CAR-Engineered Tregs Targeting Pathogenic Proteins in Neurodegeneration
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Solution Overview
Problem
Current treatments for neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS are inadequate, as they primarily focus on symptom relief rather than addressing the underlying causes of neuronal degeneration.
Innovation Solution
The development of chimeric antigen receptors (CARs) expressed in modified regulatory T cells (Tregs) that target aberrant proteins associated with neurodegenerative diseases, combined with neurodegenerative disease-modifying molecules (NDMMs) to promote neuronal survival and inhibit oxidative/inflammatory activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If current treatments for neurodegenerative diseases are used, then symptom relief is provided, but the underlying causes of neuronal degeneration are not addressed
Solution Approach 1:
The patent uses chimeric antigen receptors (CARs) as intermediary molecules that bridge the gap between the immune system and neurodegenerative disease targets. The CARs are designed to specifically recognize and bind to aberrant proteins (such as amyloid-beta, alpha-synuclein, or tau) in the central nervous system, thereby mediating the immune response against these pathogenic proteins without directly contacting them. This intermediary approach enables the treatment to address underlying causes rather than just symptoms.
Solution Approach 2:
The patent employs the body's own immune system, specifically regulatory T cells (Tregs), to fight neurodegenerative diseases. By engineering Tregs to express CARs that target disease-specific proteins, the treatment harnesses the patient's inherent immune mechanisms to recognize and respond to aberrant proteins in the CNS. This self-service approach eliminates the need for external therapeutic agents and leverages the body's natural protective capabilities.
2Reliability
If chimeric antigen receptors targeting aberrant proteins are administered, then the underlying causes of neurodegeneration are addressed, but the complexity of the treatment increases
Solution Approach 1:
The patent creates a universal CAR-Treg platform that can be adapted to target multiple different aberrant proteins associated with various neurodegenerative diseases. The CAR construct design allows for interchangeable antigen-binding domains that can recognize different targets (amyloid-beta in Alzheimer's, alpha-synuclein in Parkinson's, tau in various tauopathies) while maintaining the same underlying mechanism of action. This multi-functionality reduces the need for entirely different treatment approaches for each disease type.
Solution Approach 2:
The patent modifies key parameters of regulatory T cells by engineering them to express chimeric antigen receptors. This involves changing the cellular phenotype and functional properties of Tregs through genetic modification, enabling them to specifically recognize and respond to aberrant proteins in the CNS. The parameter changes include introducing new surface receptors and altering cytokine production profiles to enhance neuroprotective functions.
3Object-affected harmful factors
If modified regulatory T cells are used to target pathogenic proteins, then neuronal survival is promoted, but the manufacturing complexity increases
Solution Approach 1:
The patent performs preliminary engineering of regulatory T cells ex vivo before administration, during which the CAR construct is introduced and the cells are expanded to therapeutic doses. This preliminary action allows for quality control, characterization, and optimization of the cell product before it enters the patient's body. The cells are pre-conditioned to express the desired CAR and produce neuroprotective cytokines, ensuring they are ready to immediately address inflammation and promote neuronal survival upon administration.
Solution Approach 2:
The engineered regulatory T cells are designed to self-expand and self-sustain within the patient's body after administration. These cells can proliferate in response to antigen stimulation and persist long-term, providing continuous neuroprotective effects without requiring repeated infusions. The cells serve themselves by utilizing the patient's physiological environment for their maintenance and expansion, reducing the burden of manufacturing and administration.
Data Source
AI summary
The present disclosure generally relates to novel chimeric antigen receptors (“CARs”), modified regulatory T cells (“Tregs”) expressing such CARs and/or Tregs which are engineered to express neurodegenerative disease modifying molecules, e.g., which express molecules which prevent oxidative/inflammatory activity, or which promote neuronal growth/survival such as nerve growth factors or non-classical neurotrophic factors. The present disclosure also generally relates to compositions containing such modified Tregs, and methods of use thereof as therapeutics, in particular for treating and preventing neurodegenerative diseases and symptoms associated with therewith, and/or for slowing the onset of such neurodegenerative diseases, particularly in persons at risk because of genetic factors or in persons exhibiting early signs of developing such a neurodegenerative disease.