Cyclophilins are proteins that bind to the immunosuppressant cyclosporine and have peptidyl prolyl isomerase (PPI) activity, which catalyzes the isomerization of peptide bonds and facilitates protein folding.
While there are a number of cyclophilin inhibitors in development, these are non-selective between the four commonly screened cyclophilin isoforms A, B, C and D, according to Cypralis which has inked a deal with J&J subsidiary Janssen to target degenerative diseases including CNS degeneration through selective inhibitors of cyclophilin D.
“The objective is to prevent the continuing loss of nerve cells that causes the symptoms observed in diseases such as Alzheimer’s or Parkinson’s disease,” Cypralis’ CEO Simon Kerr told in-Pharmatechnologist.com. “They are unlikely to restore nerve cells that have already been lost.”
Financial terms of the deal have not been divulged, but Kerr said “Cypralis and Janssen teams will be working closely together with scientific inputs coming from both companies.”
Cypralis will undertake the medicinal chemistry and PPIase screening, he added.
The level of interest among drug developers in PPIs - a class of enzymes found throughout nature – has increased significantly over the past few years, according to the firm and there a number of PPIase inhibitors have reached the market, for example cyclosporine, tacrolimus and pimecrolimus, which were originally developed as immunosuppressive agents.
“The pathophysiological mechanism that is targeted by the Cypralis/J&J collaboration is very well validated and is likely to be involved in diseases other than neurology,” Kerr said. “Cypralis aims to exploit this as broadly as possible and is interested to establish collaborations for other chronic inflammatory and degenerative diseases.”