About APPA
APPA is a patented, combination oral therapy of two synthetically produced isomers 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, which involves the entire joint.
Given the multiple pathways involved in this disorder, it is unlikely that targeting a single molecule by a specific mechanism will be effective at combating the disease. As with other chronic disorders, the future of osteoarthritis treatment may lie in combination therapy.
APPA [AKL4] is an investigational NFkB and Nrf2 modulator.
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 pathways a robust but fine-tuned NF-κB and Nrf2 response is essential for an appropriate inflammatory response and subsequent resolution.
By regulating the cross-talk between Nrf2 and NF-κB, APPA regulates rather than blocks the immune response without significantly affecting neutrophil host defence mechanisms.