A new protein engineered to inhibit molecules that cause inflammation not only reduces symptoms of rheumatoid arthritis in mice but also may have potential to reverse the disease’s course. Researchers hope the findings will point toward a new therapy for this crippling and difficult-to-treat disease, which occurs when the immune system attacks the body’s own joints. Even medications that are most successful in halting joint inflammation are effective in only about half of the patients who try them.
Current drugs for rheumatoid arthritis inhibit tumor necrosis factor (TNF), an inflammatory molecule known to play a role in regulating the immune system and one that has been implicated in numerous diseases, from cancer to multiple sclerosis. However, these anti-TNF medications can also increase the risk of cancer, exacerbate other autoimmune conditions, and cost a patient as much as $20,000 per year. The new synthetic protein, described last week online in the journal Science, appears to target TNF in a far more specific fashion and could be produced at a small fraction of the cost.
A group of more than 20 scientists, led by NYU Langone Medical Center rheumatology researcher Chuanju Liu, found that a protein called progranulin binds to TNF receptors and that administering the protein to mice with rheumatoid arthritis reduced or even eliminated their symptoms. Then they determined which fragments of progranulin were responsible for binding to TNF and combined those fragments to engineer a protein that works even better to suppress disease. Mice with mild arthritis appeared to be disease-free after several weeks of regular injections of the modified progranulin, which the researchers dubbed Atsttrin.
“For early, mild arthritis, our molecule can completely prevent inflammation—it somehow reverses disease progression,” Liu says. In mice with a more acute form of the disease, Atsttrin cut symptom severity in half. And, he says, because the protein can be grown in bacteria, rather than mammalian cells, it could be far less costly than current TNF inhibitors.
“The results are really spectacular,” says Paul Anderson, a rheumatology expert at Harvard Medical School and Brigham and Women’s Hospital in Boston, who was not involved in the study. “It looks like [they’ve found] a new pathway for the treatment of inflammatory arthritis.” While results should be approached cautiously, since animal research doesn’t necessarily translate to humans, the new treatment worked better in animals than the best drugs available to patients today, he says. “It provides a really strong foundation for moving on to the next step.”
Liu has cofounded a company to do just that, and he is now a scientific advisor for the startup, called Atreaon, which has licensed his technology from NYU.