Chemical cocktails to induce human neuronal aging to accelerate disease modeling and drug discovery.

A culture medium with specific inhibitors induces senescence in human neurons, addressing the challenge of replicating aging phenotypes in stem cell-derived neurons for effective neurodegenerative disease modeling and drug discovery.

JP7888457B2Active Publication Date: 2026-07-13WISCONSIN ALUMNI RES FOUND
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Patent Information

Application Number
JP2022534271
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2019-12-09
Filing Date
2020-12-09
Publication Date
2026-07-13
Estimated Expiration
2040-12-09

AI Technical Summary

Technical Problem

Current methods for modeling neurodegenerative diseases using human pluripotent stem cell-derived neurons are limited by the inability to systematically and reproducibly induce aging phenotypes, which is crucial for accurate disease modeling and drug discovery, and often alter the genetic background or are not scalable.

Method used

A method involving the use of a culture medium containing DNA glycosylase 1 inhibitors, autophagy inhibitors, and HIV protease inhibitors, along with optional sodium butyrate and SCR-7, to induce cellular senescence in human neurons, expressing senescence-related biomarkers such as β-galactosidase, H3k9Me3, and Lap2β, mimicking aging phenotypes.

Benefits of technology

The method generates chemically induced senescent neurons that exhibit age-related features, allowing for more accurate disease modeling and drug screening by maintaining genetic integrity and scalability.

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Abstract

Provided herein are methods and compositions for chemically inducing senescence in neurons, as well as methods for using chemically induced senescent neurons for neurodegenerative disease modeling and drug discovery. The methods involve contacting human neurons with a culture medium containing an inhibitor of DNA glycosylase 1, an autophagy inhibitor, and an HIV protease inhibitor to obtain an in vitro population of senescent neurons within about four days. When the neurons are obtained from patients with neurodegenerative diseases, the chemically induced senescent neurons obtained by these methods recapitulate the cellular and subcellular phenotypes observed in individuals with neurodegenerative diseases.
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Citation Information

Patent Citations

  • AGE-MODIFIED CELLS AND METHODS FOR MAKING AGE-MODIFIED CELLS

    JP2016516427A

  • Small molecule inhibitors of 8-oxoguanine DNA glycosylase-1 (OGG1)

    US20170038365A1