Transferrin-Deferoxamine Complex for Neuroprotection
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Solution Overview
Problem
Current treatments for Hypoxia Inducible Factor (HIF)-related conditions, such as stroke and neurodegenerative diseases, are inadequate in preventing or reversing neuronal damage due to the limitations of available drugs, including short half-life and toxicity issues, necessitating a more effective neuroprotective approach.
Innovation Solution
Administration of a composition comprising transferrin, which may include recombinant, plasma-derived, or chemically synthesized transferrin, potentially combined with iron chelating agents, to enhance neuroprotection by upregulating HIF1-α protein levels and activating the HIF pathway.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If deferoxamine is used as a neuroprotective agent, then neuroprotection against reperfusion damage is improved, but the treatment effectiveness deteriorates due to reduced half-life in plasma
Solution Approach 1:
The patent combines deferoxamine with transferrin to create a composite treatment system. Transferrin serves as a carrier protein that binds deferoxamine, extending its circulation half-life while maintaining neuroprotective activity. This composite approach resolves the contradiction by preserving the neuroprotection effectiveness of deferoxamine while overcoming its short plasma half-life limitation through the synergistic properties of the transferrin-deferoxamine complex
2Reliability
If available drugs are used to prevent or restore neuronal damage, then some neuroprotection is achieved, but the treatment is insufficient due to toxicity and short half-life
Solution Approach 1:
Transferrin acts as an intermediary carrier that delivers deferoxamine to target tissues while reducing its systemic toxicity. The transferrin protein binds deferoxamine in circulation, protecting it from premature degradation and off-target effects, then facilitates its controlled delivery to injured neuronal tissue. This intermediary approach resolves the contradiction by maintaining the neuroprotective efficacy of deferoxamine while reducing its toxicity through the mediating role of transferrin
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 transferrin composition effectively induces HIF1 alpha protein and upregulates neuroprotective genes, providing significant neuroprotection with minimal toxicity, as demonstrated by increased viability and reduced infarct volume in neuronal cells and animal models, while avoiding the drawbacks of existing treatments.
Implementation Method 1
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids
Implementation Method 2
Molecules with iron chelating abilities have been suggested to be HIF pathway activators by blocking the activity of prolyl hydroxylases
Data Source
AI summary
The present invention relates to methods of treatment of Hypoxia Inducible Factor (HIF)-related conditions, and in particular to methods of treatment of HIF-related conditions comprising the administration of a composition comprising transferrins.