RARE DISEASE
GNE myopathy
GNE myopathy
GNE myopathy
Synonyms: DMRV, Distal myopathy with rimmed vacuoles, Distal myopathy, Nonaka type, HIBM2, Hereditary inclusion body myopathy type 2, IBM2, Inclusion body myopathy type 2, Nonaka myopathy, Quadriceps-sparing myopathy
Synonyms: DMRV, Distal myopathy with rimmed vacuoles, Distal myopathy, Nonaka type, HIBM2, Hereditary inclusion body myopathy type 2, IBM2, Inclusion body myopathy type 2, Nonaka myopathy, Quadriceps-sparing myopathy
Synonyms: DMRV, Distal myopathy with rimmed vacuoles, Distal myopathy, Nonaka type, HIBM2, Hereditary inclusion body myopathy type 2, IBM2, Inclusion body myopathy type 2, Nonaka myopathy, Quadriceps-sparing myopathy
Drug discovery
7
drugs
With orphan designations
Overview
GNE myopathy is an autosomal recessive distal myopathy caused by biallelic GNE mutations, disrupting sialic acid biosynthesis. It presents in early adulthood (typically 20s–40s) with progressive distal weakness (e.g., foot drop), sparing quadriceps until late stages. Diagnosis relies on genetic testing, muscle biopsy (rimmed vacuoles), and characteristic MRI patterns. Serum CK is normal/mildly elevated. No approved disease-modifying therapies exist globally, though supportive care improves quality of life [1][4][5][9].
Categories: rare genetic diseases, rare hematological diseases, rare inborn errors of metabolism, rare neurological diseases
Research Papers
146 drug discovery papers about GNE myopathy, with 1 first-in-class and 9 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
146 drug discovery papers about GNE myopathy, with 1 first-in-class and 9 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-22 | Nutritional interventions and dietary supplements in muscle diseases: a systematic review.
Medical nutrition therapy significantly impacts cardiovascular risk and overall health, but effects on muscle diseases remain unclear. This systematic review evaluates the safety and efficacy of dietary interventions and supplements on muscle disease outcomes. A multidisciplinary team conducted a PRISMA-guided systematic review registered on PROSPERO. Searches were conducted across multiple databases and screened against pre-specified inclusion criteria. Of 107 full-text articles screened, 51 met inclusion criteria. Most identified interventions used dietary supplements rather than whole dietary approaches. In inflammatory myopathies, creatine (loading dose 20 g/day, maintenance 3 g/day) combined with exercise improved high-intensity functional performance in PM and DM over 6 months. In Duchenne muscular dystrophy, creatine (2-10 g/day for 8-16 weeks) improved maximal voluntary contraction and fatigue resistance. Carbohydrate-rich diets (65% CHO) reduced exercise-related symptoms in McArdle disease, while high-dose creatine (150 mg/kg/day) paradoxically worsened symptoms. Four trials of aceneuramic acid (6 g/day for 48 weeks) in GNE myopathy demonstrated dose-dependent strength improvements, leading to regulatory approval in Japan. High-protein supplementation showed positive trends for muscle preservation in critical illness myopathy. Quality assessment revealed 31% at low risk of bias, 49% with some concerns and 20% at high risk. Evidence for nutritional interventions in muscle diseases remains limited, especially for inflammatory myopathies. The strongest support emerged for mechanistically targeted approaches: creatine with exercise, carbohydrate-rich and ketogenic diets in McArdle disease and sialic acid in GNE myopathy. Future research requires adequately powered multicentre trials with standardized outcomes, with focus on inflammatory myopathies.
2026-07-16 | Impaired Myogenic Differentiation Is a Shared Feature Across Genetic Myopathies
There is a shared hallmark of defective differentiation across genetic myopathies, a process that has been extensively described in Duchenne muscular dystrophy and also observed in Emery–Dreifuss muscular dystrophy. In this article, we broaden the discussion on myopathies associated with differentiation defects, examining their implications in less characterized muscle conditions that can have onset in adulthood, including facioscapulohumeral muscular dystrophy (FSHD), oculopharyngeal muscular dystrophy (OPMD), and myotonic dystrophies (DM), as well as myopathies caused by genetic variants in FHL1, GNE, DES, CAPN3, and members of the HNRNP family. Muscle damage can result from injury, exercise, or disease, necessitating a highly coordinated repair process to restore normal strength and function. Resident satellite cells are activated, differentiate, and fuse with the damaged tissue to facilitate this repair. This overview emphasizes the importance of muscle differentiation in the pathogenesis of myopathies with diverse etiologies and a broad range of underlying molecular mechanisms. These insights highlight differentiation as a potential convergent therapeutic target.
