APL Peptide Composition for Inflammatory Disease Treatment
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Solution Overview
Problem
Current therapies are ineffective in reducing autoantibody levels, neutrophil activation, and protein citrullination, which are key contributors to inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Alzheimer's disease, and fibrosis.
Innovation Solution
A pharmaceutical composition comprising a modified peptide (APL type peptide identified as Seq ID No. 1) derived from human HSP60, combined with sodium acetate buffer at pH 3.9-7.7 and stabilizing sugars like sucrose or trehalose, which modifies the immune response and reduces neutrophil activation and citrullination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used to treat inflammatory diseases, then disease symptoms may be managed, but autoantibody levels, neutrophil activation, and protein citrullination remain high and ineffective
Solution Approach 1:
The patent applies the 'Blessing in disguise' principle by using citrullinated peptides as immunogens to trigger an immune response that paradoxically reduces harmful citrullination and autoantibody production. The harmful citrullinated proteins serve as the basis for creating therapeutic peptides that convert the harmful immune response into a beneficial regulatory effect, decreasing NETosis and autoantibody levels while maintaining tolerance to citrullinated self-proteins.
2Reliability
If the peptide sequence is modified to create APL type peptide, then immune response is modified and therapeutic effect is achieved, but peptide stability and formulation complexity increase
Solution Approach 1:
The patent applies 'Parameter changes' by systematically modifying the peptide sequence parameters (amino acid substitutions, additions, deletions) to create APL type peptides with specific immunological properties. The peptide sequences are engineered with specific modifications compared to wild-type HSP60, such as alterations in the immunogenic region, to achieve the desired therapeutic effect while maintaining stability through controlled sequence variations.
3Reliability
If peptide concentration is increased to enhance immune response, then therapeutic effect improves, but risk of adverse reactions and formulation complexity increases
Solution Approach 1:
The patent applies 'Partial or excessive action' by using low concentrations of APL type peptides (nanomolar to micromolar range) to achieve significant therapeutic effects. Rather than requiring high peptide concentrations to stimulate immune response, the modified peptide sequences exhibit enhanced immunogenicity and regulatory activity at low doses, thereby avoiding adverse reactions while maintaining effective immune modulation and citrullination reduction.
Data Source
AI summary
The invention is relate with a pharmaceutical composition comprising peptide type APL called identified as SEQ ID No. 1, sodium acetate buffer at pH 3.9-4.7; and at least one stabilizing sugar selected from sucrose or trehalose. This pharmaceutical composition is useful for manufacture of a medicament for treating inflammatory diseases related to an increase of neutrophils or citrullination of proteins. These inflammatory diseases include rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), Alzheimer's disease, and hepatic and pulmonary fibrosis. The invention also discloses a method for the treatment of these diseases, through effective therapeutic administration of the pharmaceutical composition of APL-type peptide.