US 2021/0196697 A1 · COMBINATION THERAPIES FOR TREATING BIPOLAR DISORDER AND ADHD, 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 attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BD). The invention relates to combination therapies for the treatment of BD and for ADHD, and methods for treating BD and ADHD using such therapies. The present invention also relates to methods of determining an optimal combination drug treatment therapy for BD and for ADHD, methods of optimizing a combination drug treatment therapy for BD and for ADHD, methods of optimizing dosage of a drug in a combination drug treatment therapy for BD and for ADHD, as well as methods for monitoring the efficacy of a combination therapy for the treatment of BD and for ADHD. The present invention involves analyzing the membrane potential of cells isolated from a BD patient treated with the combination therapy and from an ADHD patient treated with the combination therapy, and calculating a membrane potential ratio therefrom.

Claims36

Dependent claims

A method of determining an optimal combination drug treatment therapy for a patient with attention deficit hyperactivity disorder (ADHD), comprising:

obtaining a ratio of a mean membrane potential that is a mean membrane potential of a first population of cells from the ADHD 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 ADHD 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 ADHD 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) an ADHD control ratio of a mean membrane potential of first population of bipolar control human cells known to have ADHD 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 ADHD 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 decreased towards the control ratio in comparison to the ADHD control ratio of (b), and/or is significantly lower than the ADHD control ratio in (b).

2 more elements

A method of optimizing a combination drug treatment therapy for a patient with attention deficit hyperactivity disorder (ADHD), comprising the steps of:

obtaining at least one sample from a ADHD patient in a drug therapy treatment for ADHD;
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 ADHD 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) an ADHD control ratio of a mean membrane potential of a first population of ADHD control human cells known to have ADHD 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 ADHD 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 ADHD 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 decreased towards the control ratio in comparison to the ADHD control ratio of (b), and/or is significantly lower than the ADHD control ratio of (b);
and
optionally, modifying at least one drug in the drug therapy treatment for ADHD when the least one drug treatment therapy for ADHD 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 attention deficit hyperactivity disorder (ADHD), said method comprising:

obtaining at least one sample from a ADHD 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 ADHD 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 ADHD 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 ADHD 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) an ADHD control ratio of a mean membrane potential of a first population of cells from a ADHD control human known to have said ADHD 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 ADHD 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 ADHD 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 decreased towards the control ratio in comparison to the ADHD control ratio of (b), and/or is significantly lower than the ADHD 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 ADHD 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 attention deficit hyperactivity disorder (ADHD), said method comprising:

obtaining at least one sample from a ADHD patient treated with a combination drug treatment therapy for treating ADHD;
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 ADHD 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 ADHD 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 ADHD 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) an ADHD control ratio of a mean membrane potential of a first population of cells from a ADHD control human known to have said ADHD 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 ADHD 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 decreased towards the control ratio in comparison to the ADHD control ratio of (b), and/or is significantly lower than the ADHD 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 adhd, and methods for using the same

Life of this patent

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

Life of this patent

Abstract

Claims36