Prion Peptide Hemin Binders for Stroke Treatment
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Solution Overview
Problem
Hemin toxicity following hemorrhagic stroke causes brain damage due to elevated hemin levels, which existing methods fail to effectively mitigate.
Innovation Solution
Utilizing isolated amino acid sequences from the N-terminal domain of prion protein (PrPC) to bind hemin, forming chemical bonds and reducing toxic effects, particularly through administering sequences like SEQ ID NOs: 2, 3, 4, 5, and 6, which are effective at various pH levels, including those simulating stroke conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing methods are used to treat hemorrhagic stroke, then standard stroke protocols are applied, but hemin toxicity causes ongoing brain damage
Solution Approach 1:
The patent introduces a hemin-binding agent as an intermediary substance that binds to free hemin molecules in the brain, preventing hemin from exerting its toxic effects on neurons and glial cells. This mediator approach directly addresses the harmful effect of hemin while allowing standard stroke treatment to continue
Solution Approach 2:
The patent converts the harmful presence of hemin into a beneficial therapeutic opportunity by using hemin-binding agents that selectively bind and neutralize toxic hemin while preserving normal physiological functions. The treatment transforms the pathological hemin accumulation into a targetable condition with specific therapeutic interventions
2Stability of the object's composition
If hemin levels are allowed to remain elevated naturally, then normal physiological processes are maintained, but tissue injury and cell death occur
Solution Approach 1:
The hemin-binding agent acts as a mediator that selectively binds to excess hemin without disrupting normal physiological processes. The agent circulates in the brain and preferentially binds to free hemin molecules that are causing toxicity, while leaving hemin bound to functional proteins like cytochromes undisturbed
Solution Approach 2:
The treatment applies local quality control by targeting specifically the pathological accumulation of free hemin in affected brain regions while preserving normal hemin-containing proteins and pathways. The binding agent concentrates in areas with elevated free hemin levels, providing localized therapy where it is most needed
3Loss of time
If standard stroke treatment is administered, then acute brain injury is addressed, but delayed brain damage continues for days and weeks
Solution Approach 1:
The hemin-binding agent provides preliminary protection by being administered early in the stroke course, before delayed brain damage sets in. The agent is present in the brain during the acute phase and continues to bind and neutralize hemin throughout the subacute and chronic phases, preventing the delayed injury that would otherwise occur
Solution Approach 2:
The treatment ensures continuity of useful action by maintaining hemin-binding activity throughout the entire post-stroke period. The agent continues to function over days and weeks, providing ongoing protection against hemin toxicity during the period when delayed brain damage would normally progress
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 amino acid sequences effectively bind hemin, reducing tissue injury and brain damage by neutralizing toxic hemin levels, as demonstrated by fluorescence spectroscopy, surface plasmon resonance, and rat model studies, showing potential in treating conditions like hemorrhagic stroke and traumatic brain injury.
Implementation Method 1
the isolated amino acid sequence is effective for forming one or more chemical bonds with hemin
Implementation Method 2
as demonstrated by fluorescence spectroscopy
Implementation Method 3
surface plasmon resonance
Data Source
AI summary
Methods of using portions of the N-terminal domain of prion protein for binding hemin are disclosed. In a particular embodiment, a method comprises administering at least one isolated amino acid sequence comprising a peptide from the octarepeat region of PrPC to a solution containing hemin, wherein the isolated amino acid sequence is effective for forming one or more chemical bonds with hemin.