Systems and devices for photoablation

• US 20090054883A1
• Filed: 08/22/2007
• Published: 02/26/2009
• Est. Priority Date: 08/22/2007
• Status: Active Grant

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Pastore, Joseph M., Sweeney, Robert J., Stolen, Craig
• Granted Patent: US 8,480,662 B2
• Time in Patent Office: Days
• US Class Current: 606/14
• CPC Class Codes: A61N 2005/063 comprising light transmitting means, e.g. optical fibres
• CPC Class Codes: A61N 2005/0651 Diodes
• 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

Abstract

The invention provides a catheter for optical ablation of tissue in a living body, the catheter including: a distal end; a proximal end; an elongate catheter body coupled between the distal end and the proximal end; a light emission device at the distal end and configured to emit an ablation light having characteristics selected to regulate an optically regulatable transcription control element operably linked to a nucleic acid sequence for a gene product, the expression of which gene product in cells directly or indirectly kills cells; and a projection control mechanism coupled to the light emission device and configured to control an effectively illuminated area where the optically regulatable transcription control element is effectively regulatable by the ablation light projected from the light emission device. Also provided is a system which includes the catheter, and methods to prevent, inhibit or treat AF which employ an expression cassette and/or one or more selected wavelengths of light.

Claims

1. A catheter for optical ablation of tissue in a living body, the catheter comprising:

a distal end;

a proximal end;

an elongate catheter body coupled between the distal end and the proximal end;

a light emission device at the distal end and configured to emit an ablation light having characteristics selected to regulate an optically regulatable transcription control element operably linked to a nucleic acid sequence for a gene product, the expression of which gene product in cells directly or indirectly kills cells; and

a projection control mechanism coupled to the light emission device and configured to control an effectively illuminated area where the optically regulatable transcription control element is effectively regulatable by the ablation light projected from the light emission device.

2. The catheter of claim 1 wherein the light emission device is configured to emit a light having a wavelength from 300 to 1500 nanometers and selected to regulate the optically regulatable transcription control element.

3. The catheter of claim 1 wherein the light emission device comprises one or more light emitting diodes (LEDs) configured to emit the ablation light, and comprising electrical conductors extending within the elongate catheter body, and an electrical connector at the proximal end and connected to the one or more LEDs via the electrical conductors.

4. The catheter of claim 1 wherein the light emission device comprises a distal terminal of an fiber optic cable configured to transmit the ablation light received at the proximal end, and comprising a fiber optic cable and an optical connector at the proximal end and connected to the fiber optic cable.

5. The catheter of claim 1 wherein the light emission device comprises an elongate light emission device, and the projection control mechanism comprises a non-transparent shield over the elongate light emission device and a slit on the shield, wherein the ablation light is projected from the light projector through the slit.

6. The catheter of claim 1 wherein the light emission device comprises a plurality of light emission devices, and the projection control mechanism comprises a mesh balloon coupled to the distal end, and the light emission devices are distributed over the mesh.

7. The catheter of claim 1 wherein the projection control mechanism comprises an adjustable projection control mechanism configured to adjustably control the effectively illuminated area, the adjustable projection control mechanism including:

a distal projection control device coupled to the light emission device;

a proximal projection control device at the proximal end and configured to allow for control of the effectively illuminated area from the proximal end; and

a projection control link extending within the elongate body and coupled between the distal projection control device and the proximal projection control device.

8. The catheter of claim 7 wherein the distal projection control device comprises a diaphragm coupled to the light emission device and configured to control the projection of the ablation light, the diaphragm including an adjustable aperture configured to determine the amount of light projected from the light emission device.

9. The catheter of claim 7 wherein the light emission device comprises an elongate light emission device, the distal projection control device comprises a retractable non-transparent sleeve surrounding at least a portion of the elongate light emission device, the retractable non-transparent sleeve configured to slide over the elongate light emission device to determine the amount of the light projected from the elongate light emission device.

10. The catheter of claim 7 wherein the distal projection control device comprise a transparent bubble coupled to the distal end of the optical ablation catheter and a light positioning device connected to the light emission device, the light positioning device configured to allow the light emission device to be adjustably positioned in a transparent bubble.

11. The catheter of claim 10 wherein the bubble is adapted for delivery of light to the pulmonary vein ostia.

12. The catheter of claim 7 wherein the distal projection control device comprises a light positioning device configured to be slid along a portion of the optical ablation catheter, and the light emission device is attached onto the light positioning device.

