A new study has found promise in a compound which blocks signals from special receptors in the body thought to be involved in the autoimmune response. More specifically, these receptors are proteins which are designed to detect viral RNA, but mount an autoimmune response when they mistake the body’s own RNA as a threat.
Past research has demonstrated mutations in the genes responsible for coding for these so-called “Toll-like receptors 7 and 8” (TLR7 and TLR8) cause lupus, suggesting they could be good drug targets.
“What was missing was an ability to directly block these receptors with small molecules that could be taken orally,” says Alaric Dyckman, a scientist from global pharmaceutical company Bristol Myers Squibb, who was involved in the study.
"With afimetoran, not only could we prevent the development of lupus-like symptoms in mice before their disease onset, but we could actually reverse the symptoms and prevent death in animals that were days or weeks away from succumbing to the disease. We hadn't seen that reversal with other mechanisms we had evaluated, so we were particularly excited about that finding." Dyckman says he believes the combined effects of afimetoran give it the potential to control lupus as well as or better than existing treatments and do so through an oral delivery, as opposed to requiring injection or infusion.
Afimetoran appeared to work well alongside corticosteroids in mice, that means patients might be able to use lower doses of steroids, a mainstay of lupus treatment. Lower doses would be beneficial because steroids have side effects, such as weight gain, thinning bones, high blood pressure and diabetes, as well as an increased risk of infection.
As afimetoran undergoes phase 2 clinical trials, other pharmaceutical companies are racing to develop their own treatments – many centered around blocking the TLR7 and TLR8 proteins. “This is a good thing”, says Dyckman, as lupus is a diverse disease, and “it’s unlikely that any single approach will provide relief for all of the patients out there.”
