Treatment of TLR-4-mediated diseases and conditions with aptamers targeting TLR-4

JP7789563B2Active Publication Date: 2025-12-22MERCK HEALTHCARE KG AUF ACHTEEN
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Patent Information

Application Number
JP2021568390
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2019-05-27
Filing Date
2020-05-16
Publication Date
2025-12-22
Estimated Expiration
2040-05-16

AI Technical Summary

Technical Problem

Current treatments for TLR-4-mediated diseases and conditions are limited in their scope and effectiveness, lacking broad-spectrum molecules that can specifically bind to and inhibit TLR-4 to treat a wide range of diseases and conditions associated with TLR-4 overexpression or overactivation.

Method used

Administration of nucleic acid aptamers, specifically targeting the extracellular domain of TLR-4, which are 40 to 100 nucleotides in length and have sequences similar to SEQ ID NOs: 1, 2, 3, and 4, or functionally equivalent variants, to reduce and inhibit TLR-4 activation, thereby ameliorating symptoms of conditions such as acute myocardial infarction and neurodegenerative diseases.

Benefits of technology

The aptamers demonstrate significant reductions in infarct area, fibrosis, necrosis, and axonal damage, improve cardiac function, and reduce demyelination, with potential therapeutic benefits extending to a variety of TLR-4-mediated diseases including myocardial infarction, stroke, multiple sclerosis, and neurodegenerative disorders.

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Abstract

The present disclosure relates to methods of treating, preventing (e.g., suppressing, inhibiting, or delaying), or ameliorating symptoms of a TLR-4-mediated disease or condition, comprising administering an aptamer of the present disclosure to a subject in need thereof, alone or in combination with other pharmacological and / or surgical intervention. In certain embodiments, the aptamer of the present disclosure is administered before, during, or after pharmacological and / or surgical intervention (e.g., thrombolysis such as thrombectomy), or any combination thereof, for the treatment of an ischemic (e.g., myocardial infarction or ischemic stroke), hemorrhagic (e.g., hemorrhagic stroke or hemorrhagic transformation), or neurodegenerative (e.g., multiple sclerosis) disease or condition. The present disclosure also provides specific dosages and administration regimens.
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