Method and apparatus for device controlled gene expression for cardiac protection

• US 8,538,520 B2
• Filed: 07/06/2010
• Issued: 09/17/2013
• Est. Priority Date: 09/06/2005
• Status: Expired due to Fees

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Pastore, Joseph M., Ross, Jeffrey, Baynham, Tamara Colette, Salo, Rodney W., Kramer, Andrew P., Spinelli, Julio C.
• Primary Examiner(s): Layno, Carl H
• Assistant Examiner(s): BEHRINGER, LUTHER G
• Application Number:
  US12/830,534
• Publication Number:
  US 20100274306A1
• Time in Patent Office: 1,169 Days
• Field of Search: 607/2
• US Class Current: 607/9
• CPC Class Codes: A61K 48/0083 characterised by an aspect of the administration regime
• CPC Class Codes: A61N 1/3627 for treating a mechanical deficiency of the heart, e.g. congestive heart failure or cardiomyopathy
• CPC Class Codes: A61N 1/36514 controlled by a physiological quantity other than heart potential, e.g. blood pressure controlled by two or more physical parameters A61N1/36585

Abstract

A gene regulatory system detects ischemia events and is capable of delivering a biologic therapy in response to the detection of an ischemic event or the reception of a command. The biologic therapy protects the heart from ischemic damage by regulating the expression of an exogenously introduced gene product. In one embodiment, the gene regulatory system includes an implantable system that emits at least one gene regulatory signal in response to the detection of the ischemic event or the reception of the command. The gene regulatory signal directly or indirectly regulates gene expression of the gene product.

Claims

1. A method for cardiac protection, the method comprising:

sensing one or more parameters indicative of an ischemic event in a mammal using an implantable medical device;

detecting the ischemic event from the one or more parameters, including detecting an end of the ischemic event, using the implantable medical device;

initiating one or more cardiac protection biologic therapies using the implantable medical device in response to the detection of the ischemic event, the one or more cardiac protection biologic therapies each including at least one signaling and non-signaling period, the at least one signaling period having a signaling duration during which at least one gene regulatory signal is delivered, the at least one non-signaling period having a non-signaling duration during which the at least one gene regulatory signal is not delivered, the at least one gene regulatory signal is capable of directly or indirectly regulating a regulatable transcriptional control element without inducing cardiac depolarization, the regulatable transcriptional control element is operably linked to an open reading frame forming an expression cassette, wherein the expression cassette is present in the mammal, and wherein expression of the open reading frame in an effective amount inhibits damage to tissue in the mammal resulting from ischemia; and

delivering the at least one gene regulatory signal from the implantable medical device during at least one of the signaling periods,

wherein the one or more cardiac protection biologic therapies include at least one postconditioning cardiac biologic therapy, and initiating the one or more cardiac protection biologic therapies includes initiating the at least one postconditioning cardiac biologic therapy using the implantable medical device when a post-ischemia time interval expires, the post-ischemia time interval starting at the detected end of the ischemic event and ending after a predicted reperfusion period following the ischemic event has started.

2. The method of claim 1, wherein the post-ischemia time interval is up to approximately 10 minutes.

3. The method of claim 1, further comprising timing the at least one postconditioning cardiac biologic therapy including alternating postconditioning signaling and non-signaling periods, the at least one postconditioning cardiac biologic therapy having a postconditioning therapy duration in a range of approximately 30 seconds to 1 hour, the postconditioning signaling period having a postconditioning signal duration in a range of approximately 5 seconds to 10 minutes during which the at least one gene regulatory signal is delivered, the postconditioning non-signaling period having a postconditioning non-signal duration in a range of approximately 5 seconds to 10 minutes during which the at least one gene regulatory signal is not delivered.

4. The method of claim 1, wherein the one or more cardiac protection biologic therapies further comprise a plurality of preconditioning cardiac biologic therapies, and further comprising initiating the preconditioning cardiac biologic therapies after the postconditioning cardiac biologic therapy is completed.

5. The method of claim 4, wherein initiating the preconditioning cardiac biologic therapies comprises initiating the preconditioning cardiac biologic therapies on a periodic basis using a predetermined period in a range of approximately 24 hours to 72 hours.

