Perispinal Biologic Delivery Bypassing Blood-Brain Barrier
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Solution Overview
Problem
Current medical treatments for brain injuries, such as stroke and traumatic brain injury, are inadequate in addressing chronic neurological and neuropsychiatric deficits, and existing methods fail to effectively deliver biologics like TNF antagonists across the blood-brain barrier for therapeutic benefits.
Innovation Solution
The use of perispinal administration of biologics, specifically TNF antagonists like etanercept, via the vertebral venous system to bypass the blood-brain barrier and deliver therapeutic doses to the cerebrospinal fluid and brain, facilitating improved neurological function and healing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If biologics like TNF antagonists are administered systemically, then therapeutic coverage is achieved, but the blood-brain barrier prevents effective delivery to the brain
Solution Approach 1:
The patent uses the vertebral venous system as an intermediary pathway to deliver biologics to the brain. Instead of direct systemic administration that is blocked by the blood-brain barrier, the biologic is injected into the epidural space where it can enter the vertebral venous system and be transported to cerebral veins, bypassing the barrier indirectly
Solution Approach 2:
The patent changes the dimension of administration from systemic (whole body circulation) to a localized spinal route that accesses the brain through the vertebral venous system. This dimensional shift allows the biologic to reach the brain through an alternative anatomical pathway that avoids the blood-brain barrier restriction
2Reliability
If perispinal administration is used to deliver biologics to the brain, then effective therapeutic delivery is achieved, but the procedure requires precise anatomical targeting
Solution Approach 1:
The patent applies local quality by targeting a specific anatomical region (the epidural space at the lower spine) with the biologic injection. This localized approach concentrates the therapeutic agent where it can most effectively enter the vertebral venous system and be transported to the brain, rather than diffuse systemic distribution
3Reliability
If chronic brain injury treatments are provided, then neurological function improvement is achieved, but existing treatments are inadequate for long-standing deficits
Solution Approach 1:
The patent applies preliminary action by delivering the biologic directly to the cerebrospinal fluid and brain through the vertebral venous system, ensuring the therapeutic agent reaches the target site before chronic damage can progress further. This direct delivery method maximizes the potential benefit even in chronic conditions by providing high concentrations of the biologic at the site of injury
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 method achieves rapid and sustained clinical improvements in neurological function, including reduced spasticity, improved cognition, and motor function, even in patients with long-standing brain injuries, offering a novel and effective route for treating chronic brain injury symptoms.
Implementation Method 1
The vertebral venous system (VVS) is utilized to deliver a biologic into the brain, retina, cranial nerves, and auditory apparatus
Data Source
AI summary
A method of using biologics to treat chronic brain injury or spasticity due to stroke, trauma and other causes. Preferred embodiments include perispinal, parenteral, transepidermal or intranasal use of TNF antagonists. The TNF antagonists include TNF receptor fusion proteins, TNF monoclonal antibodies (mAbs), humanized TNF mAbs, fully human TNF mAbs, chimeric TNF mAbs, domain TNF antibodies, mAB fragments, anti-TNF nanobodies, dominant negative TNF constructs and TNF inhibitory single chain antibody fragments. One of the preferred embodiments of this invention is the perispinal administration of etanercept for treatment of mammals following stroke. The use of Trendelenburg positioning, catheters, pumps, or depot formulations are included.