Fusion Antibody BBB Transport via Glucose Receptor Binding
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Solution Overview
Problem
Current methods face challenges in effectively delivering molecules across the Blood Brain Barrier (BBB) to treat brain and central nervous system disorders due to the barrier's restrictive permeability, limiting the treatment of conditions like Hurler's Syndrome and Hunter's Syndrome.
Innovation Solution
The development of kits and methods involving fusion antibodies that bind to receptors on the BBB, such as the insulin receptor, combined with monosaccharides like glucose, to facilitate delivery of therapeutic agents like iduronate 2-sulfatase and alpha-L-iduronidase across the BBB, either alone or with supplemental glucose administration to manage glucose levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the BBB maintains its protective barrier function, then brain protection from harmful molecules is improved, but delivery of therapeutic molecules to the brain deteriorates
Solution Approach 1:
The patent uses glucose as an intermediary substance that exploits the BBB's glucose transporter system. The fusion antibody is designed to bind to glucose transporters on the BBB, using the body's natural glucose uptake mechanism as a mediator to ferry therapeutic enzymes across the barrier without compromising the BBB's protective function.
Solution Approach 2:
The invention changes the chemical parameters of the therapeutic molecule by fusing it to a glucose moiety. This modification allows the large enzyme molecule to mimic glucose's properties, enabling it to pass through the BBB's glucose transport channels which are normally selective for small glucose molecules.
2Productivity
If fusion antibodies are used to deliver therapeutic enzymes across the BBB, then treatment efficacy for CNS disorders is improved, but glucose-related adverse effects worsen
Solution Approach 1:
The patent employs partial action by using a glucose-fusion approach rather than attempting to open the BBB completely. The fusion antibody utilizes only the glucose transporter pathway, a specific partial route through the BBB, avoiding the need for systemic glucose administration that would cause widespread adverse effects while still achieving targeted delivery.
Solution Approach 2:
The fusion antibody design allows the therapeutic molecule to self-deliver across the BBB by exploiting the body's existing glucose transport system. The glucose moiety on the fusion antibody automatically binds to and is transported by the BBB's glucose transporters, eliminating the need for external assistance or invasive procedures to achieve delivery.
3Productivity
If the BBB permeability is increased to allow molecule passage, then therapeutic delivery is improved, but brain protection from harmful substances deteriorates
Solution Approach 1:
The invention segments the approach to BBB crossing by using receptor-mediated transport through specific glucose transporters rather than increasing general BBB permeability. This segmented, targeted approach allows selective passage of the fusion antibody while maintaining the BBB's restrictive barrier properties against other harmful substances.
Solution Approach 2:
The glucose moiety acts as an intermediary that legitimizes the passage of the fusion antibody through the BBB. By coupling the therapeutic enzyme to glucose, the molecule gains access to the BBB's natural glucose transport pathways without needing to compromise the overall barrier integrity, thus maintaining protection while enabling delivery.
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
This approach enables the therapeutic delivery of enzymes across the BBB, potentially treating lysosomal storage disorders by enhancing the permeability of the BBB and managing glucose-related adverse effects.
Implementation Method 1
a structure that binds to a receptor expressed on the blood brain barrier (BBB)... the structure is an antibody... the structure is a fusion antibody
Implementation Method 2
the monosaccharide is glucose... the monosaccharide is dextrose... the structure and the monosaccharide are contained in the same vessel... the monosaccharide ameliorates the hypoglycemia
Data Source
AI summary
Provided herein are compositions, kits, methods and systems related to administering a structure that crosses the blood brain barrier (BBB) along with a monosaccharide, either simultaneously or consecutively. The structure may be, for example an antibody or fusion antibody that binds to an insulin receptor.