CD47 Agonist Peptides for Mononuclear Phagocyte Clearance in AMD
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Solution Overview
Problem
Current treatments for age-related macular degeneration (AMD), particularly the dry form and geographic atrophy, lack effective anti-inflammatory therapies to inhibit the accumulation and activation of mononuclear phagocytes in the subretinal space, leading to chronic inflammation and tissue damage.
Innovation Solution
Development of an agent that activates CD47, specifically a CD47 agonist such as a TSP1 peptidomimetic or activating peptides like 4N1K, PKHB1, and PKT16, which, when combined with a Fas agonist, helps in eliminating mononuclear phagocytes and reducing inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-inflammatory drugs (ciclosporin, glucocorticoids, NSAIDs) are used to treat AMD, then some inflammatory aspects are inhibited, but mononuclear phagocyte accumulation and activation are not effectively controlled, and harmful side effects occur
Solution Approach 1:
Instead of using conventional anti-inflammatory approaches that suppress immune responses, the invention activates CD47 on mononuclear phagocytes to promote their clearance by the retinal pigment epithelium. This inverted approach transforms the therapeutic strategy from suppression to active elimination of the harmful cells.
Solution Approach 2:
The invention introduces CD47 as an intermediary molecule that mediates the interaction between mononuclear phagocytes and the retinal pigment epithelium. By activating CD47, the therapy enables the RPE to recognize and clear accumulated MPs without requiring direct immunosuppression.
2Reliability
If no specific therapy is available for dry AMD, then disease progression continues unchecked, but existing treatments are not applicable due to lack of approved drugs
Solution Approach 1:
The CD47 activation approach is designed to be universally applicable to both wet and dry forms of AMD by targeting the common pathological mechanism of mononuclear phagocyte accumulation that underlies both disease presentations, rather than requiring form-specific therapies.
3Object-affected harmful factors
If mononuclear phagocytes accumulate in the subretinal space, then chronic inflammation develops leading to tissue damage, but the mechanisms driving accumulation are not inhibited by current therapies
Solution Approach 1:
The therapy activates CD47 on mononuclear phagocytes before they can establish chronic inflammation and cause significant tissue damage. By promoting early clearance of accumulated MPs through CD47 activation, the intervention prevents the development of sustained inflammatory damage rather than treating established pathology.
Data Source
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AI summary
The present invention relates to agents activating CD47 and their use in the treatment of inflammation, in particular non-resolving low grade inflammation, characterized by chronic MP infiltration, such as age-related macular degeneration. The present invention also relates to pharmaceutical compositions, medicaments and kits comprising said agents.