Selective Astrocytic MAGL Inactivation for Alzheimer's Disease Treatment
Summary
USPTO published patent application US20260098268A1 for compositions and methods treating Alzheimer's disease through selective astrocytic MAGL inactivation via AAV-mediated gene silencing. Inventors: Chu Chen, Jian Zhang. Filed September 29, 2023. The invention targets neuroinflammation reduction by selectively inactivating MAGL in astrocytes rather than globally, minimizing adverse effects from neuronal 2-AG degradation disruption.
What changed
USPTO published patent application US20260098268A1 covering compositions and methods for treating Alzheimer's disease through selective inactivation of MAGL (monoacylglycerol lipase) in astrocytes using AAV-mediated gene silencing. The invention addresses limitations of global MAGL inactivation by targeting only astrocytes, thereby reducing neuroinflammation and neuropathology while minimizing functional tolerance and adverse effects associated with neuronal CB1 receptor disruption. The technology provides a targeted therapeutic approach for neurodegenerative diseases.\n\nEntities engaged in biopharmaceutical research, neurological drug development, and gene therapy may benefit from reviewing this patent for freedom-to-operate considerations, licensing opportunities, or competitive landscape analysis. The patent's focus on astrocyte-specific MAGL inactivation represents a differentiated approach in the Alzheimer's therapeutic space.
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Apr 11, 2026GovPing captured this document from the original source. If the source has since changed or been removed, this is the text as it existed at that time.
COMPOSITIONS AND METHODS TO TREAT ALZHEIMER'S DISEASE AND OTHER BRAIN DISEASES
Application US20260098268A1 Kind: A1 Apr 09, 2026
Inventors
Chu CHEN, Jian ZHANG
Abstract
Pharmacological or genetic inactivation of MAGL reduces neuroinflammation and neuropathology in animal models of AD. However, global inactivation of MAGL induces functional tolerance of CB IR, which reduces the effectiveness of pharmacotherapies. Evidence has shown that selective inactivation of MAGL in astrocytes, but not in neurons, reduces neuropathology and synaptic and cognitive impairments in TBI. In particular, results showed that inactivation of astrocytic MAGL attenuates AD neuropathology and prevents deterioration in LTP, spatial learning and memory in AD animals. This shows that neuroprotective effects of global MAGL inactivation largely result from limiting 2-AG degradation in astrocytes, rather than in neurons. Therefore, selective inactivation of astrocytic MAGL provides a better therapeutic outcome for AD, as this greatly minimizes the potential adverse effects resulting from global inactivation-induced disruption of 2-AG degradation in neurons and in other peripheral tissues. To this end, an AAV-mediated gene silencing approach to knock MAGL selectively in astrocytes is presented.
CPC Classifications
C12N 15/1137 A61K 48/0058 C12N 15/86 C12N 2310/14 C12N 2320/32 C12N 2750/14143 C12N 2830/008
Filing Date
2023-09-29
Application No.
19115421
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