OA is a heterogeneous disease: our and other scientists’ experience suggests that patients belong to different subsets corresponding to so-called disease phenotypes. The scientific community is working to clearly identify these phenotypes, to find molecular targets and pathways specific for them (thus characterizing endotypes), and to eventually obtain a true disease-modifying drug. It is indeed possible that a single “magic bullet”, suitable for all OA patients, does not exist and we will have to find drugs that may be different for each phenotype.
The investigation of OA phenotypes (focus on metabolic and inflammatory phenotypes) is the approach we are following at Rottapharm Biotech.
The metabolic OA phenotype is very common and occurs when there is a disruption of metabolic activities in the body, which may lead to obesity. Metabolic OA offers different potential targets for disease modification: adipokines are among the most promising. Adipokines are cytokines secreted by the adipose tissue; they mediate the low-level, chronic inflammatory state of obesity, and insulin resistance. We are in the final phases of optimization of a selective adipokine modulator that is candidate as a disease-modifying drug in metabolic OA.
Inflammatory OA is triggered by an inflammatory reaction. As such, selective anti-inflammatory agents could be disease-modifying in this patient subpopulation. CR10049 is the lead of a series of small molecules with potent activity on undisclosed kinases that play a role in both OA pain (symptom-modifying) and inflammatory joint degeneration (structure-modifying). One such drug would be a major breakthrough in the treatment of inflammatory OA.