Method and apparatus for device controlled gene expression for cardiac protection

• US 7,774,057 B2
• Filed: 09/06/2005
• Issued: 08/10/2010
• 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: Baynham, Tamara Colette, Spinelli, Julio C., Pastore, Joseph M., Kramer, Andrew P., Salo, Rodney W., Ross, Jeffrey
• Primary Examiner(s): Layno; Carl H
• Assistant Examiner(s): Behringer; Luther G
• Application Number:
  US11/220,397
• Publication Number:
  US 20070054871A1
• Time in Patent Office: 1,799 Days
• Field of Search: 424/93.21, 435/6, 514/12, 514/44, 607/2, 607/9, 607/3, 623/1.13, 623/1.15
• US Class Current: 607/3
• 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 gene regulatory system, comprising:

a sensing circuit to sense one or more parameters indicative of an ischemic event;

an ischemia detector, coupled to the sensing circuit, to detect an end of the ischemic event from the one or more parameters;

a gene regulatory signal delivery device adapted to emit at least one gene regulatory signal that directly or indirectly regulates a regulatable transcriptional control element without inducing cardiac depolarization; and

a controller coupled to the ischemia detector and the gene regulatory signal delivery device, the controller being a microprocessor-based control circuit including;

a gene regulatory initiator adapted to initiate one or more cardiac protection biologic therapies in response to the detection of the end of the ischemic event, the one or more cardiac protection biologic therapies each including alternating signaling periods and non-signaling periods, the signaling periods each having a signaling duration during which the at least one gene regulatory signal is emitted, the non-signaling periods each having a non-signaling duration during which the at least one gene regulatory signal is not emitted, the gene regulatory initiator including a postconditioning initiator adapted to initiate 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; and

a gene regulatory timer adapted to time the one or more cardiac protection biologic therapies.

2. The system of claim 1, wherein the gene regulatory signal delivery device comprises an electric field generator adapted to generate an electric field having frequency and strength parameters selected for regulating the regulatable transcriptional control element.

3. The system of claim 1, wherein the gene regulatory signal delivery device comprises an electromagnetic field generator adapted to generate an electromagnetic field having frequency and strength parameters selected for regulating the regulatable transcriptional control element.

4. The system of claim 1, wherein the postconditioning initiator is adapted to initiate the postconditioning cardiac biologic therapy in response to expiration of a post-ischemia time interval of approximately 30 seconds.

5. The system of claim 1, wherein the gene regulatory initiator comprises a preconditioning initiator adapted to initiate a plurality of preconditioning cardiac biologic therapies in response to the detection of the ischemic event, the preconditioning cardiac biologic therapies each being one of the one or more cardiac protection biologic therapies.

6. The system of claim 5, wherein the preconditioning initiator is adapted to initiate the preconditioning cardiac biologic therapies on a periodic basis using a predetermined period.

7. The system of claim 5, wherein the preconditioning initiator is adapted to initiate the preconditioning cardiac biologic therapies in response to one or more preconditioning commands.

8. The system of claim 1, wherein the controller is adapted to detect an arrhythmia and to suspend the one or more cardiac protection biologic therapies in response to the detection of the arrhythmia.

9. The system of claim 1, further comprising an implantable medical device including at least the ischemia detector and the controller, the ischemia detector adapted to produce an ischemia alert signal indicative of the detection of the ischemic event, the implantable medical device adapted to produce an audible alarm signal in response to the ischemia alert signal.

10. The system of claim 1, further comprising:

an implantable medical device including at least the ischemia detector and the controller, the ischemia detector adapted to produce an ischemia alert signal indicative of the detection of the ischemic event; and

an external system communicatively coupled to the implantable medical device, the external system comprises;

an external controller adapted to receive the ischemia alert signal; and

a presentation device configured to present at least one of an alarm signal and a warning message in response to the ischemia alert signal.

11. The system of claim 10, wherein the external system comprises a user input device to receive one or more gene regulatory commands, and the gene regulatory initiator is adapted to initiate the one or more cardiac protection biologic therapies in response to the detection of the ischemic event and the one or more gene regulatory commands.

12. The system of claim 1, wherein the gene regulatory timer is adapted to time signaling periods each having a signaling duration between approximately 5 seconds and 30 minutes.

13. A system, comprising:

an implantable medical device system including;

an implant telemetry module to receive an external command;

a gene regulatory signal delivery device adapted to emit at least one gene regulatory signal which directly or indirectly regulates a regulatable transcriptional control element without inducing cardiac depolarization;

a sensing circuit to sense a physiological parameter indicative of an ischemic event; and

an ischemia detector, coupled to the sensor, to detect an end of the ischemic event from the sensed physiological parameter; and

an implant controller coupled to the ischemia detector and the implant telemetry module, the implant controller including a gene regulatory control module adapted to initiate and control the emission of the at least one gene regulatory signal based on one or more of the sensed physiological parameter and the external command, the gene regulatory control module including;

a gene regulatory initiator adapted to initiate one or more cardiac protection biologic therapies in response to at least one of expiration of a post-ischemia time interval and the reception of the external command, the one or more cardiac protection biologic therapies each including at least one signaling period and at least one non-signaling period, wherein each signaling period has a signaling duration during which the at least one gene regulatory signal is emitted and each non-signaling period has a non-signaling duration during which the at least one gene regulatory signal is not emitted, the post-ischemia time interval starting at the end of the ischemic event and ending after a predicted reperfusion period following the ischemic event has started; and

a gene regulatory timer adapted to time the one or more cardiac protection biologic therapies including the signaling duration being a duration between approximately 5 seconds and 30 minutes and the non-signaling duration being a duration between approximately 5 seconds and 30 minutes; and

an external system including an external telemetry module to transmit the external command to the implant telemetry module.

14. The system of claim 13, wherein the gene regulatory initiator comprises a postconditioning initiator adapted to initiate at least one postconditioning cardiac biologic therapy in response to the expiration of the post-ischemia time interval, the postconditioning cardiac biologic therapy being one of the one or more cardiac protection biologic therapies.

15. The system of claim 14, wherein the gene regulatory initiator comprises a preconditioning initiator adapted to initiate preconditioning cardiac biologic therapies on a periodic basis in response to the detection of the ischemic event, the preconditioning cardiac biologic therapies each being one of the one or more cardiac protection biologic therapies.