2026-07-06 | Are there any upcoming clinical trials for humans with GNE myopathy?
Upcoming clinical trials for GNE myopathy include a study on UX016 to evaluate its safety and efficacy, as well as potential future studies on ManNAc dosing and aceneuramic formulations.
2026-05-26 | In Vivo Assessment of dbDNA GNEwt/bi-shRNA-GNEM743T Lipoplex for GNE Myopathy: Improved Potency and Safety.
GNE myopathy is an autosomal recessive disease, associated with skeletal muscle deterioration, which afflicts young adults. GNE plays a pivotal role in sialic acid production. Sialic acid acts as a buffer against reactive oxygen species generated during muscle contraction. Increased oxidative stress may relate to muscle atrophy involving patients with GNE myopathy. GNEM743T is the most common mutation leading to GNE myopathy. In our previous work, we demonstrated that a bifunctional plasmid that expresses wild type (wt) GNE and knocks down the GNEM743T mutant improves sialic acid production in vitro. Now, we expand evidence of in vivo activity of the bifunctional plasmid using a DOTAP-Cholesterol delivery vehicle and reduced toxic plasmid components using dbDNA conversion. We demonstrate that IV delivery of dbDNA lipoplex (LPX) in murine and rat models shows safety, increased DNA delivery, and improved RNA expression per LPX in skeletal muscle over non db plasmid at equal dose. Sialic acid protein expression was also shown increased in mouse muscle following IV treatment with dbDNA plasmid (pDNA) GNEwt/bi-shRNA-GNEM743T LPX. These results support further preclinical investigation to justify product IND development towards Phase 1 trial involving patients with GNE myopathy.
2026-04-15 | Profile of Inherited Neuromuscular and Movement Disorders Among Filipinos: A Referral Single-Center Retrospective Study
Background: Neuromuscular and movement disorders comprise a heterogeneous group of acquired and inherited conditions affecting the motor unit and central movement pathways. Genetic data from underserved populations, including Filipinos, remain limited, highlighting the need for population-specific characterization. Objective: To characterize inherited neuromuscular and movement disorders among Filipinos and determine the diagnostic yield and genetic spectrum using next-generation sequencing (NGS). Methods: This referral single-center retrospective study reviewed Filipino patients who underwent genetic testing for suspected inherited neuromuscular and movement disorders. Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Results: Among 85 patients, 24 (28.2%) had pathogenic/likely pathogenic variants, 33 (38.8%) had variants of uncertain significance (VUS) and 28 (32.9%) were negative. Confirmed diagnoses included pediatric cases of limb-girdle muscular dystrophy, Duchenne muscular dystrophy, spinal muscular atrophy and GNE-related myopathy, and adult cases with myofibrillar myopathy, spinocerebellar ataxia and amyotrophic lateral sclerosis. Pathogenic variants involved 26 genes, most commonly SMN1. Conclusion: This NGS-based characterization of inherited neuromuscular and movement disorders in Filipinos showed 28% diagnostic yield and a spectrum comparable to other Asian cohorts. The high rate of VUS underscores the need for family segregation studies and careful genotype–phenotype correlation. This study highlights the critical role of genetic testing in accurate diagnosis and targeted management to improve outcomes for patients with these rare disorders.
2026-07-22 | Nutritional interventions and dietary supplements in muscle diseases: a systematic review.
