Altered peptide ligand (APL) for treatment of rheumatoid arthritis and other autoimmune diseases

Therapeutic area

Goal

To demonstrate the potential usefulness of a peptide type Altered Peptide Ligand (APL) derived from an auto-antigen involved in the pathogenesis of Rheumatoid Arthritis for the treatment of this disease and other autoimmune pathologies.

Description

The CIGB has developed a modified peptide type APL derived from one of the main auto-antigens involved in the pathogenesis of RA, the 60 kDa human heat shock protein (Hsp60). The peptide was designed using Bioinformatics tools and obtained by chemical synthesis. Starting from Hsp60 sequence, a novel region was identified as T cell epitope, which was modified increasing the affinity for HLA-II. The peptide was tested in ex vivo assays using PBMC from RA patients, inducing a substantial increment on the levels of IL-10 (important immuno-regulatory cytokine) and increasing the proliferation of regulatory T cells (CD4+CD25+Foxp3+). There are also evidences that this peptide induces apoptosis in pathogenic clones when the patients are in crisis. In addition, the peptide effect was evaluated in an adjuvant induced arthritis (AA) rat model. Based on the evidence of clinical and histopathological evaluation of the rats and the analysis of the cytokine profile, it was demonstrated that the APL peptide efficiently inhibits the course of RA.

Patent Status

Project Status

Research and proof of concept.

Type of collaboration requested

Preclinical assay. Define the type of cells undergoing apoptosis. Determine the cells producing high levels of IL-10.
Clinical assay in Rheumatoid Arthritis.
To evaluate the applicability of the peptide for the treatment of type I diabetes and juvenile idiopathic arthritis (JIA).

Competitives advantages Milestones

Experience in molecular immunology, bioinformatics and proteomics, highly skilled staff, versatility of the technology.
Milestones to be developed jointly with the partner.

Host Insitutions

BIO/CIGB/2008-14