Affinity-Matured Anti-ASIC1a Antibodies for Ischemic Stroke
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Solution Overview
Problem
Current treatments for acidosis and related disorders, such as ischemic stroke, lack effective solutions that target altered ASIC1a activity, which is implicated in these conditions.
Innovation Solution
Development of antibodies or antigen binding fragments that specifically bind to ASIC1a, inhibiting acid-induced currents and calcium influx, thereby addressing the pathological effects of ASIC1a activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for acidosis and ischemic stroke are used, then existing therapeutic options are available, but they lack effectiveness in targeting altered ASIC1a activity
Solution Approach 1:
The patent applies parameter changes by developing antibodies with optimized binding characteristics to ASIC1a. The affinity-matured antibodies exhibit enhanced binding affinity and specificity to ASIC1a, changing the therapeutic parameter from general acidosis treatment to targeted ASIC1a inhibition, thereby improving both reliability and adaptability
Solution Approach 2:
The patent introduces affinity-matured antibodies as intermediary molecules that specifically bind to ASIC1a channels. These antibodies act as mediators between the therapeutic goal and the target protein, blocking acid-induced currents and calcium influx without directly modifying the ASIC1a structure, thus resolving the contradiction between therapeutic effectiveness and targeting capability
2Reliability
If ASIC1a activity is inhibited to treat acidosis, then therapeutic benefit is achieved, but specificity of ASIC1a targeting must be maintained to avoid off-target effects
Solution Approach 1:
The patent applies local quality by designing antibodies that target specific epitopes on ASIC1a subunits. The affinity-matured antibodies exhibit localized binding to particular regions of ASIC1a, ensuring therapeutic benefit while maintaining high binding specificity and avoiding off-target effects on other ASIC isoforms or proteins
Solution Approach 2:
The patent changes the binding parameter through affinity maturation, optimizing the antibodies' interaction with ASIC1a. This results in enhanced specificity and reduced cross-reactivity, allowing therapeutic benefit to be achieved with precise ASIC1a targeting
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 antibodies effectively treat acidosis and related disorders by inhibiting ASIC1a-mediated acid-induced currents and calcium influx, providing a therapeutic approach for conditions like ischemic stroke and other diseases associated with altered ASIC1a activity.
Implementation Method 1
antibodies or antigen binding fragments that specifically bind to ASIC1a
Data Source
AI summary
Provided are immunoglobulin-related compositions (e.g., antibodies or antigen binding fragments thereof) that specifically bind acid-sensing ion channel 1a (ASIC1a) protein and uses of the same. Also provided is a method of administering an effective amount of the anti-ASIC1a antibodies to treat a subject suffering from, or predisposed to, acidosis, or to treat a subject suffering from a disease caused by or related to altered ASIC1a activity and/or signaling, including ischemic stroke and related conditions.