The CORMRA project focuses on the pre-clinical development of carbon monoxide-releasing molecules (CO-RMs) for the treatment of rheumatoid arthritis (RA).
CORMs hold the promise of delivering CO in controlled amounts, at specific rates and in a targeted manner to inflamed tissues such as arthritic joints.
Carbon monoxide (CO) has been shown, by several renowned laboratories around the world, to have a number of anti-inflammatory properties which turn it into an exceptionally promising compound against chronic inflammatory diseases such as RA. In its gaseous form CO presents severe restrictions in terms of its use as a drug in a clinical setting, in particular for the treatment of chronic diseases.
The main goals of this project are:
- to select a small number of exceptionally promising CO-RMs for the treatment of RA
- to develop the best formulations for those compounds
- to test their detailed pharmacological and toxicological properties
- arrive at one or more lead candidates for clinical development
With this aim, three different SMEs will join their resources, critical mass and knowledge in the field of CO-RM chemistry, pharmacological testing, in vitro and in vivo disease models, and standardization and validation of assays.
In vivo proof-of-principle has already been obtained for several CO-RMs and for the various properties that make them potentially drug-like and applicable to treat RA. For instance, Alfama has found that various CO-RMs release CO at rates that are compatible with their use in a chronic, systemic disease, and several CO-RMs have been found to release CO only, or preferentially, in situations where there is an abnormal accumulation of reactive oxygen species (ROS), as occurs in the inflamed musculoskeletal joints of RA patients. In addition, various early CO-RMs have shown strong efficacy in a rat model of Adjuvant Arthritis, a common experimental approach to human RA.