APPA [AKL4], an investigational NFkB and Nrf2 modulator, is a patented, combination oral therapy of two synthetically produced isomers, both of which are secondary metabolites of plant origin

Progress in osteoarthritis research has resulted in the identification of signaling pathways with potential mechanistic targets. It is evident that osteoarthritis is not solely a disease caused by ‘wear and tear’ of the joint rather a complex interplay between catabolic and anabolic effects of chondrocytes (cells responsible for cartilage formation and repair) and other cells involving the entire joint driven by inflammatory processes. To be effective, an OA treatment needs to target multiple pathways.

NF-κB is a key intracellular messenger that plays a central role in inflammation through its ability to induce transcription of proinflammatory genes.

Nrf2 is a factor that regulates gene transcription of anti-oxidants in thereby reducing damage by the reactive oxidant species (ROS) generated during inflammation.

NF-κB and Nrf2 activity is essential for maintaining coordinated cellular responses to resolve the inflammatory status of the cell/tissue.

In chronic pathologic states such as OA, where there is an imbalance between the Nrf2 and NF-κB transcription factor pathways, a robust but fine-tuned NF-κB and Nrf2 response is essential for an appropriate inflammatory response and subsequent resolution.

By harmonizing the cross-talk between Nrf2 and NF-κB, APPA regulates rather than blocks the immune response, whilst maintaining host defence mechanisms.

The UK regulator MHRA has granted APPA an Innovation Passport (FDA / EMA fast track equivalent).