Methods and compositions for treating decreased cognitive ability
Inventors
Butler, Andrew Alistair • Farr, Susan • Girardet, Clemence
Assignees
US Department Of Veternas Affairs • St Louis University • US Department of Veterans Affairs
Publication Number
US-11969460-B2
Publication Date
2024-04-30
Expiration Date
2039-06-04
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Abstract
Disclosed are methods and compositions for treating cognitive decline in subjects in need. More specifically, disclosed are methods of administrating exogenous adropin to subjects suffering from, or at risk of, cognitive decline. Also disclosed are subjects who would benefit from such treatment and pharmaceutical acceptable compositions comprising adropin, adropin34-76, and derivatives or variations thereof.
Core Innovation
The invention relates to methods and compositions for treating reduced cognitive ability, specifically using the polypeptide adropin to treat subjects with decreased cognitive ability including age-related dementia. The method involves administering exogenous adropin, adropin34-76, or variants thereof to subjects suffering from or at risk of cognitive decline.
The problem addressed is the pressing health challenge posed by neurodegenerative diseases such as dementia, Alzheimer's disease, and related conditions, compounded by an aging population and metabolic diseases like type 2 diabetes, obesity, and cardiovascular disorders that increase the risk for cognitive decline. Currently, few treatment options exist to delay or prevent such cognitive deterioration, creating an imperative for new clinical interventions.
The inventors discovered that sustained adropin activity in the brain can slow, delay, or prevent the decline in cognitive performance associated with aging. This neuroprotective effect was demonstrated via transgenic mice overexpressing adropin that showed improved cognition and reduced neuroinflammatory markers. The invention also includes pharmaceutical compositions comprising adropin and its derivatives for effective parenteral administration to treat cognitive decline in human subjects and others at risk.
Claims Coverage
The patent contains one independent claim focused on a method for treating age-related cognitive decline using adropin or its peptide fragments with specified dosing and administration protocols.
Method of treating age-related cognitive decline with adropin peptides
Administering an effective amount of the adropin amino acid sequence of SEQ ID NO: 1 or the adropin34-76 peptide fragment amino acid sequence of SEQ ID NO: 2 to subjects diagnosed with age-related cognitive decline exhibiting decreased adropin levels compared to a prior level, wherein the treatment delays or prevents further progression of cognitive decline as measured by standard cognitive functioning tests.
Effective dosing range for adropin administration
Using an effective dosage ranging from 1000 nmol/kg/day down to 1 nmol/kg/day, with preferred doses around 450 nmol/kg/day or 90 nmol/kg/day, administered daily or multiple times per day over periods of two or more weeks or longer.
Parenteral administration routes
Administering adropin or its fragments via parenteral injection including intraperitoneal, subcutaneous, intramuscular, or intravenous routes.
Administration via oligonucleotide encoding adropin sequences
Administering an oligonucleotide that expresses the adropin amino acid sequence or the adropin34-76 peptide fragment as an alternative to direct peptide administration.
Application to human subjects with specific risk factors
Treatment of human subjects diagnosed with mild cognitive impairment or dementia who also have type 2 diabetes or a family history or genes associated with hypercholesterolemia or other metabolic dysregulation disorders, emphasizing a targeted patient population at risk or experiencing cognitive decline.
The claims broadly cover a method of treating age-related cognitive decline by administering effective amounts of adropin peptides or encoding oligonucleotides via specified parenteral routes at defined dosage ranges, particularly targeting human subjects diagnosed with or at risk of dementia and metabolic disorders.
Stated Advantages
Continuous elevated adropin levels in the central nervous system delay or prevent cognitive decline during aging.
Adropin treatment reduces neuroinflammation and oxidative stress, evidenced by reduced inflammatory cytokine expression and decreased stress-activated kinase activity.
The treatment is effective in models of metabolic dysregulation such as hypercholesterolemia and type 2 diabetes, which are risk factors for dementia, indicating protection under these conditions.
Adropin administration improves cognitive performance as demonstrated by improved learning and memory in various behavioral tests in aged subjects.
Documented Applications
Treatment of age-related cognitive decline and dementia in human subjects, including those diagnosed with mild cognitive impairment, hypercholesterolemia, type 2 diabetes, metabolic dysregulation disorders, or advanced age.
Use as a post-operative prophylactic treatment to reduce dementia risk in elderly patients after surgery.
Treatment in laboratory animals, livestock, show animals, and household pets experiencing cognitive decline or at risk thereof.
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