Boosting reactive oxygen species to fight serious disease
When our body is faced with a challenge such as bacteria or cancer, the immune system is activated and toxic elements are produced to fight the invader. This inflammation keeps us healthy, but once the fight is over these toxic species must be eliminated. This process, known as inflammation resolution, is critical. If it doesn’t take place, this can lead to chronic inflammation as the body continues to attack itself. Issues with inflammation resolution are evident in autoimmune or inflammatory diseases. Inflammation resolution depends in part on reactive oxygen species (ROSs), molecules with critical roles in healthy organisms, including through the regulation of inflammation. High concentrations of ROSs are actually damaging to human tissues, so our bodies have evolved ways to control their generation. Yet in certain pathological situations, these systems can malfunction and not enough ROSs are produced. “In some cases, you have a state when these ROSs cannot be generated and inflammation is not resolved,” explains Andriy Mokhir, professor of Organic Chemistry at Friedrich-Alexander University and NeutroCure(opens in new window) project coordinator. Drugs have been developed to induce the generation of ROSs, which aim to resolve this issue. But ROSs can also damage healthy tissue, so creating them all over the body may cause more harm than good. “The trick is to generate ROSs only at the place of chronic inflammation,” says Mokhir. In the EU-funded NeutroCure project, Mokhir and his colleagues developed a solution first developed in 2017, which can generate and amplify ROSs specifically at inflamed areas of the body.
Generating safe ROS amplifiers
The main goal of the project was to design safe ROS amplifiers, based on the 2017 proof of concept demonstrated in cell lines, and one in vivo model. The team synthesised a large library of over 100 compounds, out of which two lead candidates were selected, which they have found produce ROSs in a safe way. “We have confirmed beneficial effects in murine models of acute inflammation and in several arthritis models,” notes Mokhir. These compounds amplify superoxide radicals, hydroxyl radicals and hydrogen peroxide, three ROSs that can all switch off the chronic inflammation response via different mechanisms and are activated at sites where chronic inflammation exists.
Expanding research into NeutroCure compounds
Scientists from the NeutroCure project continue to work on the research and expand it further. One PhD student is working to found a company based on one of the three compounds and aims to develop it further for the treatment of conditions such as arthritis, inflammatory diseases and autoimmune diseases. Another is developing a NeutroCure compound as an anticancer agent. Unexpectedly, NeutroCure researchers discovered that some of their compounds also have antibacterial properties and aim to develop this further too. “So, if everything works well, we will have three directions where this will be developed,” remarks Mokhir. The team already has three patents from the project results.
Moving towards clinical trials
While clinical trials are some way off, this is the eventual goal of the NeutroCure team. “We need to do preclinical studies first, but the big goal is to go to clinics,” adds Mokhir.
