Integrin-Binding Polypeptide for Ischemia Reperfusion Injury
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Solution Overview
Problem
Current therapies are inadequate for effectively addressing ischemia reperfusion injury, which leads to conditions such as acute kidney injury and chronic kidney disease, due to the lack of effective animal models and the complex role of innate immune systems in fibrosis progression.
Innovation Solution
The use of a polypeptide that immunospecifically binds to the epitope recognized by mAb107, which inhibits CD11b/CD18 integrin, reducing inflammatory mediators and preventing fibrosis by stabilizing the integrin in its low-affinity state, thereby improving microvascular perfusion and kidney function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used for ischemia reperfusion injury, then treatment is provided, but the therapies are inadequate and fail to effectively address the injury leading to acute and chronic kidney disease
Solution Approach 1:
The patent changes the therapeutic parameter from conventional non-specific anti-inflammatory approaches to targeted integrin inhibition. By using polypeptides that specifically bind to and inhibit CD11b/CD18 integrins, the therapy addresses the specific molecular mechanism driving fibrosis in ischemia reperfusion injury, thereby improving both reliability and adaptability to the complex pathophysiology.
Solution Approach 2:
The patent introduces polypeptides as intermediary molecules that mediate the therapeutic effect by specifically binding to integrins on immune cells. These polypeptides act as intermediaries between the administered therapy and the pathological process, blocking integrin-mediated signaling pathways that lead to fibrosis without completely suppressing the immune system.
2Reliability
If integrin-binding polypeptides are administered early after ischemia reperfusion injury, then fibrosis and kidney failure are reduced, but the timing window for effective treatment is limited
Solution Approach 1:
The patent applies preliminary action by administering the integrin-binding polypeptide before the full development of fibrotic pathology. By treating within the early window (within 5 hours, preferably within 1 hour) after ischemia reperfusion injury, the therapy prevents the activation of integrins and subsequent fibrotic cascades before they become established, thereby achieving high efficacy within a constrained time window.
3Object-affected harmful factors
If integrin inhibition is used to reduce inflammatory mediators, then fibrosis progression is prevented, but the complex role of innate immune systems in fibrosis must be carefully managed
Solution Approach 1:
The patent applies local quality by targeting integrin inhibition specifically to cells expressing CD11b/CD18 integrins, primarily neutrophils and macrophages involved in fibrotic processes. The polypeptides selectively bind to integrins on these specific cell types, allowing localized suppression of harmful inflammatory and fibrotic mediators while preserving other immune functions, thereby managing the complexity of immune system interactions.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The polypeptide effectively reduces fibrosis and kidney failure by inhibiting the initial and secondary inflammatory reactions, promoting functional recovery and reducing the progression to chronic kidney disease in non-human primates.
Implementation Method 1
a polypeptide that immunospecifically binds the epitope recognized by mab107
Implementation Method 2
stabilizing the integrin in its low-affinity state
Implementation Method 3
Antibody to integrins have been developed... that can bind to CD11b in an activation-independent manner
Data Source
AI summary
This disclosure relates to therapeutic use of integrin-binding antibodies.