Materials and methods for diagnosis, prevention and/or treatment of stress disorders and conditions associated with abeta peptide aggregation
Inventors
Assignees
US Department of Veterans Affairs • University of South Florida St Petersburg
Publication Number
US-9801865-B2
Publication Date
2017-10-31
Expiration Date
2029-09-24
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Abstract
The subject invention concerns materials and methods for treating and/or preventing diseases associated with accumulation of Aβ peptide in neural tissue. The subject invention also concerns materials and methods for treating and/or preventing stress disorders, such as post-traumatic stress disorder (PTSD). In one embodiment, a method of the invention comprises administering a therapeutically effective amount of cotinine, or a pharmaceutically acceptable salt thereof, to a person or animal in need of treatment. The methods of the invention can be used to prevent and/or treat Alzheimer's disease and Parkinson's disease. The subject invention also concerns compositions that comprise cotinine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or adjuvant. The subject invention concerns materials and methods for detecting and diagnosing conditions associated with accumulation of Aβ peptide in neural tissue, such as Alzheimer's disease and Parkinson's disease, using the chemical cotinine.
Core Innovation
The invention concerns materials and methods for treating and/or preventing diseases associated with the accumulation and/or aggregation of Aβ peptide in neural tissue. In particular, the invention provides methods comprising administering a therapeutically effective amount of cotinine, or a pharmaceutically acceptable salt thereof, to persons or animals in need of treatment. These methods are applicable to neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as Down's syndrome and stress disorders including post-traumatic stress disorder (PTSD).
The invention also encompasses compositions containing cotinine and pharmaceutically acceptable carriers, diluents, or adjuvants, as well as methods for detecting, diagnosing, and monitoring conditions associated with Aβ peptide accumulation using detectably labeled cotinine, including radiolabeled cotinine for use in PET or SPECT imaging. The diagnostic methods involve administering labeled cotinine to a subject and determining its level or location in neural tissue to inform diagnosis and monitor disease progression or treatment efficacy.
The background addresses the problem that Alzheimer's disease is characterized by extracellular amyloid plaques mainly comprising aggregated Aβ peptide, with no effective therapeutic agents currently available. The toxic aggregated forms of Aβ peptide, rather than monomeric forms, are implicated in disease pathology. Furthermore, PTSD affects a significant portion of the population and is associated with increased medical morbidity, with tobacco consumption linked to PTSD prevalence. Existing diagnosis of AD is limited and largely retrospective, necessitating better in vivo diagnostic and monitoring tools.
Claims Coverage
The patent includes one independent claim focusing on treating PTSD by administering cotinine.
Method of treating post-traumatic stress disorder by administering cotinine
A method for treating a post-traumatic stress disorder or condition comprising administering an effective amount of cotinine, or a composition comprising cotinine, to a person or animal, thereby enhancing extinction of fear memory and treating the PTSD or condition.
The claims center on using cotinine to enhance fear memory extinction for treating PTSD, capturing the therapeutic administration of cotinine for this condition.
Stated Advantages
Cotinine protects neurons against Aβ toxicity by inhibiting Aβ oligomerization.
Cotinine has neuroprotective activity independent of nicotinic acetylcholine receptors (nAChRs).
Cotinine enhances the extinction of fear memory, thereby aiding in the treatment of PTSD.
Cotinine facilitates serotonin release and modulates neuronal signaling associated with brain plasticity.
The use of cotinine as a diagnostic agent allows for in vivo detection and monitoring of diseases associated with Aβ peptide accumulation by imaging techniques such as PET and SPECT.
Documented Applications
Treatment and prevention of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease through administration of cotinine.
Treatment of Down's syndrome by administering therapeutically effective amounts of cotinine.
Treatment and prevention of stress disorders, including post-traumatic stress disorder (PTSD), by administering cotinine to enhance extinction of fear memory.
Use of detectably labeled cotinine, including radiolabeled forms, for detecting, diagnosing, and monitoring Aβ peptide accumulation in neural tissue for diseases such as Alzheimer's disease and Parkinson's disease via imaging modalities like PET and SPECT.
Methods for identifying and evaluating the efficacy of drugs targeting diseases associated with Aβ accumulation by monitoring changes in labeled cotinine binding.
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