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US-20260124180-A1 - METHOD OF TREATING AFFECTIVE DISORDERS AND PERSONALITY DISORDERS

US20260124180A1US 20260124180 A1US20260124180 A1US 20260124180A1US-20260124180-A1

Abstract

As described below, the present invention features compositions and methods for treating brain and/or behavioral health disorders and their associated symptoms.

Inventors

  • Alon Seifan

Assignees

  • HB BIOTECH, INC.

Dates

Publication Date
20260507
Application Date
20260105

Claims (17)

  1. 1 . A method for improving cognitive function and/or life satisfaction in a subject, the method comprising administering to the subject a combination therapy comprising a first agent selected from the group consisting of anipamil, devapamil, falipamil, gallopamil, tiapamil, and verapamil and a second agent that is telmisartan or candesartan.
  2. 2 . The method of claim 1 , wherein the second agent is telmisartan.
  3. 3 . The method of claim 1 , wherein the effective amount of the first agent is from about 120 mg to about 720 mg and the effective amount of the second agent is from about 45 mg to about 180 mg.
  4. 4 . The method of claim 1 , wherein the combination therapy comprises 120-360 mg of verapamil and 40 to 180 of telmisartan.
  5. 5 . The therapeutic combination of claim 1 , wherein the therapeutic combination further comprises magnesium oxide.
  6. 6 . The method of claim 1 , wherein the therapeutic combination is administered once or twice daily.
  7. 7 . The method of claim 1 , wherein the amount of the first agent is from about 1 to about 4 times the amount of the second agent.
  8. 8 . A method of treating a neurodevelopmental disorder in a subject, the method comprising administering to the subject a combination therapy comprising a first agent selected from the group consisting of anipamil, devapamil, falipamil, gallopamil, tiapamil, and verapamil; and a second agent that is telmisartan or candesartan, wherein the neurodevelopmental disorder is selected from the group consisting of autism spectrum disorder, attention deficit hyperactive disorder (ADHD) and learning disorder.
  9. 9 . The method of claim 8 , wherein the first agent is verapamil and the second agent is telmisartan.
  10. 10 . The method of claim 8 , wherein the effective amount of the first agent is from about 120 mg to about 720 mg and the effective amount of the second agent is from about 45 mg to about 180 mg.
  11. 11 . The method of claim 8 , wherein the combination therapy comprises 120-360 mg of verapamil and 40 to 180 of telmisartan.
  12. 12 . The method of claim 8 , wherein the therapeutic combination is administered once or twice daily.
  13. 13 . A pharmaceutical composition comprising effective amounts of a first and second agent and a pharmaceutically acceptable excipient, wherein the first agent is selected from the group consisting of anipamil, devapamil, falipamil, gallopamil, tiapamil, and verapamil and the second agent is selected from one or more of telmisartan and candesartan.
  14. 14 . A kit comprising a therapeutic combination comprising a therapeutic combination comprising a first and second agent, wherein the first agent is selected from the group consisting of anipamil, devapamil, falipamil, gallopamil, tiapamil, and verapamil and the second agent is selected from one or more of telmisartan and candesartan, and instructions for the use of the combination for the treatment of a brain and/or behavioral health disorder or a symptom thereof.
  15. 15 . A method of treating addition and/or substance abuse in a subject, the method comprising administering to the subject a combination therapy comprising a first agent selected from the group consisting of anipamil, devapamil, falipamil, gallopamil, tiapamil, and verapamil; and a second agent that is telmisartan or candesartan.
  16. 16 . A method of treating a migraine disorder and/or somatoform disorder in a subject, the method comprising administering to the subject a combination therapy comprising a first agent selected from the group consisting of anipamil, devapamil, falipamil, gallopamil, tiapamil, and verapamil; and a second agent that is telmisartan or candesartan.
