The NORAD-Pumilio Axis: A Natural Brake That May Slow IBM Progression
For people living with IBM, researchers are increasingly finding that the muscle doesn’t just suffer damage — it also fights back. A new study published October 1, 2026 in the Journal of Neuropathology & Experimental Neurology identifies one of those natural defense systems: the NORAD-Pumilio regulatory axis.
What the Researchers Did
Dr. Lingying Tong and colleagues at Nationwide Children’s Hospital and collaborators studied muscle biopsies from people with sporadic IBM (sIBM). They compared samples with mild versus severe disease features and also looked at muscle from people with other conditions (dermatomyositis, vacuolar myopathy) and healthy controls. They also tested the pathway in VCP-A232E mice, a model of hereditary IBM.
What They Found
As IBM became more severe, levels of the long noncoding RNA NORAD and its binding partners Pumilio 1 and Pumilio 2 (PUM1/PUM2) increased in muscle. The researchers observed NORAD-Pumilio complexes forming structures called NP bodies near muscle cell nuclei — a sign the pathway was ramping up in response to stress.
In the mouse model, NORAD and Pumilio expression also rose with age and disease progression. When mice lacking NORAD were crossed into the VCP-A232E background, removing NORAD made the disease worse in a dose-dependent way — more fibers were small, mitochondria were more abnormal, and there was more necrosis, regeneration, and fat replacement. In other words, having less NORAD allowed the disease to progress faster.
The mice also showed that when PUM2 was highly expressed, NORAD levels went up as a compensatory response, suggesting the axis can be turned on to try to contain damage.
What This Means for IBM Patients
This is preclinical/mechanistic research — it doesn’t change treatment today. But it adds to the growing picture that IBM muscle mounts protective responses, and strengthening those responses could be a future therapeutic strategy. The fact that NORAD ramps up as disease worsens suggests it may be a marker of attempted repair, and boosting it (or supporting this pathway) could one day help slow progression.
It also fits with other recent findings showing IBM is driven by a mix of muscle-intrinsic problems and immune activation — the muscle is fighting back, and understanding how could open new doors for treatment.
Where to Learn More
The paper is published in the Journal of Neuropathology & Experimental Neurology (October 1, 2026).
Source
• Tong L, Ozes B, Moss K, et al. "The NORAD-Pumilio regulatory axis in the evolution of inclusion body myositis." J Neuropathol Exp Neurol. 2026 Oct 1;85(10):1164-1174. doi: 10.1093/jnen/nlag041. PMID: 41991167.
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