Abstracto

P140 peptide, a new immunomodulation tool for lupus may have applications in other chronic inflammatory conditions

Sylviane Muller

P140 is a synthetic peptide issued from the U1-70K protein. It was chemically modified and contains a phosphoserine residue at position 140. P140/ Lupuzorâ had no adverse safety signals and met its primary efficacity end points in a multicenter, randomized, placebo- controlled phase IIb study for lupus. A phase III-clinical trial is presently on- going for this suggestion. The medium of action of P140 has been lately illustrated in MRL/ lpr lupus-prone mice. P140 binds HSPA8/ HSC70 chaperone protein, decreases its expression and reduces autophagic flux in B-lymphocytes of peptide- treated MRL/ lpr mice. P140 interferes with a picky form of autophagy called chaperone- intermediated autophagy or CMA. It induces a lower expression class II-MHC motes and alters the donation of peptides to autoreactive T cells, leading to a reduction T and B cells activation and a drop of potentially pathogenic autoantibodies. This process doesn't affect the resistance of mice to a contagious agent. Grounded on this unique medium of action, we anticipated that the peptide could be effective in other pathological conditions in which reduction of CMA exertion would be salutary. This was estimated in several murine models of habitual seditious conditions. These models specially include a rat model of experimental autoimmune neuritis for habitual seditious demyelinating polyradiculoneuropathy, autoimmune-mediated seditious complaint of the supplemental nervous system. Our first results show that P140 peptide can check the course of the complaint and cover treated creatures. These findings give arguments to conclude that P140 peptide might efficiently work in suggestions other than lupus, most particularly in conditions of seditious, habitual conditions. Peptides and peptidomimetics can serve as immunomodulation agents by either blocking the vulnerable response or stimulating the vulnerable response to induce forbearance. Knowledge of B-or T- cell epitopes along with conformational constraints is important in the design of peptide- grounded immunomodulation agents. Work on the conformational aspects of peptides, conflation