Imagine living everyday with rashes, extreme fatigue, pain, inflammation and organ deterioration.
This is the reality for many of the 5 million people worldwide with lupus which has no known cure and for which treatment is frequently ineffective, painful, invasive or accompanied by severe side effects.
Hope may come in the form of a little pill.
A new study presented at a meeting of the American Chemical Society, 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.
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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 Dykman, a scientist from global pharmaceutical company Bristol Myers Squibb, who was involved in the study.
The new molecule called afimetoran was developed to improve potency while reducing its interaction with non-target receptors and has been shown in mice to not only prevent lupus-like symptoms, but to also reverse symptoms and bring back mice on the brink of death from the associated organ damage.
“We hadn’t seen that reversal with other mechanisms we had evaluated so we were particularly excited about that finding,” says Dykman.
In more good news, afimetoran appeared to work well alongside corticosteroids in mice.
Corticosteroids are often used to treat inflammation and are a common lupus treatment, despite the risks associated with long-term steroid use such as weight gain, thinning bones, high blood pressure, diabetes and increased risks of infection. Afimetoran may enable lower doses of steroids when used as a combination therapy in treating lupus.
There is also potential that the orally-administered molecule may work for other autoimmune disorders such as psoriasis and arthritis, which are also linked to Toll-like receptors.
As afimetoran undergoes phase 2 clinical trials, other pharmaceutical companies are racing to develop their own treatments – many centred 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.”