SEMA4D Binding Molecules for Blood-Brain Barrier Integrity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments fail to effectively address the increased permeability of the blood-brain barrier (BBB) in neuroinflammatory disorders, which is associated with SEMA4D signaling, leading to compromised BBB integrity and neuroinflammatory conditions.
Innovation Solution
Administration of specific binding molecules that target SEMA4D, either by inhibiting its interaction with its receptor or increasing Claudin-5 expression, to decrease BBB permeability and treat neuroinflammatory disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If SEMA4D signaling is active, then immune cell activation and neuroinflammatory response are enhanced, but blood-brain barrier integrity is compromised and permeability increases
Solution Approach 1:
The patent extracts and neutralizes the harmful SEMA4D signaling component by administering binding molecules (antibodies) that specifically bind to SEMA4D, preventing it from interacting with its receptor Plexin-B1 on endothelial cells. This removes the pathological effect of SEMA4D without affecting other physiological processes
Solution Approach 2:
The binding molecules act as intermediary agents that intervene between SEMA4D and its receptor Plexin-B1. These antibodies bind to SEMA4D and block its interaction with the receptor, thereby preventing the downstream signaling that leads to BBB disruption while maintaining the ability to treat neuroinflammatory disorders
2Reliability
If current treatments are used for neuroinflammatory disorders, then general inflammation is addressed, but BBB permeability remains unresolved
Solution Approach 1:
The patent applies local quality by targeting the specific mechanism of BBB disruption through SEMA4D signaling rather than using general anti-inflammatory treatments. The binding molecules specifically address the BBB permeability issue by blocking SEMA4D-Plexin-B1 interaction at the endothelial cell level, while other treatments address systemic inflammation
Solution Approach 2:
The patent employs preliminary action by administering binding molecules that prevent SEMA4D from disrupting BBB integrity before neuroinflammatory damage can occur. By blocking the SEMA4D-Plexin-B1 interaction early in the pathological process, the treatment prevents BBB breakdown and subsequent neuronal damage
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 use of SEMA4D binding molecules effectively reduces BBB permeability, thereby treating neuroinflammatory disorders by maintaining or increasing Claudin-5 expression, which enhances the integrity of the blood-brain barrier.
Implementation Method 1
an isolated binding molecule which specifically binds to semaphorin-4D (SEMA4D)
Implementation Method 2
the binding molecule maintains or increases Claudin-5 expression in the subject
Data Source
AI summary
Provided herein are methods for decreasing blood-brain barrier permeability in a subject with a neuroinflammatory disorder, comprising administering to the subject an effective amount of an isolated binding molecule which specifically binds to semaphorin-4D (SEMA4D) or to its high affinity Plexin-B1 receptor.