US 2019/0302102 A1 · COMBINATION THERAPIES FOR TREATING BIPOLAR DISORDER, AND METHODS FOR USING THE SAME

Abstract

The present invention relates to pharmaceutical combinations and compositions, and methods of using the same for treatment of Bipolar Disorder (BD). More specifically, the invention relates to combination therapies for the treatment of BD, and methods for treating BD using such therapies. The present invention also relates to methods of determining an optimal combination drug treatment therapy for BD, methods of optimizing a combination drug treatment therapy for BD, methods of optimizing dosage of a drug in a combination drug treatment therapy for BD, as well as methods for monitoring the efficacy of a combination therapy for the treatment of BD. The present invention involves analyzing the membrane potential of cells isolated from a BD patient treated with the combination therapy, and calculating a membrane potential ratio therefrom.

Claims63

Dependent claims

A method of determining an optimal combination drug treatment therapy for a patient with bipolar disorder (BD), comprising:

obtaining a ratio of a mean membrane potential that is a mean membrane potential of a first population of cells from the BD patient incubated in vitro in the presence of an agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of cells from the BD patient incubated in vitro in the absence of the test agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+;
comparing the ratio of the mean membrane potential to (a) and/or (b):
(a) a control ratio of a mean membrane potential of first population of control human cells known to not have BD incubated in vitro in the presence of the agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of the control human cells incubated in vitro in the absence of the agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+,
(b) a bipolar control ratio of a mean membrane potential of first population of bipolar control human cells known to have BD incubated in vitro in the presence of the agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of the bipolar control human cells incubated in vitro in the absence of the agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+:
identifying the optimal combination drug treatment therapy when the ratio of the mean membrane potential obtained is not significantly different from the control ratio in (a), is increased towards the control ratio in comparison to the bipolar control ratio of (b), and/or is significantly higher than the BD control ratio in (b).

2 more elements

A method of optimizing a combination drug treatment therapy for a patient with bipolar disorder (BD), comprising the steps of:

obtaining at least one sample from a BD patient in a drug therapy treatment for BD;
performing on each sample, a mean membrane potential test comprising:
obtaining a ratio of a mean membrane potential that is a mean membrane potential of a first population of cells from the sample incubated in vitro in the presence of an agent that alters diacylglycerol signaling and in the absence of K+ to a mean membrane potential of a second population of the sample incubated in vitro in the absence of the test agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+;
comparing the ratio of the mean membrane potential to (a) and/or (b):
(a) a control ratio of a mean membrane potential of a first population of control human cells known to not have BD incubated in vitro in the presence of the agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of the control human cells incubated in vitro in the absence of the agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+,
(b) a bipolar control ratio of a mean membrane potential of a first population of bipolar control human cells known to have BD incubated in vitro in the presence of the agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of the bipolar control human cells incubated in vitro in the absence of the agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+:
determining an optimal drug therapy treatment for the BD patient based on the mean membrane potential test when the ratio of the mean membrane potential obtained is not significantly different from the control ratio of (a), is increased towards the control ratio in comparison to the bipolar control ratio of (b), and/or is significantly higher than the BD control ratio of (b);
and
optionally, modifying at least one drug in the drug therapy treatment for BD when the least one drug treatment therapy for BD is determined to not be the optimal drug therapy treatment based on the mean membrane potential test.

6 more elements

A method for determining an optimum dosage of a drug in a combination drug treatment therapy for the treatment of bipolar disorder (BD), said method comprising:

obtaining at least one sample from a BD patient treated with a dosage of a drug in a combination therapy;
performing on each sample, a mean membrane potential test comprising:
obtaining a ratio of a mean membrane potential that is a mean membrane potential of a first population of cells from the BD patient incubated in vitro in the presence of an agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of cells from the BD patient incubated in vitro in the absence of the test agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+;
comparing the ratio of the mean membrane potential to (a) and/or (b):
(a) a control ratio of a mean membrane potential of a first population of cells from a control human known to not have said BD incubated in vitro in the presence of the agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of cells from the control human incubated in vitro in the absence of the agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+,
(b) a bipolar control ratio of a mean membrane potential of a first population of cells from a bipolar control human known to have said BD incubated in vitro in the presence of the agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of cells from the bipolar control human incubated in vitro in the absence of the agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+;
determining the dosage of the drug in the combination drug treatment therapy is an optimal dosage for treating BD in the combination therapy based on the mean membrane potential test when the ratio of the mean membrane potential obtained is not significantly different from the control ratio of (a), is increased towards the control ratio in comparison to the bipolar control ratio of (b), and/or is significantly higher than the BD control ratio of (b);
and
optionally, modifying the dosage of the drug in the combination drug treatment therapy when the dosage of the drug in the combination therapy is determined to be not the optimal dosage for treating BD based on the mean membrane potential test.

6 more elements

A method for monitoring the efficacy of a combination drug treatment therapy for the treatment of bipolar disorder (BD), said method comprising:

obtaining at least one sample from a BD patient treated with a combination drug treatment therapy for treating BD;
performing on each sample, a mean membrane potential test comprising:
obtaining a ratio of a mean membrane potential that is a mean membrane potential of a first population of cells from the BD patient incubated in vitro in the presence of an agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of cells from the BD patient incubated in vitro in the absence of the test agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+;
comparing the ratio of the mean membrane potential to (a) and/or (b):
(a) a control ratio of a mean membrane potential of a first population of cells from a control human known to not have said BD incubated in vitro in the presence of the agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of cells from the control human incubated in vitro in the absence of the agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+,
(b) a bipolar control ratio of a mean membrane potential of a first population of cells from a bipolar control human known to have said BD incubated in vitro in the presence of the agent that alters diacylglycerol signaling and in the absence of K+, to a mean membrane potential of a second population of cells from the bipolar control human incubated in vitro in the absence of the agent that alters diacylglycerol signaling and in the presence of K+ or absence of K+;
determining the combination drug treatment therapy is efficacious based on the mean membrane potential test when the ratio of the mean membrane potential obtained is not significantly different from the control ratio in (a), is increased towards the control ratio in comparison to the bipolar control ratio of (b), and/or is significantly higher than the BD control ratio in (b);
and
optionally, adjusting a dosage of one or more agents in the combination drug treatment therapy when the combination therapy is determined to be not efficacious based on the mean membrane potential test.

6 more elements

Dependencies are inferred from the claim text.

Combination therapies for treating bipolar disorder, and methods for using the same

Life of this patent

Combination therapies for treating bipolar disorder, and methods for using the same

Life of this patent

Abstract

Claims63