Periodic Systemic Treg Reduction for CNS Disease Treatment
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Solution Overview
Problem
Existing immunosuppressive therapies for neurodegenerative diseases like Alzheimer's disease fail to effectively address neuroinflammation due to the interference of systemic regulatory T cells (Tregs) with the recruitment of inflammation-resolving leukocytes to the CNS, leading to ineffective or detrimental effects on disease pathology.
Innovation Solution
A pharmaceutical composition that transiently reduces systemic immunosuppression by administering a dosage regimen with treatment sessions followed by non-treatment intervals, allowing selective infiltration of anti-inflammatory cells, including Tregs and monocyte-derived macrophages, to sites of neuroinflammation in the CNS.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If continuous immunosuppressive therapy is administered to treat neurodegenerative diseases, then systemic immunosuppression is maintained, but recruitment of inflammation-resolving leukocytes to the CNS is blocked by regulatory T cells
Solution Approach 1:
The patent applies periodic action by administering immunosuppressive therapy in discrete treatment sessions followed by interval sessions of non-treatment, rather than continuous administration. This periodic regimen allows transient reduction of systemic immunosuppression during interval sessions, enabling recruitment of inflammation-resolving leukocytes to the CNS, while maintaining immunosuppression during treatment sessions to control neuroinflammation.
Solution Approach 2:
The patent implements dynamics by making the level of systemic immunosuppression variable over time through alternating treatment and interval sessions. The dosage regimen dynamically adjusts immunosuppression levels - high during treatment sessions to suppress harmful neuroinflammation, and reduced during interval sessions to allow beneficial leukocyte recruitment, thereby adapting the therapeutic effect to different physiological needs.
2Object-affected harmful factors
If anti-inflammatory drugs are administered to reduce neuroinflammation, then inflammatory responses are suppressed, but disease progression is not effectively halted
Solution Approach 1:
The patent applies local quality by creating a differential immune environment - systemic immunosuppression is maintained in the periphery to reduce overall inflammatory responses, while transient reductions during interval sessions allow selective recruitment of inflammation-resolving leukocytes specifically to the CNS. This creates localized anti-inflammatory effects in the brain without requiring continuous systemic immunosuppression.
Solution Approach 2:
The patent uses periodic treatment intervals as an intermediary mechanism to mediate between systemic immunosuppression and local CNS inflammation resolution. The interval sessions act as a temporal intermediary that temporarily reduces systemic Treg-mediated suppression, allowing beneficial leukocytes to infiltrate the CNS and resolve neuroinflammation, thereby bridging the gap between systemic control and local therapeutic effect.
3Object-affected harmful factors
If systemic immunosuppression is continuously maintained to control inflammation, then neuroinflammatory responses are suppressed, but recruitment of inflammation-resolving cells to the brain is inhibited
Solution Approach 1:
The patent employs periodic action with alternating treatment and interval sessions to periodically reduce systemic immunosuppression. During interval sessions, the reduction in Treg-mediated suppression creates windows of opportunity for inflammation-resolving leukocytes to be recruited to the CNS, thereby maintaining productivity of cell recruitment without compromising overall neuroinflammation control achieved during treatment sessions.
Solution Approach 2:
The patent applies partial action by temporarily and partially reducing systemic immunosuppression during interval sessions rather than completely abolishing it. This partial reduction is sufficient to allow recruitment of inflammation-resolving leukocytes to the CNS, while the immunosuppression maintained during treatment sessions ensures that neuroinflammatory responses remain controlled, achieving the desired recruitment effect without excessive immune activation.
Data Source
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AI summary
A pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS that does not include the autoimmune neuroinflammatory disease, relapsing-remitting multiple sclerosis (RRMS), is provided. The pharmaceutical composition is for administration by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session.