13. The catheter of claim 7 further comprising a sensing device configured to allow for sensing of one or more physiological signals, the sensing device including one or more electrodes at the distal end.

14. The catheter of claim 1 further comprising a location device including a magnetic field location sensor at the distal end and configured to sense a location signal indicative of a location of the distal end.

15. The catheter of claim 1 further comprising a radio-frequency (RF) ablation device including a thermal energy emitter at the distal end and configured to generate a thermal energy suitable for ablating the tissue using an RF signal.

16. The catheter of claim 1 further comprising a cryoablation device.

17. A system comprising:

a catheter for optical ablation of tissue in a living body, the catheter comprising;

a distal end;

a proximal end;

an elongate catheter body coupled between the distal end and the proximal end;

a light emission device at the distal end and configured to emit an ablation light having characteristics selected to regulate an optically regulatable transcription control element operably linked to a nucleic acid sequence for a gene product; and

a projection control mechanism coupled to the light emission device and configured to control an effectively illuminated area where the optically regulatable transcription control element is effectively regulatable by the ablation light projected from the light emission device; and

two expression cassettes, wherein a first expression cassette comprises the optically regulatable transcription control element operably linked to a nucleic acid sequence that encodes a suicide enzyme and wherein a second expression cassette comprises the optically regulatable transcription control element operably linked to a nucleic acid sequence that encodes an inhibitor of conduction.

18. A method to prevent, inhibit or treat AF, comprising:

administering to a mammal having or at risk of AF, a composition comprising an expression cassette comprising a device-regulatable transcription control element operably linked to a nucleic acid sequence for a gene product, the expression of which gene product in cells directly or indirectly kills the cells, and wherein a regulatory signal from the device increases expression from the regulatable transcription control element; and

delivering to a selected cardiac region of the mammal the regulatory signal in an effective amount.

19. The method of claim 18 wherein the regulatable transcription control element is regulatable by one or more selected wavelengths of light.

20. The method of claim 18 wherein a catheter delivers the regulatory signal.

21. The method of claim 18 wherein the gene product encodes a suicide enzyme and wherein the composition further comprises a second expression cassette comprising a device-regulatable transcription control element operably linked to a nucleic acid sequence encoding an inhibitor of conduction.

22. The method of claim 21 further comprising detecting whether conduction induced by electrophysiology testing in cells having the second expression cassette is inhibited.

23. The method of claim 22 further comprising administering a prodrug which is converted to a toxin by the suicide enzyme.

24. A method to prevent, inhibit or treat atrial fibrillation (AF), comprising:

administering to a mammal having or at risk of AF a caged photolabile toxin; and

delivering an effective amount of one or more selected wavelengths of light to a selected cardiac region of the mammal.

25. The method of claim 24 wherein the light is delivered by a catheter.

26. A method to prevent, inhibit or treat AF, comprising:

administering to a mammal having or at risk of AF, a first moiety comprising a quencher linked to a first oligonucleotide with a nucleotide sequence that forms a hairpin linked to a chromophore or fluorophore linked to a photosensitive linker linked to a cytotoxic agent, and a second moiety comprising a second oligonucleotide capable of forming a double stranded base paired molecule with the nucleotide sequence in the first oligonucleotide; and

delivering to cells one or more selected wavelengths of light, so as to cleave the photosensitive linker, yielding an effective amount of cytotoxic agent.

27. The method of claim 26 wherein the first moiety comprises the fluorophore.

28. The method of claim 27 further comprising detecting fluorescence in the cells of the mammal;

and

delivering to cells which fluoresce the one or more selected wavelengths of light.

29. A method to prevent, inhibit or treat AF, comprising:

administering to a mammal having or at risk of AF, a first moiety comprising a quencher linked to a first oligonucleotide with a nucleotide sequence that forms a hairpin linked to a photosensitive linker linked to a cytotoxic agent, and a second moiety comprising a second oligonucleotide capable of forming a double stranded base paired molecule with the nucleotide sequence in the first oligonucleotide, wherein in the absence of the second moiety, the quencher blocks light capable of cleaving the linker; and

delivering to cells one or more selected wavelengths of light, so as to cleave the photosensitive linker, yielding an effective amount of cytotoxic agent.

30. The method of claim 29 wherein the second moiety is administered after the first moiety.