Use of cotinine in treating or preventing neurogenesis deficits and enhancing neurogenesis
Inventors
Moran, Valentina Echeverria • Appunn, Doreen
Assignees
US Department of Veterans Affairs • University of South Florida St Petersburg
Publication Number
US-10307411-B2
Publication Date
2019-06-04
Expiration Date
2035-11-02
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Abstract
A method of inhibiting or treating chemotherapy-induced cognitive dysfunction comprising administering a therapeutically effective amount of cotinine to a cancer patient experiencing chemotherapy-induced cognitive dysfunction.
Core Innovation
The invention provides methods for treating stress-related neurogenesis deficiency and chemotherapy-induced cognitive dysfunction by administering therapeutically effective amounts of cotinine, galantamine, or anatabine. The methods include inducing neurogenesis gene expression and treating or preventing chemotherapy-induced memory loss, depression, and weight loss in cancer patients, particularly those undergoing chemotherapy. Cotinine administration modulates neuroinflammation and enhances neurogenesis gene expression such as Vegfa, Errb2, Egf, Gdnf, and Artn in the hippocampus, despite stress conditions.
The problem addressed is the lack of effective therapeutic agents for the neuropsychological side effects of chemotherapy, including cognitive impairment, depressive-like behavior, neuroinflammation, and neurogenesis deficits. Chemotherapy patients often experience cognitive dysfunction, termed “chemobrain,” with symptoms like impaired working memory, attention, and executive function, and are at risk of depression and weight loss. Current treatments for these side effects have limited efficacy or undesirable side effects, and no methods exist to enhance neurogenesis or ameliorate neurogenesis deficits induced by chemotherapy or stress.
Claims Coverage
The patent includes several independent claims focused on methods of reducing chemotherapy-induced cognitive dysfunction, memory loss, depression, and weight loss in cancer patients by administering cotinine.
Method of reducing chemotherapy-induced cognitive dysfunction with cotinine
Administering a therapeutically effective amount of cotinine between about 0.1 mg/kg to about 10 mg/kg to a cancer patient experiencing chemotherapy-induced cognitive dysfunction.
Method of reducing chemotherapy-induced memory loss or depression with cotinine
Administering a therapeutically effective amount of cotinine between about 0.1 mg/kg to about 10 mg/kg to a cancer patient experiencing chemotherapy-induced memory loss or depression, optionally with enhancement of weight recovery.
Method of administering cotinine with chemotherapy
Administering cotinine intramuscularly, intraperitoneally or orally at the same time, before or after administration of a chemotherapeutic agent, by the same or different route as the chemotherapeutic agent.
Method of preventing chemotherapy-induced memory loss or depression with cotinine
Administering a therapeutically effective amount of cotinine between about 0.1 mg/kg to about 10 mg/kg to a cancer patient prior to chemotherapy or prior to onset of chemotherapy-induced memory loss or depression, including maintaining or reducing chemotherapy-induced weight loss or gain.
The independent claims collectively cover therapeutic methods employing cotinine administration at specified dosages and routes to treat or prevent chemotherapy-induced cognitive dysfunction, memory loss, depression, and weight loss, including co-administration with chemotherapeutic agents.
Stated Advantages
Cotinine provides a dual neurological effect, diminishing both depressive behavior and cognitive impairment.
Cotinine has a low toxicity profile compared to currently used antidepressants and cognitive enhancers.
Cotinine promotes restorative cerebral changes by decreasing neuroinflammation and facilitating brain plasticity.
Cotinine enhances neurogenesis and positively modulates neurogenesis gene expression during stress and neurodegenerative conditions.
Cotinine improves working memory performance and induces faster weight recovery in chemotherapy-treated subjects.
Cotinine is not carcinogenic and does not promote tumor development in tested animal models.
Documented Applications
Treating chemotherapy-induced cognitive dysfunction in cancer patients.
Treating or preventing chemotherapy-induced memory loss, depression, and weight loss.
Preventing chemotherapy-induced neuropsychological side effects by administering cotinine prior to chemotherapy.
Enhancing neurogenesis gene expression in cells exposed to stress-related neurogenesis deficiency.
Treatment of stress-related neurogenesis deficiency including neuroinflammation induced by stress.
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