  17. 17 . A method of treating a psychotic disorder in a subject, the method comprising administering to the subject a combination therapy comprising a first agent selected from the group consisting of anipamil, devapamil, falipamil, gallopamil, tiapamil, and verapamil; and a second agent that is telmisartan or candesartan, thereby effecting an improvement in cognitive function and/or life satisfaction in the subject.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional of U.S. application Ser. No. 17/996,413, filed Oct. 17, 2022, which is a U.S. National Stage Application under 35 U.S.C § 371 of PCT International Application No. PCT/US2021/027641, filed Apr. 16, 2021, which claims the benefit of and priority to U.S. Provisional Application Nos. 63/011,932, filed Apr. 17, 2020, and 63/111,156, filed Nov. 9, 2020, the entire contents of each of which are incorporated by reference herein. BACKGROUND Brain and behavioral health disorders are the number one cause of disability worldwide. Brain and behavioral health disorders include all of the major disorders that belong to neurology, psychiatry and psychology subspecialties. Anxiety, apathy, cognitive difficulty, depression, fatigue, headache, insomnia, irritability, pain (e.g., body pain), and psychosis are ten cardinal symptoms caused by brain and behavioral health disorders. Individually, these symptoms are disabling features of these disorders, causing loss of function. All of the ten cardinal symptoms of brain and behavioral health disorders are difficult to treat because most, if not all, people with brain and behavioral disorders suffer from more than one cause of these symptoms. In real clinical practice, the cause of a symptom could be due to neurology, psychiatry, and/or psychological factors. However, patients seek independent treatment for their symptoms. Anxiety, depression, and psychosis are typically treated by a psychiatrist. Headache, pain, and cognitive difficulty is often treated by a neurologist. Irritability, apathy, insomnia and fatigue are often treated by psychologists or primary care doctors. Anxiety is an example of a symptom that is disabling, difficult to treat and multifactorial. Somatic anxiety (hypersensitivity to stimulation) is an example of a neurological cause of anxiety, often related to migraine. Excessive shyness is an example of a psychological cause of anxiety, often related to social phobia. Excessive worry is an example of a psychiatric cause of anxiety, often related to generalized anxiety disorder or obsessive-compulsive disorder. Despite the fact that the ten cardinal disabling symptoms (i.e., anxiety, apathy, cognitive difficulty, depression, fatigue, headache, insomnia, irritability, pain (e.g., body pain), and psychosis) of brain and behavioral health disorders, in real clinical practice, are multi-factorial, current FDA-approved treatments typically target one component of a disorder at a time. For example, selective serotonin reuptake inhibitors (“SSRI's”), which are the first-line treatment for anxiety disorders, were designed specifically to target serotonergic mechanisms of anxiety. The effectiveness of these medications in and of themselves has proven to be limited. Cognitive behavioral therapy is designed specifically to address psychological components of anxiety. Patients receiving both medication and cognitive behavioral therapy are predicted to have better outcomes than those receiving one targeted treatment or the other. Even with cognitive behavioral therapy and medication, treatment success remains limited, suggesting that neurological underpinnings of anxiety remain untreated in the majority of patients seeking relief for anxiety. No current treatments have been designed to address the multi-factorial features associated with the most disabling symptoms of brain and behavioral health disorders. Accordingly, new treatments that address brain and behavioral health disorders and their symptoms are urgently needed. SUMMARY As described below, the present invention features compositions and methods for treating brain and/or behavioral health disorders and their associated symptoms. The invention provides novel combination therapies comprising an agent that targets the adrenergic system (e.g., anipamil, devapamil, falipamil, gallopamil, tiapamil, and verapamil) and an agent that targets the renin angiotensin aldosterone system (RAAS) (e.g., candesartan, telmisartan). While such agents have been individually approved by the FDA for the treatment of cardiovascular disease, they have not previously been combined, nor have they been used for the treatment of any brain and/or behavioral health disorder. In an embodiment, the invention provides a combination therapy featuring a first agent selected from one or more of anipamil, devapamil, falipamil, gallopamil, tiapamil, and verapamil and a second agent selected from one or more of candesartan and telmisartan. Without intending to be bound by theory, the combinations provided herein create novel, synergistic, equilibrating effects on whole brain cerebral blood flow via modulation of stress-induced hormones in both the body and brain. These combinations are effective in treating brain and/or behavioral health disorders, and their associated symptoms, including but not limited to anxiety, apathy, cognitive difficulty, depression, fatigue, headache, insomni