UTRN

About UTRN

UTRN on chromosome 6q24.2 encodes utrophin, an autosomal paralog of dystrophin that shares much of its structure and many of its binding partners, including actin and the dystrophin associated glycoprotein complex. Utrophin is found at the sarcolemma of developing and regenerating muscle fibers, but in mature muscle it is largely restricted to the neuromuscular and myotendinous junctions, while dystrophin occupies the rest of the membrane. It is also expressed in many other tissues, including the brain, lungs, kidney, and blood vessels. The gene was identified in 1989 as a dystrophin related protein. In Duchenne muscular dystrophy, utrophin levels increase in regenerating fibers, providing partial compensation. Mice lacking both dystrophin and utrophin develop a much more severe disease than mice lacking dystrophin alone, and transgenic overexpression of utrophin prevents disease in dystrophin deficient mice, supporting utrophin upregulation as a therapeutic strategy. Because utrophin is made from the intact UTRN gene, its upregulation would be expected to avoid immune responses against a new protein. Ezutromid, a small molecule utrophin modulator, was discontinued after a phase 2 trial in 2018, and other approaches, including gene editing to activate UTRN and delivery of engineered micro utrophin, are being explored.