A Drug Already Approved for Rare Friedreich's Ataxia Degrades STING, a Key Driver of Chronic Inflammation in Aging
A Drug Already Approved for Rare Friedreich's Ataxia Degrades STING, a Key Driver of Chronic Inflammation in Aging
Scientists at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, have demonstrated that omaveloxolone, a drug used since 2023 to treat Friedreich's ataxia (a rare inherited disease in which a single gene mutation progressively destroys motor coordination and often damages the heart), binds to the STING protein and forces the cell to dismantle it through its own protein disposal machinery. In aged mice, this silenced the chronic inflammation that smolders in tissues over years. The study was published in Nature Communications on September 17, 2026.
STING is a sensor protein that detects DNA fragments outside the nucleus and mitochondria (a situation that arises after cellular damage, during infection, or with age) and triggers an inflammatory alarm. With age, this signal fails to shut off completely and remains weakly but persistently active: a 2023 study in Nature linked chronic STING activation to inflammation and neurodegeneration during aging. No approved drug that acts directly on STING existed before this work: experimental blockers such as H-151 only prevent the protein from transmitting its signal without affecting the molecule itself. Even partial, dose-controlled suppression of STING has already been shown to extend lifespan in progeria mice more effectively than complete knockout, because the permanent absence of the protein disrupts macrophage balance.
The Chinese team screened a compound library for a substance capable of eliminating STING from cells entirely. The unexpected hit was omaveloxolone itself, the same Friedreich's ataxia drug. Before this work, only one target was known for it: the protein KEAP1, through which the drug activates NRF2, the cell's intrinsic antioxidant defense.
Settling into the base of the STING binding pocket, the drug works as a "molecular crowbar": it prevents the protein from closing, exposes its hydrophobic regions, and lowers its melting temperature. The enzyme HUWE1 recognizes the destabilized STING, tags it with ubiquitin (the cell's disposal tag), and routes it to the proteasome, the cellular protein shredder. When the authors blocked the proteasome, tagged STING accumulated instead of disappearing, confirming that the proteasome is what destroys it. At a concentration of just 118 nanomolar, the average STING level in cells dropped by half, and at a slightly higher dose it fell by nearly 99%. The team was unable to obtain an X-ray structure of the complex despite screening crystallization conditions. The authors consider this indirect confirmation that the destabilized protein is too heterogeneous to form a crystal lattice.
The effect depends on STING degradation specifically, not on general toxicity of the compound: when cells were driven into senescence by irradiation or doxorubicin, omaveloxolone reduced senescence markers, but when the STING gene was knocked out, the protective effect largely disappeared. The same pattern held in mice carrying hyperactive STING (a model of Aicardi-Goutières syndrome, a rare autoinflammatory condition in humans) and in naturally aged 22-month-old mice: injections every other day reduced STING levels and tissue inflammation, while body weight over two months did not differ from controls.
Omaveloxolone activates NRF2 independently of STING; this activation occurs even in cells with the STING gene knocked out. The drug therefore has two independent mechanisms: in cell culture, STING degradation accounts for the bulk of the effect, while in aged mice both mechanisms appear to operate simultaneously.
Omaveloxolone has already completed clinical trials and has been in clinical use for Friedreich's ataxia for more than three years, with a confirmed safety record. This opens a short path to clinical testing of the same drug against a far more widespread problem: chronic age-related inflammation.