6. The method of claim 4, wherein initiating the preconditioning cardiac biologic therapies comprises initiating the preconditioning cardiac biologic therapies in response to one or more preconditioning commands.

7. The method of claim 4, further comprising timing the plurality of preconditioning cardiac biologic therapies each including alternating preconditioning signaling and non-signaling periods, the preconditioning cardiac biologic therapies each having a preconditioning therapy duration in a range of approximately 2 minutes to 1 hour, the preconditioning signaling period each having a preconditioning signal duration in a range of approximately 1 minute to 30 minutes during which the at least one gene regulatory signal is delivered, the preconditioning non-signaling period having a preconditioning non-signal duration in a range of approximately 1 minute to 30 minutes during which the at least one gene regulatory signal is not delivered.

8. The method of claim 1, further comprising:

detecting an arrhythmia; and

suspending the one or more cardiac protection biologic therapies when the arrhythmia is detected.

9. The method of claim 1, wherein delivering the at least one gene regulatory signal comprises generating an electric field having frequency and strength parameters selected for regulating the regulatable transcriptional control element.

10. The method of claim 1, wherein delivering the at least one gene regulatory signal comprises generating an electromagnetic field having frequency and strength parameters selected for regulating the regulatable transcriptional control element.

11. The method of claim 1, wherein delivering the at least one gene regulatory signal comprises emitting a light having wavelength and intensity parameters selected for regulating the regulatable transcriptional control element.

12. The method of claim 1, wherein delivering the at least one gene regulatory signal comprises emitting an acoustic signal having frequency and intensity parameters selected for regulating the regulatable transcriptional control element.

13. The method of claim 1, wherein delivering the at least one gene regulatory signal comprises emitting one or more chemical agents regulating the regulatable transcriptional control element.

14. The method of claim 1, wherein delivering the at least one gene regulatory signal comprises emitting a thermal energy for regulating the regulatable transcriptional control element.

15. The method of claim 1, wherein initiating the one or more cardiac protection biologic therapies in response to the detection of the ischemic event comprises initiating a postconditioning cardiac biologic therapy of the one or more cardiac protection biologic therapies in response to expiration of a post-ischemia time interval that starts at the end of the ischemic event and ends after a predicted reperfusion period following the ischemic event has started.

16. A method for cardiac protection, the method comprising:

receiving a command;

sensing one or more parameters indicative of an ischemic event using an implantable medical device;

detecting the ischemic event from the one or more parameters, including detecting an end of the ischemic event, using the implantable medical device;

initiating one or more cardiac protection biologic therapies in response to one or more of the reception of the command and the detection of the ischemic event, the one or more cardiac protection biologic therapies each including at least one signaling and non-signaling period, the at least one signaling period having a signaling duration during which at least one gene regulatory signal is delivered, the at least one non-signaling period having a non-signaling duration during which the at least one gene regulatory signal is not delivered, the at least one gene regulatory signal is capable of directly or indirectly regulating a regulatable transcriptional control element without inducing cardiac depolarization, the regulatable transcriptional control element is operably linked to an open reading frame forming an expression cassette, wherein the expression cassette is present in the mammal, and wherein expression of the open reading frame in an effective amount inhibits damage to cardiac tissue resulting from ischemia; and

delivering the at least one gene regulatory signal from the implantable medical device during at least one of the signaling periods,

wherein initiating the one or more cardiac protection biologic therapies comprises initiating at least one postconditioning cardiac biologic therapy using the implantable medical device in response to one or more of the reception of the command and when a post-ischemia time interval expires, the post-ischemia time interval starting at the detected end of the ischemic event and ending after a predicted reperfusion period following the ischemic event has started.

17. The method of claim 16, wherein receiving the command comprises receiving the command using a user input device of an external system communicatively coupled to the implantable medical device.

18. The method of claim 17, wherein delivering the at least one gene regulatory signal comprises generating an electric or electromagnetic field having frequency and strength parameters selected for regulating the regulatable transcriptional control element.

19. The method of claim 16, wherein the post-ischemia time interval is up to approximately 10 minutes.

20. The method of claim 16, comprising timing the signaling and non-signaling durations each being a duration between approximately 5 seconds and 30 minutes.