retina.

72. The method as in claim 54, further comprising;

releasing a neural support substance.

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85. A method of controlling the concentration of a neurotrophin, comprising:

a. Detecting the concentration of the neurotrophin in a region of a nervous system of a subject;

b. Calculating a quantity of a composition to be released in said region, wherein said composition being of a type that has been selected to modulate the concentration of said neurotrophin within said region, and wherein said calculated quantity is sufficient to adjust said detected concentration toward a target concentration of said neurotrophin;

c. Releasing said quantity of said composition in said region; and

d. Repeating steps a through c to provide ongoing control of the concentration of said neurotrophin.

86. The method of claim 85, wherein said composition comprises said neurotrophin.

87. The method of claim 85, wherein said composition comprises an inhibitor of degradation of said neurotrophin.

89. The method of claim 85, wherein said composition comprises said neurotrophin and at least one additional neurotrophin.

91. The method of claim 85, where said composition comprises a neurotrophin, and at least one of a second neurotrophin, an inhibitor of degradation of said neurotrophin, and a neural support substance.

92. The method of claim 85, wherein said quantity of said composition is released within a sensory organ.

98. The method of claim 85, wherein said calculating step is performed by a processor, wherein said detected concentration is provided to said processor as a feedback signal, wherein said processor generates a control signal representing said quantity of said composition, and wherein said control signal controls said releasing of said quantity of said composition.

99. The method of claim 85, wherein said quantity of said composition is released over a predetermined time interval to provide a controlled rate of release of said composition.

102. The method of claim 85, wherein said target concentration comprises a predetermined sequence of target values.

103. The method of claim 102, wherein said predetermined sequence of target values are a cyclic sequence.

104. The method of claim 85, wherein said target concentration is calculated as a function of said detected concentration.

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106. A system for modulating the concentration of a neurotrophin comprising:

a. A sensor capable of detecting the concentration of the neurotrophin in a region of a nervous system of a subject;

b. A memory device capable of storing a target concentration;

c. A processor capable of comparing said detected concentration with said target concentration to compute a quantity of a composition to be released to adjust said detected concentration toward said target concentration;

d. A control signal generator capable of generating a control signal representing said computed quantity; and

e. A controlled release device controllable by said control signal to release said composition in the vicinity of said sensory organ.

107. The system of claim 106, wherein said computed quantity is to be released over a fixed time interval so that said controlled release device controls a rate of release of said composition.

108. The system of claim 106, wherein said controlled release device further comprises a reservoir containing said composition.

109. The system of claim 106, wherein said composition comprises said neurotrophin.

111. The system of claim 106, wherein said composition comprises an inhibitor of degradation of said neurotrophin.

114. The system of claim 106 wherein said composition comprises a neural support substance.

115. The system of claim 106, wherein said neurotrophin is cAMP.

118. The system of claim 106, wherein said region of the nervous system is a sensory organ.

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