Frizzled CRD Protein for Bone Mass and Strength
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Solution Overview
Problem
Current treatments for bone diseases such as osteoporosis, osteoarthritis, and malignant tumors-related bone diseases face challenges with side effects and limited effectiveness in increasing bone mass and strength, necessitating a more effective therapeutic agent.
Innovation Solution
A protein comprising the extracellular cysteine-rich domain of Frizzled 1, Frizzled 2, or Frizzled 7 receptors, or their mutants, is used to increase bone mass and strength by promoting bone formation and density, with the protein being administered or expressed in vivo to enhance bone health.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If current treatments for bone diseases are used, then bone mass and strength should be increased, but side effects occur and effectiveness is limited
Solution Approach 1:
The patent extracts and utilizes only the extracellular cysteine-rich domain (CRD) of the Frizzled receptor, which is the functional region responsible for Wnt binding and signal transduction. By isolating this specific domain (amino acid residues 2-287 of human Frizzled 7, or corresponding regions of Frizzled 1 or 2), the invention achieves bone-forming effects without the side effects associated with full-length receptor proteins or conventional bone disease treatments.
Solution Approach 2:
The invention applies local quality by using a truncated version of the Frizzled receptor that retains only the essential CRD region required for bone formation. This localized domain (comprising approximately the first 287 amino acids with 10 conserved cysteine residues) is sufficient to bind Wnt ligands and activate bone-forming pathways, while eliminating unnecessary portions that could cause adverse effects.
2Quantity of substance
If current treatments are used, then some bone formation effect is achieved, but the effectiveness in increasing bone mass is limited
Solution Approach 1:
The invention changes the molecular parameter by using a specifically engineered CRD domain with optimized amino acid sequence (residues 2-287 of Frizzled 7, or 2-284 of Frizzled 1, or 2-287 of Frizzled 2) that exhibits enhanced binding affinity for Wnt ligands. This parameter optimization results in significantly improved bone mass increase compared to conventional treatments, as demonstrated by the substantial increases in bone volume, density, and formation rate observed in the patent.
Data Source
AI summary
This invention relates to a pharmaceutical composition for treatment of a bone disease comprising, as an active ingredient, a protein comprising an extracellular cysteine-rich domain, which is from the Frizzled receptor selected from the group consisting of mammalian animal-derived Frizzled 1, Frizzled 2, and Frizzled 7 and has activity of increasing bone mass, bone density, and/or bone strength, or a mutant of such domain having sequence identity of 85% or higher to the amino acid sequence of the domain and having activity of increasing bone mass, bone density, and/or bone strength, or a vector comprising a nucleic acid encoding the protein.