Combination of cotinine plus antioxidant for treatment-resistant depression and correction of astrocytes functional deficit induced by depression and other neuropathological
Inventors
Assignees
Universidad San Sebastian • US Department of Veterans Affairs
Publication Number
US-11260050-B2
Publication Date
2022-03-01
Expiration Date
2038-02-16
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Abstract
The present invention relates to a method of a) treating any of depression induced by chronic stress; depression in a subject afflicted with PTSD; anxiety induced by chronic stress; anxiety in a subject afflicted with PTSD; cognitive impairment induced by chronic stress; altered morphology and/or reduced number of GFAP+ cells in hippocampus and/or frontal cortex induced by chronic stress; working memory impairment in a subject afflicted with PTSD; b) inhibiting or reversing loss of GFAP+ cells in hippocampus and/or frontal cortex induced by chronic stress; c) decreasing consolidation of contextual fear memory in a subject afflicted with PTSD; d) enhancing extinction of fear memory in a subject afflicted with PTSD; or e) increasing calcineurin A expression in a subject afflicted with PTSD using a combination of cotinine and an antioxidant.
Core Innovation
The invention provides methods for treating depression, anxiety, cognitive impairments, altered morphology and/or reduced number of GFAP+ cells in the hippocampus and/or frontal cortex induced by chronic stress or post-traumatic stress disorder (PTSD) by administering a combination of cotinine or its salts and an antioxidant, particularly krill oil. The combination is shown to decrease depressive and anxiety symptoms, improve memory deficits, inhibit or reverse the loss of GFAP+ astrocyte cells, enhance fear extinction, decrease consolidation of fear memory, and increase calcineurin A expression in subjects afflicted with PTSD or chronic stress.
The problem being solved is that current therapies for stress-induced depression often lack efficacy and are associated with many undesirable side effects. There is a need for new drugs or combinations of drugs that effectively treat treatment-resistant depression, anxiety, cognitive impairments, and neuropathological deficits such as astrocyte loss induced by chronic stress and PTSD. The invention addresses these needs by providing a novel therapeutic combination of cotinine and an antioxidant that restores normal astrocyte function and alleviates behavioral and cognitive symptoms associated with these disorders.
Claims Coverage
The patent contains multiple independent claims primarily directed to methods for treating disorders induced by chronic stress using cotinine and krill oil combinations.
Combination therapy of cotinine and krill oil for treating depression and anxiety
Administering a therapeutically effective amount of cotinine, or a pharmaceutically acceptable salt thereof, together with krill oil, to treat disorders induced by chronic stress including depression and anxiety.
Use of krill oil comprising omega-3 fatty acids and antioxidants
The krill oil in the combination comprises omega-3 fatty acids, phospholipids, and/or astaxanthin, with omega-3 polyunsaturated fatty acids specifically including eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA).
Simultaneous or sequential administration of cotinine and krill oil
The method encompasses administering cotinine and krill oil either simultaneously or non-simultaneously, including co-formulated or separate formulations.
Intranasal administration route
Administering cotinine and krill oil via intranasal administration, with cotinine dosed about 100 mg/day to 200 mg/day.
The claims cover the therapeutic application of cotinine combined with krill oil for treating chronic stress-induced disorders, emphasizing the composition of krill oil, administration modes including intranasal delivery, and dosing protocols.
Stated Advantages
The combination of cotinine plus krill oil is more effective in decreasing depressive-like behavior than its components alone.
Intranasal administration of the combination provides fast onset and rapid delivery to the brain, suitable for emergency mental situations.
Treatment with the composition restores astrocyte number and morphology and inhibits neuroinflammation and hippocampal volume reduction induced by chronic stress.
The combination enhances extinction of fear memory and decreases consolidation of contextual fear memory in PTSD models.
Documented Applications
Treatment of depression induced by chronic stress, including major depressive disorder and treatment-resistant depression.
Treatment of anxiety induced by chronic stress and PTSD.
Treatment of cognitive impairments such as working memory deficits induced by chronic stress and PTSD.
Restoration or inhibition of loss of GFAP+ astrocyte cells in the hippocampus and frontal cortex induced by chronic stress.
Decreasing consolidation and enhancing extinction of contextual fear memory in PTSD patients.
Increasing calcineurin A expression in subjects afflicted with PTSD.
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