Reagents, compositions, and methods for improving the viability and function of cells, tissues, and organs.

Compositions activating heat shock and antioxidant pathways with celastrol analogs and adjuvants enhance cell viability and function in ischemic conditions, addressing poor cell survival and retention, and improving cardiac function by activating protective pathways.

JP7885194B2Active Publication Date: 2026-07-06タルガバイオメディカルインコーポレイテッド
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Patent Information

Application Number
JP2023208559
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2016-06-15
Filing Date
2023-12-11
Publication Date
2026-07-06
Estimated Expiration
2037-06-15

AI Technical Summary

Technical Problem

There is a critical need for potent compounds and methods to improve cell viability and function in ischemic conditions, as existing treatments face challenges with poor cell survival and retention in ischemic tissues, particularly in ischemic cardiomyocytes, and there is a lack of effective pharmacological cardioprotective agents to mitigate ischemia-reperfusion injury.

Method used

The use of compositions containing compounds that activate heat shock reactions, HSP90 inhibition, KEAP-1 inhibition, HSF1 pathway, and NRF2 pathway, along with antioxidants, such as celastrol analogs and adjuvants, to enhance cell and tissue protection and function, including stem cell preconditioning with celastrol to activate pathways like PI3K/Akt and p44/42 MAPK, upregulating protective genes and proteins.

Benefits of technology

These compositions and methods significantly improve cell viability and function under hypoxic and oxidative stress, reduce infarct size, and enhance cardiac function by activating protective pathways, providing a potential therapeutic solution for ischemic injuries.

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Abstract

To provide compounds, compositions, and methods for improving the viability and / or function of cells or for the in vitro, ex vivo or in vivo protection of cells, tissues, grafts, or organs from various damages.SOLUTION: The reagents and compositions are based on activation of the heat shock response and / or the antioxidant response, contain, for example, HSP90 co-factor inhibitor such as Celastrol or Celastrol analogs, and are used alone or in combination with an adjunct agent (e.g. an NRF-2 activator, antioxidant, and the like). Therapeutic enhancement may also include increase in paracrine effector production and signaling. Also described are methods for improving the resistance of cells, tissues, grafts, or organs to damages or stress, such as hypoxic or oxidative stress-induced cell death, and / or for improving the viability and retention of transplanted or transfused cells. Also provided are the therapeutic treatment or prevention of ischemic injury (e.g. myocardial infarct, ischemia / reperfusion injury) and related stressors (hypoxia, oxidative stress, inflammation, sepsis / shock, and the like).SELECTED DRAWING: None
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Citation Information

Patent Citations

  • Compositions and methods for tissue repair

    US20110218143A1

  • Method of modulating HSF-1

    US20110311508A1