ProNoxis Research

Our mission is to develop a suitable drug for oral administration in human patients suffering from autoimmune inflammatory disease.

Autoimmune diseases are characterized by an immune system response against the own body, caused by a failure to down-regulate a response against pathogens and/or a failure to discriminate between foreign pathogens and self. The autoimmune reaction leads to chronic inflammation. There are many different forms of autoimmune disorders, affecting various parts of the body. For instance, diabetes affects the pancreas, multiple sclerosis the central nervous system, and rheumatoid arthritis the cartilage of peripheral joints.

Today autoimmune diseases are treated with anti-inflammatory or immune-modulatory drugs. ProNoxis targets a specific mechanism for activation of NOX2, for release of Reactive Oxygen Species (ROS) from phagocytic cell populations.

In developing NOX2-activating drugs, ProNoxis aims at a totally new mechanism for inhibiting and treating autoimmune disease. Due to errors in self-recognition combined with inflammatory response down-regulation failure, auto-reactive T cells react to self-tissue under autoimmune conditions. NOX2-produced ROS is an important and effective natural mechanism for the immune system to control the inflammatory and autoimmune response. Activation of NOX2 in phagocytic cells dampens the autoreactivity of the T cells, preventing further disease progression. NOX2 is activated by small molecules to produce very short-lived ROS while the dampening effect of ROS on the T cells and the inhibition of the autoimmune response is long-lasting.

Genetic association studies in animal models reveal an important role for NOX2 production of ROS in the pathology of autoimmune diseases, such as rheumatoid arthritis (Olofsson et al. 2003; Hultqvist et. al. 2004). NOX2 production of ROS is also important in other chronic inflammatory disease models, such as models for multiple sclerosis (Hultqvist et al, 2009).

Studies of patients with autoimmune conditions have shown lower capacity of ROS generation by NOX2 in patients with severe multiple sclerosis (Mossberg et al., 2009). The same phenomenon has been shown in the Guillain-Barré syndrome (Mossberg et al., 2007) and is even more pronounced in recurrent Guillain-Barré syndrome (Mossberg et al., 2010).

ProNoxis develops products for the treatment of autoimmune diseases characterized by a large unmet medical need and either large patient populations or high-value niche therapy areas. Our strategic focus is on large markets such as Rheumatoid Arthritis, Multiple Sclerosis, and Inflammatory Bowels Disease. This focus includes possibilities for reaching more specialized niche indications, including peripheral nerve inflammatory conditions like Guillain-Barré syndrome and inflammatory uveitis. Our current project is potentially relevant for the treatment of all diseases caused by immune-mediated chronic inflammation.

At present ProNoxis has identified small-molecule compounds for selective and efficient activation of NOX2. Proof of concept experiments using in vitro systems as well as relevant in vivo models show disease amelioration and prevention of disease progression in both rheumatoid arthritis and multiple sclerosis models.