It is the most common joint disease. Worldwide, osteoarthritis affects 10% of people of all ages. In France, 10 million adults are affected, according to the Foundation for Medical Research. As a reminder, this pathology is characterized by a destruction of the cartilage, “an inflammation of the membrane that lines the inside of the joint (synovial membrane), as well as a remodeling of the bone layer located directly under the cartilage (subchondral bone)”, noted Inserm. Osteoarthritis is manifested by pain and stiffness and sometimes by inflammation and accumulation of fluid in the joint cavity. The latter can lead to a loss of mobility and be very disabling.
GP130, a “vital” immune system receptor
To date, there is no cure for osteoarthritis. Medicines prescribed by doctors can only limit its progression. This is why Canadian and American researchers have tried to find an effective treatment that would allow the cartilage to regenerate. In a study published in the journal Science Translational Medicine, they found that a cell receptor in the immune system, glycoprotein 130 (GP130), signals when antibodies should attack a virus or infection. Thus, it promotes regenerative results or aggravates disease progression.
This receptor recruits white blood cells to launch the offensives. “By trying to solve the problem, the immune system causes even more damage”, because it causes hyper-inflammation of the joints, explained Denis Evseenko, author of the work, in a statement. “But GP130 is a vital receptor. It cannot be inhibited because it is necessary for stem cell health, as well as cardiovascular and immune function”he added.
Osteoarthritis: superior healing capacities following genetic modification
In their research, the scientists suggested that blocking a single GP130 signaling pathway, using either drug or genetic modification, might prevent the hyper-inflammatory response, which is the characteristic of osteoarthritis. To show that it was possible to slow down the process responsible for the inflammation observed in osteoarthritis, the team genetically modified a mouse by replacing one amino acid with another to prevent the activation of a GP130 signaling pathway. .
According to the results, the mouse showed signs of resistance to osteoarthritis. She also showed superior healing and regeneration abilities compared to other mice. For example, instead of healing skin wounds with a scar, the mouse’s skin appeared to completely regenerate, including hair follicles, glands, and other skin substructures. “No white blood cells rushed to the scene and no hyper-inflammation occurred,” clarified Denis Evseenko.
This molecule would reduce joint pain
Next, the authors tested the effectiveness of a drug compound, called “R805/CX-011”, in mice with osteoarthritis. “We saw a profound effect on joint pain, structure and function,” said Denis Evseenko. These positive results allow the researchers to hope that the molecule can be the subject of studies on human beings in the years to come. This year, the team will initiate a clinical trial to test the effectiveness of R805/CX-011 in treating osteoarthritis in patients.