Blood-Brain Barrier Permeabilization for CAR-T Delivery
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Solution Overview
Problem
The blood-brain barrier (BBB) poses a significant challenge for delivering therapeutic agents to the brain due to its impermeability, limiting the treatment of brain disorders and cancers such as malignant gliomas, as well as other conditions like Parkinson's and Alzheimer's disease.
Innovation Solution
Administration of monoterpene or sesquiterpene compounds, such as perillyl alcohol, to permeabilize the BBB, allowing for the delivery of therapeutic agents like chemotherapeutic agents or immune cells expressing chimeric antigen receptors (CAR-T cells) to treat brain disorders and cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the blood-brain barrier maintains its impermeability to protect the brain, then brain protection from harmful substances is improved, but delivery of therapeutic agents to the brain deteriorates
Solution Approach 1:
The patent applies preliminary action by administering permeabilizing agents (monoterpene or sesquiterpene compounds) before delivering therapeutic agents to temporarily open the blood-brain barrier. This allows therapeutic agents to enter the brain during the transient permeable state, resolving the contradiction between barrier protection and drug delivery
Solution Approach 2:
The patent uses monoterpene and sesquiterpene compounds as intermediary substances that temporarily modify the blood-brain barrier's permeability. These intermediaries facilitate the passage of therapeutic agents without permanently compromising the barrier's protective function, thus resolving the contradiction between protection and delivery
2Reliability
If hydrophilic therapeutic agents are used to treat brain disorders, then treatment effectiveness is improved, but penetration through the blood-brain barrier deteriorates
Solution Approach 1:
The patent applies preliminary action by first administering permeabilizing agents to open the blood-brain barrier, then subsequently administering hydrophilic therapeutic agents. This sequence allows hydrophilic agents that would normally be excluded to penetrate the barrier and reach the brain, resolving the contradiction between treatment effectiveness and barrier penetration
Solution Approach 2:
The patent changes the permeability parameter of the blood-brain barrier temporarily through administration of monoterpene or sesquiterpene compounds. This parameter change allows hydrophilic substances to cross the barrier during the transient permeable state, resolving the contradiction between maintaining barrier integrity and enabling drug penetration
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
Enhances the delivery of therapeutic agents across the BBB, improving treatment efficacy for brain disorders and cancers by increasing drug concentration and survival rates in animal models.
Implementation Method 1
Administration of monoterpene or sesquiterpene compounds, such as perillyl alcohol, to permeabilize the BBB
Data Source
AI summary
The present invention relates to using monoterpene or sesquiterpene to permeabilize the blood brain barrier. The present invention relates to a method of treating a central nervous system (CNS) cancer wherein perillyl alcohol (POH) is administered to a mammal before or concurrently with a therapeutic agent that is a chimeric antigen receptor T-cell (CAR-T cell). The POH and CAR-T cells can be administered by intraarterial injection. The CNS cancer can be a malignant glioma, pilocytic astrocytomas (grade I), meningiomas, metastatic brain tumors, or pituitary adenomas.