DNase Treatment for Vaso-Occlusive Crisis in Sickle Cell Disease
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Solution Overview
Problem
Current treatments for vaso-occlusive crisis in sickle cell disease are inadequate, with no specific drugs to prevent or treat the condition, leading to severe pain, hospitalization, and progressive organ damage, and existing therapies like hydroxy-urea are only partially effective and associated with side effects.
Innovation Solution
Administering DNase to dissolve red blood cell aggregates and restore blood flow, using DNase I or other DNases to break down extracellular DNA that contributes to red blood cell aggregation, thereby facilitating tissue reperfusion and reducing the duration of vaso-occlusive crises.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If hydroxy-urea is administered to reduce sickle cell formation, then hemolysis is reduced, but it is only effective in about 40% of patients and carries risks of carcinogenesis and low fertility
Solution Approach 1:
The patent uses DNase as an intermediary enzyme to degrade extracellular DNA that mediates red blood cell aggregation. Instead of directly modifying hemoglobin or forcing fetal hemoglobin re-expression, the treatment targets the DNA intermediary that causes pathogenic aggregation, thereby resolving vaso-occlusive crises without the genetic side effects of hydroxy-urea
Solution Approach 2:
The invention extracts and removes the harmful extracellular DNA from the system by administering DNase that degrades this DNA into smaller fragments. This removes the mediator of aggregation and vaso-occlusion without affecting the underlying genetic mutation or requiring long-term genetic modification
2Reliability
If blood transfusion is performed to treat severe vaso-occlusive crises, then acute symptoms are relieved, but exposure to viral infection and secondary hemochromatosis occurs
Solution Approach 1:
The patent targets extracellular DNA as the intermediary mediator of red blood cell aggregation and vaso-occlusion. By degrading this DNA with DNase, the treatment addresses the root cause of aggregation without requiring blood transfusion, thereby avoiding the harmful effects of transfusion while still achieving relief of vaso-occlusive crises
3Loss of information
If extracellular DNA is present in plasma during vaso-occlusive crisis, then it mediates red blood cell aggregation, but the mechanism remains little understood
Solution Approach 1:
The patent converts the harmful presence of extracellular DNA into a beneficial diagnostic and therapeutic opportunity. By identifying extracellular DNA as the mediator of aggregation, the invention uses DNase to degrade this DNA, transforming the harmful factor into a target for treatment and thereby converting the problem into a solution
Solution Approach 2:
The invention identifies extracellular DNA as the intermediary mediator between hemolysis and red blood cell aggregation. By targeting and degrading this DNA intermediary with DNase, the treatment breaks the pathogenic chain of aggregation and vaso-occlusion, providing both mechanistic insight and therapeutic benefit
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
DNase effectively dissociates red blood cell aggregates, improving blood flow and reducing the severity and frequency of vaso-occlusive crises, potentially shortening hospitalization and minimizing vascular injury, and can be used prophylactically or in combination with other treatments.
Implementation Method 1
Administering DNase to dissolve red blood cell aggregates and restore blood flow, using DNase I or other DNases to break down extracellular DNA that contributes to red blood cell aggregation
Data Source
Figure 1A~1B
Figure 2A~2B
Figure 2C~2D
AI summary
The present invention relates to methods and pharmaceutical compositions for treating vaso-occlusive crises. In particular, the present invention relates to a method of treating a vaso-occlusive crisis in a subject in need thereof comprising administering tot he subject a therapeutically effective amount of agent capable of degrading, destabilizing or depleting the blood-borne extracellular DNA from the blood of the subject.