Objective: To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy.
Methods: UX001-CL301 was a phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6 g/d or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by upper extremity composite (UEC) score. Key secondary endpoints included change in lower extremity composite (LEC) score, knee extensor strength, and GNE myopathy-Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results.
Results: Eighty-nine patients were randomized (Ace-ER n = 45; placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER -2.25 kg vs placebo -2.99 kg; LSM difference confidence interval [CI] 0.74 [-1.61 to 3.09]; = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) -1.49 (-5.83 to 2.86); knee extension strength -0.40 (-2.38 to 1.58); and GNEM-FAS mobility domain score -0.72 (-2.01 to 0.57). Gastrointestinal events were the most common AEs.
Conclusions: Ace-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy.
Classification Of Evidence: This study provides Class I evidence that for patients with GNE myopathy, Ace-ER does not improve muscle strength compared to placebo.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512882 | PMC |
| http://dx.doi.org/10.1212/WNL.0000000000006932 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Aceneuraminic acid for distal myopathy].
Nihon Yakurigaku Zasshi
January 2025
Department of Neurology, Tohoku University School of Medicine.
Distal myopathy with rimmed vacuoles (GNE myopathy) is an incurable disease that develops after the late teens, progresses slowly, and has no effective treatment. It is inherited in an autosomal recessive manner, and the number of patients in Japan is estimated to be around 400. The causative gene was revealed to be GNE, the rate-limiting enzyme in the sialic acid biosynthesis pathway, and non-clinical studies demonstrated the effectiveness of sialic acid.
View Article and Find Full Text PDFIntroduction: GNE-myopathy is a distal myopathy with adult-onset and initial involvement of anterior leg compartment. A founder effect has been demonstrated for some patients from several large cohorts in different countries.
Methods: In this study, we investigated the allele frequency of the c.
A pilot trial for efficacy confirmation of 6'-sialyllactose supplementation in GNE myopathy: Randomized, placebo-controlled trial.
Mol Genet Metab
November 2024
Department of Neurology, Pusan National University School of Medicine, Busan, Republic of Korea; Department of Neurology and Biomedical Research institute, Pusan National University Yangsan Hospital, Gyeongsangnam-do, Republic of Korea. Electronic address:
Article Synopsis
- GNE myopathy is a rare genetic muscle disorder that leads to weakness in the ankles and muscle degeneration, caused by mutations in the GNE gene that reduce sialic acid production.
- A clinical trial tested a supplement, 6'-sialyllactose (6SL), at doses of 3g and 6g to see if it could improve muscle strength and health, revealing better outcomes in muscle strength and reduced degeneration with the higher dose.
- The latest study involved 11 participants to compare 6SL with a placebo group over 48 weeks, finding no major differences in muscle strength but a significant degeneration in muscle fat measured by MRI, indicating muscle health issues, particularly in the placebo group.
No Evidence of Early Developmental Delay in Juvenile-Onset Huntington's Disease Patients.
Mov Disord Clin Pract
December 2024
Department of Psychiatry, Carver College of Medicine at the University of Iowa, Iowa City, Iowa, USA.
Background: Previous studies suggest that early developmental delay is a common feature of Juvenile-Onset Huntington's disease (JOHD), with highest incidence in those with very high CAG repeats (> 80). However, all reports of developmental delay in JOHD are exclusively based on retrospective review of medical charts. Comprehensive assessment of birth history metrics may provide better insight into the question of early life development in JOHD.
View Article and Find Full Text PDFIncidence, treatment patterns, and mortality for patients with breast cancer during the first year of the COVID-19 pandemic: a population-based study.
Breast Cancer Res Treat
December 2024
Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA.
Purpose: The COVID-19 pandemic created significant disruptions in the diagnosis and treatment of breast cancer (BC). Several public health measures were taken with limited evidence on their potential impact. In this observational study, we sought to compare the incidence of BC, treatment patterns, and mortality during 2020 versus 2018 and 2019.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!