Methods and compositions for treating aging-associated impairments
Inventors
Wyss-Coray, Anton • Villeda, Saul A. • Nikolich, Karoly
Assignees
US Department of Veterans Affairs • University of California San Diego UCSD • Leland Stanford Junior University • Alkahest Inc
Publication Number
US-10487148-B2
Publication Date
2019-11-26
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 reducing the 2-microglobulin (B2M) level 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 adult mammal for an aging-associated impairment by reducing the β2-microglobulin (B2M) level in the mammal in a manner sufficient to treat the aging-associated impairment. These methods aim to treat a variety of aging-associated impairments, including cognitive impairments, by lowering B2M levels either systemically or locally within the brain.
Aging is accompanied by structural and neurophysiological changes that result in cognitive decline and vulnerability to neurodegenerative disorders, even though significant neuronal death is not typical. Synapse loss and reduced synaptic plasticity contribute to impaired cognitive function, and aging is the most dominant risk factor for dementia-related diseases such as Alzheimer's disease.
B2M, a component of the class I major histocompatibility complex (MHC I), is found in systemic circulation and is elevated with age. Elevated B2M levels have been linked to negative effects including impaired hippocampal-dependent cognitive function and reduced adult neurogenesis. Hence, the problem being solved is providing means to treat aging-associated impairments, particularly cognitive decline, by reducing B2M levels to counteract its pro-aging effects.
Claims Coverage
The patent claims include one independent claim defining a method of treating aging-associated cognitive impairment by removing B2M from blood and returning depleted blood to the adult mammal. The main inventive features relate to extracorporeal removal of B2M from blood and use in treating cognitive impairment associated with aging.
Method of treating aging-associated cognitive impairment by extracorporeal B2M removal
A method of treating an adult mammal for aging-associated cognitive impairment comprising: obtaining blood from the mammal; extra-corporeally processing the blood to remove β2-microglobulin (B2M); and returning the B2M-depleted blood to the mammal in a manner sufficient to treat the cognitive impairment.
Application to primates and elderly humans
The method is specified for use in primates, particularly humans, including elderly humans aged 60 years or older.
The claims cover methods to treat aging-associated cognitive impairment by extracorporeal removal of B2M from blood and reinfusion of B2M-depleted blood, specifically applied to adult mammals such as elderly humans.
Stated Advantages
Reducing B2M levels ameliorates age-related cognitive and regenerative dysfunction, improving hippocampal-dependent learning and memory.
Targeting B2M provides a way to slow, stabilize, or reverse cognitive decline associated with natural aging and aging-related disorders.
Decreasing systemic or local B2M enhances adult neurogenesis and synaptic plasticity in the brain.
Documented Applications
Treatment or prevention of aging-associated cognitive impairments including natural aging cognitive decline (e.g., mild cognitive impairment), and cognitive impairment associated with aging-related neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, glaucoma, myotonic dystrophy, and dementia.
Therapeutic application in elderly adult mammals, particularly humans aged 50 years or older, including those already suffering from or at risk of aging-associated cognitive impairments.
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