Protein activity modification

• US 20100016923A1
• Filed: 05/04/2006
• Published: 01/21/2010
• Est. Priority Date: 03/10/2004
• Status: Active Grant

• Current Assignee: Impulse Dynamics NV
• Original Assignee: Impulse Dynamics NV
• Inventors: Rousso, Benny, Ben-Haim, Shlomo, Sabbah, Hani N., Mika, Yuval
• Granted Patent: US 8,548,583 B2
• Time in Patent Office: Days
• US Class Current: 607/59
• CPC Class Codes: A61N 1/205 for promoting a biological process
• CPC Class Codes: A61N 1/32 alternating or intermittent currents applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02
• 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 1/3628 using sub-threshold or non-excitatory signals
• CPC Class Codes: A61N 1/3629 in combination with non-electric therapy
• CPC Class Codes: A61N 2/004 specially adapted for a specific therapy
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

A method of modifying tissue behavior, comprising:

• • determining a desired modification of tissue behavior for at least one of treatment of a disease, short or long term modification of tissue behavior, assessing tissue state and assessing tissue response to stimulation;
  • selecting an electric field having an expected effect of modifying protein activity of at least one protein as an immediate response of a tissue to the field, said expected effect correlated with said desired modification; and
  • applying said field to said tissue.

Claims

1. A method of modifying tissue behavior, comprising:

determining a desired modification of tissue behavior for at least one of treatment of a disease, short or long term modification of tissue behavior, assessing tissue state and assessing tissue response to stimulation;

selecting an electric field having an expected effect of modifying protein activity of at least one protein as an immediate response of a tissue to the field, said expected effect correlated with said desired modification; and

applying said field to said tissue.

3. A method according to claim 1, wherein said tissue comprises cardiac tissue.

8. A method according to claim 1, wherein said at least one protein comprises phospholamban.

17. A method according to claim 1, wherein modifying comprises phosphorylation.

18. A method according to claim 1, wherein modifying comprises dephosphorylation.

34. A method according to claim 1, wherein said modification is a long term modification which comprises changes in protein expression levels.

39. A method according to claim 1, wherein said treatment of a disease comprises reversing a heart failure state in said tissue.

2. (canceled)

4-7. -7. (canceled)

9-16. -16. (canceled)

19-33. -33. (canceled)

35-38. -38. (canceled)

40-74. -74. (canceled)

75. Apparatus for treating tissue, comprising:

at least one electrode adapted to apply an electric field to in-vivo tissue;

a controller including a memory having stored therein at least one electric field sequence which modifies protein activity in said tissue, said controller being configured to determine that a modification of said protein activity is desired and apply said sequence in response said determination.

76. Apparatus according to claim 75, wherein said controller memory has stored therein a plurality of sequences or sequence parameters and wherein said controller is configured to select between the sequences or parameters.

77. Apparatus according to claim 75, comprising an input and wherein said controller makes said determination according to a signal received on said input.

78. A method of manufacturing a therapeutic device comprising:

selecting a pulse sequence according to its effect on protein activity modification; and

programming a controller of said therapeutic device to apply said sequence.

79-81. -81. (canceled)

82. A method of tissue treatment, comprising:

providing a plurality of tissue plugs;

applying an electric field to said plugs to modify biochemical behavior thereof; and

implanting said plugs.

83-85. -85. (canceled)

86. A method of therapy, comprising:

selectively applying a therapy material to a tissue; and

selectively modifying protein activity in said tissue utilizing a second therapy.

87-91. -91. (canceled)

92. A method of modifying tissue behavior, comprising:

determining a desired modification of tissue behavior for at least one of treatment of a disease, short or long term modification of tissue behavior, assessing tissue state and assessing tissue response to stimulation;

selecting a tissue modifying activity having an expected effect of modifying protein activation levels of at least one protein as an immediate response of a tissue to the activity, said expected effect correlated with said desired modification; and

applying said activity to said tissue.

93-95. -95. (canceled)

96. A biochemical assaying kit, comprising:

an indicator of protein phosphorylation; and

instructions for using said phosphorylation as an indicator of tissue state.

97-101. -101. (canceled)

102. Apparatus for treating cardiac dysfunction, comprising:

at least one electrode adapted to apply an electric field to tissue of a patient; and

a controller configured to apply an electrical sequence in spurts of applications with delays between the spurts, said field being configured to have an affirmative modifying effect which modifies a behavior of said tissue in a positive manner, such that a lasting effect from a spurt continues for a significant time after the spurt.

103-119. -119. (canceled)

120. A method of treating a patient with an electrical therapy, comprising:

applying an electrical field to an organ of the patient;

stopping said application for a length of time which is a function of an expected washout time of an effect of said field.

121. A method according to claim 120, wherein said organ is a heart.

125. A method according to claim 120, wherein said effect is a long-term effect.

129. A method according to claim 120, wherein said effect is selected to be a change in one or more of ejection fraction, cardiac muscle dimension, cardiac chamber dimension, quality of life as measured by a questionnaire, peak oxygen consumption, anaerobic tolerance, 6 meter walk distance, fluid retention, sleep apnea severity, and exercise tolerance.

122-124. -124. (canceled)

126-128. -128. (canceled)

130-131. -131. (canceled)

132. A method of therapy location placement for therapy of tissue, comprising:

applying a test therapy to the tissue; and

deciding on suitability of the placement based on an effect of protein activity levels of said test therapy.

133-134. -134. (canceled)

135. A method of therapy location placement for therapy of tissue, comprising:

providing an organ to be treated; and

selecting at least one location of treatment, according to a desired propagation of biochemical effect of said treatment in said organ.

136-138. -138. (canceled)

139. A method of therapy location placement for therapy of tissue, comprising:

applying a test therapy to the tissue; and

deciding on suitability of the placement based on an effect of protein activity levels of said test therapy, even if an improvement in organ function is not detected.

140-141. -141. (canceled)

142. A method of therapy, comprising:

applying a therapy at a first location;

determining if the therapy is having a first effect by measuring a short term response at said first location; and

determining if the therapy is having a second effect by measuring a long-term response at a second, untreated, location.

143-144. -144. (canceled)

145. A method of treating cardiac tissue, comprising:

selecting a tissue with reduced oxygen transport thereto; and

applying an electric field to said tissue, which field does not reduce activity thereof.

146-163. -163. (canceled)

164. A method of treating cardiac dysfunction, comprising:

determining a desired effect on protein activity; and

applying a field to cardiac tissue to cause such desired change.

165-167. -167. (canceled)

168. A method of treating cardiac dysfunction, comprising applying an electric field to a heart which is sufficient to have a significant normalization effect on protein phosphorylation levels without significant effect on contractility.

169. Apparatus for delivering an electric field to cardiac tissue, being programmed to use a minimum amount of power sufficient to affect positively the phosphorylation of HF-related proteins.

170. A method of treating tissue, comprising:

determining a desired effect on levels of at least one of phospholamban and phosphorylation thereof; and

applying a field to tissue to cause such desired change.

171. A method of treating cardiac tissue, comprising:

selecting a signal according to its not being expected to increase mean oxygen consumption; and

applying an electric field with said signal to cardiac tissue, which field does not reduce activity thereof.

172. A method of manufacturing a cardiac device, comprising:

selecting a signal which is expected not to increase mean oxygen consumption while not reducing tissue activity; and

programming a cardiac device with said signal.

173. A cardiac controller, comprising:

a signal application circuit adapted to apply a first signal which increases mean oxygen consumption and second signal which does not increase said oxygen consumption; and

a control circuit adapted to control said signal application circuit to selectively apply one of said two signals, based on oxygen availability.