Regulation of neurotrophins

• US 20070067002A1
• Filed: 12/16/2005
• Published: 03/22/2007
• Est. Priority Date: 04/15/2005
• Status: Active Grant

• Current Assignee: Functional Neuromodulation, Inc. (Functional Neuromodulation, Ltd.)
• Original Assignee: Functional Neuromodulation, Inc. (Functional Neuromodulation, Ltd.)
• Inventors: Lozano, Andres
• Granted Patent: US 8,078,275 B2
• Time in Patent Office: Days
• US Class Current: 607/45
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61N 1/0529 Electrodes for brain stimulation
• CPC Class Codes: A61N 1/0531 Brain cortex electrodes
• CPC Class Codes: A61N 1/0534 Electrodes for deep brain stimulation
• CPC Class Codes: A61N 1/0551 Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: A61N 1/3605 Implantable neurostimulators for stimulating central or peripheral nerve system
• CPC Class Codes: A61N 1/36082 Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
• CPC Class Codes: A61N 1/36121 Production of neurotransmitters; Modulation of genes expression
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

Disclosed are methods for regulating neurotrophin levels within a human body. The invention utilizes an implantable signal generator to deliver stimulation to neural tissue elements. Alternatively, an implantable pump may be utilized to delivery one or more drugs. The implanted device delivers treatment therapy to the neural tissue to thereby alter the level of neurotrophic factors such as BDNF expressed by the influenced neural tissue. A sensor may be used to detect various symptoms of a nervous system disorder. A microprocessor algorithm may then analyze the output from the sensor to regulate the treatment therapy delivered to the body. The invention describes a novel method to regulate the intrinsic levels of neurotrophins and may be used to treat patients with neurological and cognitive disorders.

Claims

1. A method for regulating neurotrophin levels within a human body by means of an implantable signal generator and a lead having a proximal end coupled to the signal generator and a distal portion having at least one electrode, the method comprising:

(A) targeting neural tissue in the body where regulation of a neurotrophin is desired;

(B) implanting at least one electrode so that a stimulation portion lies at least in communication with the targeted neural tissue of the body;

(C) coupling the proximal end of the implanted electrode to the signal generator;

(D) sensing a characteristic indicative of the level of the neurotrophin; and

(E) operating the signal generator to deliver stimulation to the targeted neural tissue to thereby alter the level of the neurotrophin within the body.

2. A method, as claimed in claim 1, wherein (B) comprises implanting the at least one electrode so that the stimulation portion lies at least in communication with a brain element.

3. A method, as claimed in claim 1, wherein (B) comprises implanting the at least one electrode so that the stimulation portion lies at least in communication with a spinal cord.

4. A method, as claimed in claim 1, wherein (B) comprises implanting the at least one electrode so that the stimulation portion lies at least in communication with a peripheral nerve.

5. A method, as claimed in claim 1, wherein (E) comprises selecting amplitude, width and frequency of stimulation by the electrode.

6. A method, as claimed in claim 1, wherein (E) comprises operating the signal generator to pulse at a frequency between 2 Hertz and 1000 Hertz.

7. A method, as claimed in claim 1, wherein (E) comprises operating the signal generator to pulse at a pulse amplitude between 0.1 Volts to 10.0 Volts.

8. A method, as claimed in claim 1, wherein (E) comprises operating the signal generator to pulse at a pulse width between 30 microseconds and 450 microseconds.

9. A method, as claimed in claim 1, wherein (E) comprises operating the signal generator in a monopolar configuration.

10. A method, as claimed in claim 1, wherein (E) comprises operating the signal generator in a bipolar configuration.

11. A method, as claimed in claim 1, wherein (E) comprises operating the signal generator in a multipolar configuration.

12. A method, as claimed in claim 1, wherein (E) comprises operating the signal generator in a continuous mode.

13. A method, as claimed in claim 1, wherein (E) comprises operating the signal generator in a cyclical mode.

14. A method, as claimed in claim 1, further comprising (F) selecting between and open loop and a closed loop mode of operation.

15. A method as claimed in claim 1, further comprising:

(F) generating a sensor signal indicative of the level of the neurotrophin; and

(G) regulating the operation of the signal generator in response to the sensor signal.

