CD39 Binding Protein Targeting Activated Platelets
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Solution Overview
Problem
Current treatments for inflammatory neurological diseases like multiple sclerosis are inadequate, with existing medications having modest effectiveness, significant side effects, and limited understanding of the role of platelets in CNS inflammation.
Innovation Solution
Development of a binding protein comprising the extracellular domain of CD39 and a binding region that specifically targets activated glycoprotein GPIIb/IIIa, inhibiting platelet accumulation and reducing neuroinflammation by enriching CD39 at the site of activated platelets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional medications (steroidal medication, immune suppressants, immunotherapy regimens) are administered to treat multiple sclerosis, then the risk of relapses and disease progression is reduced, but the medications have significant side effects and are poorly tolerated
Solution Approach 1:
The patent extracts and targets the specific pathological role of platelets in CNS inflammation, rather than using broad-spectrum immunosuppressants. By isolating and inhibiting the platelet-mediated inflammatory pathway through anti-platelet factors and binding proteins, the treatment achieves disease-modifying effects while avoiding the systemic side effects of conventional immunotherapy.
Solution Approach 2:
The patent introduces binding proteins as intermediary molecules that specifically bind to activated platelets and inhibit their pro-inflammatory functions. These binding proteins act as mediators between the therapeutic goal (reducing neuroinflammation) and the target (platelets), enabling selective inhibition of platelet-mediated inflammation without affecting other immune system functions.
2Reliability
If anti-platelet factors are administered to inhibit platelet accumulation in CNS inflammation, then neuroinflammation is reduced, but the role of platelets in CNS inflammation was not previously well understood
Solution Approach 1:
The patent performs preliminary research to establish the role of platelets in CNS inflammation before developing targeted therapies. By first demonstrating that platelet accumulation contributes to neuroinflammation in EAE models and that anti-platelet factors reduce this inflammation, the patent creates a knowledge foundation that enables subsequent development of more specific binding proteins and therapies.
Solution Approach 2:
The patent uses feedback from preclinical studies (EAE models) to guide therapeutic development. The observation that anti-platelet factors reduce neuroinflammation in animal models provides feedback that validates the platelet-targeting approach, which then informs the design and optimization of binding proteins for clinical translation.
3Reliability
If binding proteins are designed to specifically bind activated glycoprotein GPIIb/IIIa on platelets, then platelet accumulation at inflammation sites is inhibited, but the complexity of the binding protein structure increases
Solution Approach 1:
The binding proteins are constructed by segmenting different functional domains: an extracellular domain of CD39 for platelet targeting and a binding region specific for activated GPIIb/IIIa. This segmentation allows each domain to perform its specific function while maintaining overall protein stability and manufacturability.
Solution Approach 2:
The binding proteins are composite molecules combining the extracellular domain of CD39 with a binding region specific for activated GPIIb/IIIa. This composite structure integrates platelet targeting capability with activated platelet-specific binding, achieving high specificity while using well-characterized protein domains that facilitate manufacturing.
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 binding protein effectively reduces platelet accumulation and neuroinflammation, offering therapeutic benefits with lower doses and minimized side effects, potentially providing a more effective treatment for multiple sclerosis and other inflammatory neurological diseases.
Implementation Method 1
a binding region that specifically binds to activated glycoprotein (GP)IIb/IIIa
Implementation Method 2
inhibiting ligand binding to GPIIb/IIIa
Data Source
AI summary
The present invention provides a method of treating or preventing an inflammatory neurological disease in a subject, the method comprising administering to the subject a protein comprising an extracellular domain of CD39. The present invention also relates to binding proteins comprising an extracellular domain of CD39.