HIR-Fab-IDS Composition for Blood-Brain Barrier Enzyme Delivery
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Solution Overview
Problem
Current enzyme replacement therapies for lysosomal storage diseases, such as mucopolysaccharidosis types I and II, are limited by their inability to penetrate the blood-brain barrier, thereby reducing their effectiveness in treating neurological symptoms.
Innovation Solution
A pharmaceutical composition comprising a therapeutic enzyme, such as iduronate-2-sulfatase, conjugated with a Fab fragment of immunoglobulin IgG specific for the insulin receptor (HIR-Fab-IDS) to enhance its transport to lysosomes in various tissues, including nervous tissue cells, maintaining high enzymatic activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a therapeutic enzyme is administered to treat lysosomal storage diseases, then enzyme deficiency is compensated, but the enzyme cannot penetrate the blood-brain barrier
Solution Approach 1:
The patent uses a Fab fragment of an antibody specific to the insulin receptor as an intermediary carrier to transport the therapeutic enzyme across the blood-brain barrier. The Fab fragment binds to the enzyme and facilitates its passage through the barrier, enabling the enzyme to reach neural tissue that was previously inaccessible
Solution Approach 2:
The patent creates a composite structure by conjugating the therapeutic enzyme with a Fab fragment of an antibody. This composite molecule combines the enzymatic function of the enzyme with the target-specific transport capability of the antibody fragment, enabling both blood-brain barrier penetration and therapeutic activity
2Object-affected harmful factors
If the enzyme is conjugated with a Fab fragment to enhance transport, then penetration into nervous tissue is improved, but the molecular complexity increases
Solution Approach 1:
The patent extracts only the essential Fab fragment (antigen-binding fragment) of the antibody, omitting the Fc portion. This extraction provides sufficient transport functionality while reducing unnecessary molecular complexity and potential immunogenicity associated with the complete antibody structure
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 HIR-Fab-IDS compound demonstrates improved penetration into the brain, restoring enzymatic function by 98% and significantly enhancing the therapeutic efficacy for mucopolysaccharidosis type II, increasing life expectancy and quality of life for patients.
Implementation Method 1
conjugated with a Fab fragment of immunoglobulin IgG specific for the insulin receptor (HIR-Fab-IDS) to enhance its transport to lysosomes
Implementation Method 2
The HIR-Fab-IDS compound demonstrates improved penetration into the brain
Data Source
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AI summary
The invention relates to the field of biotechnology, and more particularly to a pharmaceutical composition and a method for the prophylaxis and treatment of a lysosomal enzyme deficiency in a subject, which can be used in medicine. The present invention relates to an HIR-Fab-IDS compound that can be used for the prophylaxis or treatment of a lysosomal enzyme deficiency in a subject suffering from a lysosomal storage disease in the form of mucopolysaccharidosis type II (MPS II), wherein at least one dose of said HIR-Fab-IDS compound is administered to the subject in an amount of from 1 to 12 mg/kg, and further relates to a pharmaceutical composition for use in the prophylaxis or treatment of a lysosomal enzyme deficiency in a subject with the lysosomal storage disease MPS II, wherein the composition contains said HIR-Fab-IDS compound, as well as to a method for the prophylaxis or treatment of a lysosomal enzyme deficiency in a subject with the lysosomal storage disease MPS II, which includes administering at least one dose of said HIR-Fab-IDS compound to the patient.