Cyclodextrin Extraction of Lysosomal Cholesterol
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Solution Overview
Problem
Current treatments for lysosomal storage disorders are inadequate in effectively reducing non-cholesterol lipid and macromolecule accumulation, leading to cellular malfunction and death in affected tissues.
Innovation Solution
Administration of cyclodextrin compounds, either alone or in combination with other therapeutic agents like vitamin E, to promote lysosomal exocytosis and reduce cholesterol accumulation in cells, thereby addressing the underlying lipid and macromolecule accumulation issues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for lysosomal storage disorders are used, then treatment is provided, but non-cholesterol lipid and macromolecule accumulation is not effectively reduced
Solution Approach 1:
The patent extracts and removes accumulated lipids and macromolecules from lysosomes using cyclodextrin compounds. The cyclodextrins form inclusion complexes with cholesterol and other lipids, extracting them from the lysosomal compartment and facilitating their removal from cells, thereby directly addressing the accumulation problem that current treatments fail to resolve.
Solution Approach 2:
Cyclodextrin compounds serve as intermediary agents between the accumulated lipids and the cellular export mechanisms. These compounds mediate the removal process by binding to lipids and macromolecules, transforming them into transportable complexes that can be exported from lysosomes through exocytosis, thus bridging the gap between trapped accumulations and cellular elimination pathways.
2Quantity of substance
If cyclodextrin compounds are administered to reduce lipid accumulation, then cholesterol and macromolecule accumulation is reduced, but treatment complexity increases
Solution Approach 1:
The cyclodextrin compounds exhibit universal applicability across multiple lysosomal storage disorders. The same class of compounds (alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, and their derivatives) can treat different LSDs caused by various enzyme deficiencies, as they address the common downstream pathology of lipid and macromolecule accumulation rather than requiring disorder-specific treatments.
Solution Approach 2:
The patent employs composite therapeutic approaches by combining cyclodextrin compounds with other therapeutic agents. This composite strategy enhances treatment effectiveness while managing complexity, as the cyclodextrins work synergistically with enzyme replacement therapies or other modalities to address both the root cause and the accumulation pathology.
3Reliability
If cyclodextrin compounds are used to promote lysosomal exocytosis, then cellular function is improved, but dosage requirements and administration complexity increase
Solution Approach 1:
The patent optimizes treatment by adjusting key parameters including dosage ranges (0.01-100 mg/kg/day), administration frequency, and cyclodextrin derivative selection. By modifying these parameters, the treatment achieves effective lysosomal exocytosis promotion while minimizing administration complexity and optimizing the balance between therapeutic effect and operational ease.
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 cyclodextrin compounds effectively reduces cholesterol and macromolecule accumulation in lysosomes, improving cellular function and potentially extending lifespan in lysosomal storage disorders, as demonstrated in various disease models.
Implementation Method 1
Cyclodextrins (CD) are sugar molecules in a ring form... beta-cyclodextrin including HPβCD and beta-methyl-cyclodextrin (MβCD) reduced cholesterol accumulation... beta-CD increased exocytosis in primary NPC fibroblasts
Data Source
AI summary
The invention provides for methods of treating lysosomal storage disorders and/or reduction of non-cholesterol lipids, using cyclodextrin compounds, including in combination with other therapeutics, including vitamin E.