16. A method, as claimed in claim 15, wherein (F) comprises detecting the level of neurotrophic factor within the body.

17. A method, as claimed in claim 15, wherein (F) comprises detecting the extent of neuronal loss or damage.

18. A method, as claimed in claim 15, wherein (F) comprises detecting the extent of a neurological disorder.

19. A method as claimed in claim 15, wherein (G) comprises executing a control algorithm.

20. A method, as claimed in claim 15, wherein (G) comprises adjusting at least one parameter of the stimulation, the parameter being selected from the group consisting of amplitude, pulse width and frequency.

21. A method, as claimed in claim 1, further comprising:

(F) implanting at least one secondary electrode so that a secondary stimulation portion lies in communication with a second portion of the body;

(G) coupling the secondary electrode to the signal generator; and

(H) operating the signal generator to stimulate the second portion of the body.

22. A method, as claimed in claim 1, further comprising:

(F) implanting at least one catheter so that a secondary discharge portion lies in communication with second neural tissue elements;

(G) coupling the catheter to a pump; and

(H) operating the pump to deliver drug to the body to thereby alter the level of a neurotrophin generated by the second neural tissue elements.

23. A therapeutic treatment method for regulating neurotrophin levels within a human by means of an implantable pump and at least one catheter having a proximal end coupled to the pump and a discharge portion for infusing therapeutic dosages of at least one drug, the method comprising:

(A) targeting neural tissue in the body where regulation of a neurotrophin is desired;

(B) implanting the catheter so that the discharge portion lies in communication with the targeted neural tissue of the body;

(C) coupling the catheter to the pump;

(D) sensing a characteristic indicative of the level of the neurotrophin; and

(E) operating the pump to deliver the at least one drug to the neural tissue elements to thereby alter the level of the neurotrophin generated by the neural tissue.

24. A method, as claimed in claim 23, wherein (B) comprises implanting the catheter so as to infuse drug in at least a brain element.

25. A method, as claimed in claim 23, wherein (B) comprises implanting the catheter so as to infuse drug in at least a spinal cord.

26. A method, as claimed in claim 23, wherein (B) comprises implanting the catheter so as to infuse drug in at least a peripheral nerve.

27. A method, as claimed in claim 23, wherein (E) comprises selecting a time interval for drug delivery.

28. A method, as claimed in claim 23, wherein (E) comprises selecting a drug dosage.

29. A method as claimed in claim 23, further comprising:

(F) generating a sensor signal indicative of a level of the neurotrophic factor and; and

(G) regulating the operation of the pump in response to the sensor signal.

30. A method, as claimed in claim 29, wherein (F) comprises detecting the level of neurotrophic factor within the body.

31. A method, as claimed in claim 29, wherein (F) comprises detecting the extent of neuronal loss or damage.

32. A method, as claimed in claim 29, wherein (F) comprises detecting the extent of a neurological disorder.

33. A method as claimed in claim 29, wherein (F) comprises executing a control algorithm.

34. A method, as claimed in claim 23, further comprising:

(F) implanting at least one electrode so that a stimulation portion lies in communication with a second neural tissue element;

(G) coupling the secondary electrode to the signal generator; and

(H) operating the signal generator to stimulate the second neural tissue element.

35. A method, as claimed in claim 23, further comprising:

(F) implanting at least one secondary catheter so that a second discharge portion lies in communication with a second portion of the neural tissue;

(G) coupling the catheter to a pump; and

(H) operating the pump to deliver drug to the second portion.

36. A method of using one or more drugs to therapeutically regulate the level of a neurotrophic factor within a human by means of an implantable pump and a catheter having a proximal end coupled to said pump and a discharge portion for infusing therapeutic dosages of said one or more drugs, as well as a signal generator and an implantable electrode having a proximal end and a stimulation portion, the method:

(A) targeting neural tissue elements in the body where regulation of a neurotrophin is desired;

(B) surgically implanting the electrode so that the stimulation portion lies in communication with neural tissue elements within the human;

(C) surgically implanting said catheter so that the discharge portion lies adjacent a predetermined infusion site;

(D) sensing a characteristic indicative of the level of the neurotrophin; and

(E) operating the signal generator to deliver electrical stimulation to the neural tissue elements to thereby alter the level of the neurotrophin within the body; and

(F) operating the pump to discharge a predetermined dosage of at least one drug through the discharge portion of the catheter into the predetermined infusion site to thereby further alter the level of the neurotrophin within the body.