Senolytic Agents Inhibiting Senescent Beta Cell Processes
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Solution Overview
Problem
Current treatments for Type 1 diabetes do not effectively address the role of senescent processes and the SASP phenotype in the progression of the disease, which contribute to beta cell loss and autoimmune destruction.
Innovation Solution
Administration of senolytic agents to disrupt the transition from stress-response senescent phenotype to SASP phenotype in beta cells, selectively removing senescent cells to prevent or reduce the severity of Type 1 diabetes, and ameliorate immune infiltration of islet cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-generated harmful factors
If senolytic agents are administered to selectively kill senescent beta cells, then the harmful SASP secretome is reduced and beta cell function is preserved, but the risk of insufficient beta cell replacement and accelerated beta cell loss increases
Solution Approach 1:
The patent applies the 'Taking out' principle by selectively removing senescent beta cells that produce harmful SASP secretome through senolytic agents. This extraction targets specifically the pathological senescent cells while preserving healthy beta cells, thereby eliminating the harmful factors without compromising overall beta cell function or replacement capability.
Solution Approach 2:
The patent employs an intermediary approach by using senolytic agents as mediators to selectively eliminate senescent beta cells. These agents act as intermediaries between the harmful SASP secretome and the therapeutic outcome, enabling selective removal of pathological cells while maintaining healthy beta cell populations and their regenerative capacity.
2Object-affected harmful factors
If senolytic agents are used to treat Type 1 diabetes, then autoimmune destruction and insulitis are ameliorated, but the underlying genetic and autoimmune etiology remains unaddressed
Solution Approach 1:
The patent applies the 'Blessing in disguise' principle by converting the harmful effect of senescent beta cells (which produce pro-inflammatory SASP secretome that exacerbates autoimmune destruction) into a beneficial therapeutic target. By eliminating these senescent cells, the treatment reduces autoimmune inflammation and insulitis, thereby ameliorating Type 1 diabetes pathology even though the underlying genetic etiology remains.
3Stability of the object's composition
If beta cells undergo age-related senescence, then cell cycle arrest protects against unrestricted proliferation, but cumulative loss of self-replicating capability reduces beta cell numbers and insulin production
Solution Approach 1:
The patent applies the 'Taking out' principle by selectively removing senescent beta cells that have lost self-replicating capability and are producing harmful SASP secretome. This extraction eliminates the pathological accumulation of non-functional cells, thereby preserving overall beta cell numbers and insulin production capacity while maintaining the protective cell cycle control mechanism in healthy cells.
Data Source
AI summary
The inventor of the present disclosure has advantageously elucidated the role of senescent processes in the development of Type 1 diabetes. Genotoxic stress responses, senescence, and acquisition of a SASP condition in beta cells are drivers that progress at-risk individuals to overt Type 1 diabetes. The administration of senolytic agents to at risk individuals selectively removes senescent cells and relieves beta cells from the factors which drive the development of overt Type 1 diabetes. Accordingly, Type 1 diabetes can be prevented in at-risk individuals by the administration of senolytic compositions. Additionally, given the major role of SASP in the development of Type 1 diabetes, the inhibition of SASP factors may be used to prevent Type 1 diabetes.