Method of treating aging-associated cognitive impairment by reducing CCR3
Inventors
Wyss-Coray, Anton • Rando, Thomas A. • Britschgi, Markus • Rufibach, Kaspar • Villeda, Saul A.
Assignees
US Department of Veterans Affairs • Leland Stanford Junior University
Publication Number
US-11912998-B2
Publication Date
2024-02-27
Expiration Date
2031-01-28
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Abstract
Methods of treating an adult mammal for an aging-associated impairment are provided. Aspects of the methods include modulating CCR3, e.g., by modulating eotaxin-1/CCR3 interaction, in the mammal in a manner sufficient to treat the mammal for the aging-associated impairment. A variety of aging-associated impairments may be treated by practice of the methods, which impairments include cognitive impairments.
Core Innovation
The invention provides methods of treating an aging-associated impairment in an adult mammal by modulating CCR3, specifically through modulating the interaction between eotaxin-1 and CCR3. This modulation is performed in a manner sufficient to treat the aging-associated impairment, which includes cognitive impairments. The methods focus on reducing CCR3 activity and thereby ameliorating age-related cognitive decline.
Aging in organisms accompanies structural and neurophysiological changes in the nervous system that lead to cognitive decline and increased susceptibility to neurodegenerative disorders. Although significant neuronal death is typically absent, synapse loss and functional impairment at the synapse occur, negatively impacting cognitive function. Moreover, aging is the major risk factor for dementia-related diseases such as Alzheimer's disease.
The invention addresses the problem of aging-associated cognitive impairments by providing a method to treat these impairments via modulation of CCR3 and its ligand eotaxin-1. This involves reducing active systemic eotaxin-1 or cell surface CCR3 activity to restore or protect cognitive function and synaptic plasticity, thereby combating the detrimental effects of aging on cognition.
Claims Coverage
The patent claims comprise one independent claim with details elaborating methods for reducing CCR3 to treat aging-associated cognitive impairment, with various inventive features concerning mechanisms and agents to reduce CCR3 or its ligand interaction.
Method of treating aging-associated cognitive impairment by reducing CCR3
A method comprising reducing CCR3 in an adult mammal in an amount sufficient to treat for aging-associated cognitive impairment.
Reduction of eotaxin-1/CCR3 interaction
Reducing CCR3 includes reducing the interaction between eotaxin-1 and CCR3 in the mammal.
Reduction of active systemic eotaxin-1
Reducing eotaxin-1/CCR3 interaction is achieved by reducing active systemic eotaxin-1 levels in the mammal.
Use of active systemic eotaxin-1 reducing agents
Administering an effective amount of an active systemic eotaxin-1 reducing agent to reduce active systemic eotaxin-1.
Use of eotaxin-1 binding agents
The active systemic eotaxin-1 reducing agent is an eotaxin-1 binding agent such as an antibody or fragment thereof, or a small molecule that binds eotaxin-1.
Use of eotaxin-1 expression inhibitory agents
Administering agents that inhibit eotaxin-1 expression, including nucleic acid-based agents, to reduce active systemic eotaxin-1.
Reduction of CCR3 activity
Reducing eotaxin-1/CCR3 interaction is alternatively accomplished by reducing CCR3 activity in the mammal.
Use of active CCR3 reducing agents
Administering an effective amount of an active CCR3 reducing agent, such as CCR3 binding agents (antibodies or small molecules) or CCR3 expression inhibitory agents (e.g., nucleic acids).
Applications to specific mammals
The adult mammal treated may be a primate, including humans, particularly elderly humans such as those 60 years or older.
The claim coverage describes a method of treating aging-associated cognitive impairments by reducing CCR3, either by diminishing eotaxin-1/CCR3 interaction or by lowering active CCR3 levels, utilizing binding agents, expression inhibitors, or other means, applicable to adult mammals, including elderly humans.
Stated Advantages
The methods can slow or reduce the progression of aging-associated cognitive decline.
They can stabilize cognitive abilities and prevent further cognitive impairment in individuals at risk or suffering from aging-associated impairments.
The methods can reduce or reverse cognitive impairments, restoring cognitive abilities potentially to youthful levels.
They enhance synaptic plasticity, neurogenesis, and improve learning and memory functions.
Documented Applications
Treating aging-associated cognitive impairment in adult mammals including mild cognitive impairment.
Treatment or prevention of cognitive impairments in aging-associated disorders such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, glaucoma, myotonic dystrophy, vascular dementia, dementia with Lewy bodies, progressive supranuclear palsy, ataxias, multiple-system atrophy, and other neurodegenerative and aging-related conditions.
Slowing progression, stabilizing, reducing, or reversing aging-associated cognitive decline.
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