A synthetic version of a human protein has been found to alleviate symptoms associated with acute and chronic arthritis in mice, which could be the basis for developing a new drug for the disease, according to researchers. The protein has been found to function by blocking the transmission of chemical signals associated with development of arthritis symptoms.
The idea that the protein, called pre-ligand assembly domain protein or PLAD, might play a role in easing or comforting pain characteristic of rheumatoid arthritis is an incidental discovery. The original work was carried out on a very rare autoimmune disease called autoimmune lymphoproliferative syndrome (ALPS).
Previously, it has been shown that PLAD blocks a cell surface receptor and prevents a needed chemical signaling pathway from functioning correctly. In ALPS, the signal pathway interrupted by PLAD leads to disease symptoms. But, the scientists reasoned, PLAD might also be able to block a related cell surface receptor one involved in passing signals, leading to inflammation. In theory, inhibiting this pathway might benefit people with rheumatoid arthritis, who suffer from excessive inflammation.
The scientists used a variety of techniques to induce arthritis symptoms in mice. Researchers also injected some of the animals with lab-made PLAD (P60 PLAD). It was found that P60 PLAD protein powerfully inhibited the symptoms of TNF-alpha-induced arthritis (a key promoter of inflammation is a chemical called tumor necrosis factor alpha- TNF-alpha). Moreover, it also appeared to inhibit disease symptoms in mice with established as well as acute arthritis. The scientists did not detect any obvious toxicity in the PLAD-treated mice.
The scientist's next aim is to develop a more stable form of P60 PLAD to be followed by testing of the protein in clinical trials. This study opens a new research avenue to better understand and, perhaps, to treat rheumatoid arthritis, according to those who believe that a treatment for rheumatoid arthritis is not far way.