A pilot trial for efficacy confirmation of 6'-sialyllactose supplementation in GNE myopathy: Randomized, placebo-controlled trial.

GNE myopathy is a rare genetic muscle disorder characterized by initial ankle dorsiflexor weakness and the presence of rimmed vacuoles in muscle histopathology. Biallelic mutations in the GNE gene are causative, leading to reduced production of sialic acid. In our previous clinical trial, we used 6'-sialyllactose (6SL) as a supplement to increase sialic acid levels and compared the effects of 6SL at doses of 3 g and 6 g. The findings from the trial revealed superior outcomes in muscle strength, attenuation of muscle degeneration, and bioavailability in the 6 g group. This trial was planned to complement the lack of placebo arm from the previous trial and to provide more conclusive evidence for therapeutic value of 6SL in GNE myopathy. Of the 11 participants, five were allocated to the 6SL and six to the placebo group after undergoing 12 weeks of pre-study observation and stratified randomization. At every visit with an interval of 12 weeks for 48 weeks, all participants underwent muscle strength measurement, muscle MRI, biochemical evaluations, 6-min-walk test, and completed a questionnaire. No safety concerns arose during the trial period. Muscle strength, excluding hand grip power, did not show a significant difference between the two groups, which is attributed to the lack of pronounced muscle strength decline in both groups. Hand grip power tended to decrease in both groups, and this decline was statistically significant in the placebo group (p = 0.0004). The fat fraction measured by MRI showed the most significant results in the posterior thigh. The increase in fat fraction, indicating muscle degeneration, was statistically significant between the two groups (p = 0.0004). Although no statistically significant differences were observed between the groups in anterior thigh and both anterior and posterior lower leg, a trend of slowed increase in fat fraction was noted in the 6SL group compared to the placebo group starting from 24 or 36 weeks. Resialylation of cell surface glycoconjugate was demonstrated in 6SL group by measuring lectin bindings on peripheral blood monocytes. The GNEM-FAS, used to assess patient-reported outcomes, did not show statistical significance in the total score or any of the three domains. However, the tendency for scores in the self-care and upper extremity domains to rebound after 24 weeks in the 6SL group suggests the potential for long-term benefits. The effect of 6SL on muscle strength appeared to be minimal compared to our previous clinical trial, likely due to the short duration of the study and the inclusion of relatively early-stage patients. However, the changes in fat fraction measured by muscle MRI and the results of biochemical assays are more promising, suggesting potential benefits with long-term administration in the future.