Key result
Sialic acid supplementation shows minimal benefit in GNE myopathy, challenging hyposialylation as the sole disease mechanism.
Why the study?
Twenty-five years after identifying the genetic defect in GNE myopathy, accumulating evidence suggests hyposialylation is not the sole pathomechanism, prompting a review of the field and clinical trial strategies.
This review highlights that hyposialylation is not the sole pathomechanism of GNE Myopathy, suggesting a need to re-evaluate future therapeutic trials.
Hyposialylation insufficient to explain GNEM; leaves open identification of additional pathogenic mechanisms.
Twenty-five years after our identification of the genetic defect in GNE Myopathy (GNEM), we review the current state-of-affairs in the research of this unique myopathy. In this narrative review, we describe the clinical aspects of this myopathy, the genetics of this muscle disorder, the biochemistry of the GNE enzyme, and the animal models that have been developed. We critically discuss the accumulating scientific and clinical data that show that hyposialylation cannot be the sole explanation for the disease pathomechanism. The negative or minimal effects of sialic acid supplementation in clinical therapy trials of GNEM call for a re-evaluation of future planned trials. We review the known facts and the current enigmas as well as research controversies in this field. We also discuss the prospects for further basic research, as a reliable animal model of GNEM is lacking, and future genetic therapy of this myopathy.
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Mitrani‐Rosenbaum et al. (2026) conducted a review in GNE Myopathy (GNEM). A review of GNE Myopathy indicates that hyposialylation cannot solely explain the disease pathomechanism and that sialic acid supplementation has shown minimal effects in clinical trials.
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