Medical nutrition therapy significantly impacts cardiovascular risk and overall health, but effects on muscle diseases remain unclear. This systematic review evaluates the safety and efficacy of dietary interventions and supplements on muscle disease outcomes. A multidisciplinary team conducted a PRISMA-guided systematic review registered on PROSPERO. Searches were conducted across multiple databases and screened against pre-specified inclusion criteria. Of 107 full-text articles screened, 51 met inclusion criteria. Most identified interventions used dietary supplements rather than whole dietary approaches. In inflammatory myopathies, creatine (loading dose 20 g/day, maintenance 3 g/day) combined with exercise improved high-intensity functional performance in PM and DM over 6 months. In Duchenne muscular dystrophy, creatine (2-10 g/day for 8-16 weeks) improved maximal voluntary contraction and fatigue resistance. Carbohydrate-rich diets (65% CHO) reduced exercise-related symptoms in McArdle disease, while high-dose creatine (150 mg/kg/day) paradoxically worsened symptoms. Four trials of aceneuramic acid (6 g/day for 48 weeks) in GNE myopathy demonstrated dose-dependent strength improvements, leading to regulatory approval in Japan. High-protein supplementation showed positive trends for muscle preservation in critical illness myopathy. Quality assessment revealed 31% at low risk of bias, 49% with some concerns and 20% at high risk. Evidence for nutritional interventions in muscle diseases remains limited, especially for inflammatory myopathies. The strongest support emerged for mechanistically targeted approaches: creatine with exercise, carbohydrate-rich and ketogenic diets in McArdle disease and sialic acid in GNE myopathy. Future research requires adequately powered multicentre trials with standardized outcomes, with focus on inflammatory myopathies.
2026-07-16 | Impaired Myogenic Differentiation Is a Shared Feature Across Genetic Myopathies
There is a shared hallmark of defective differentiation across genetic myopathies, a process that has been extensively described in Duchenne muscular dystrophy and also observed in Emery–Dreifuss muscular dystrophy. In this article, we broaden the discussion on myopathies associated with differentiation defects, examining their implications in less characterized muscle conditions that can have onset in adulthood, including facioscapulohumeral muscular dystrophy (FSHD), oculopharyngeal muscular dystrophy (OPMD), and myotonic dystrophies (DM), as well as myopathies caused by genetic variants in FHL1, GNE, DES, CAPN3, and members of the HNRNP family. Muscle damage can result from injury, exercise, or disease, necessitating a highly coordinated repair process to restore normal strength and function. Resident satellite cells are activated, differentiate, and fuse with the damaged tissue to facilitate this repair. This overview emphasizes the importance of muscle differentiation in the pathogenesis of myopathies with diverse etiologies and a broad range of underlying molecular mechanisms. These insights highlight differentiation as a potential convergent therapeutic target.
2026-07-06 | Are there any upcoming clinical trials for humans with GNE myopathy?
Upcoming clinical trials for GNE myopathy include a study on UX016 to evaluate its safety and efficacy, as well as potential future studies on ManNAc dosing and aceneuramic formulations.
2026-05-26 | In Vivo Assessment of dbDNA GNEwt/bi-shRNA-GNEM743T Lipoplex for GNE Myopathy: Improved Potency and Safety.
GNE myopathy is an autosomal recessive disease, associated with skeletal muscle deterioration, which afflicts young adults. GNE plays a pivotal role in sialic acid production. Sialic acid acts as a buffer against reactive oxygen species generated during muscle contraction. Increased oxidative stress may relate to muscle atrophy involving patients with GNE myopathy. GNEM743T is the most common mutation leading to GNE myopathy. In our previous work, we demonstrated that a bifunctional plasmid that expresses wild type (wt) GNE and knocks down the GNEM743T mutant improves sialic acid production in vitro. Now, we expand evidence of in vivo activity of the bifunctional plasmid using a DOTAP-Cholesterol delivery vehicle and reduced toxic plasmid components using dbDNA conversion. We demonstrate that IV delivery of dbDNA lipoplex (LPX) in murine and rat models shows safety, increased DNA delivery, and improved RNA expression per LPX in skeletal muscle over non db plasmid at equal dose. Sialic acid protein expression was also shown increased in mouse muscle following IV treatment with dbDNA plasmid (pDNA) GNEwt/bi-shRNA-GNEM743T LPX. These results support further preclinical investigation to justify product IND development towards Phase 1 trial involving patients with GNE myopathy.
2026-04-15 | Profile of Inherited Neuromuscular and Movement Disorders Among Filipinos: A Referral Single-Center Retrospective Study
Background: Neuromuscular and movement disorders comprise a heterogeneous group of acquired and inherited conditions affecting the motor unit and central movement pathways. Genetic data from underserved populations, including Filipinos, remain limited, highlighting the need for population-specific characterization. Objective: To characterize inherited neuromuscular and movement disorders among Filipinos and determine the diagnostic yield and genetic spectrum using next-generation sequencing (NGS). Methods: This referral single-center retrospective study reviewed Filipino patients who underwent genetic testing for suspected inherited neuromuscular and movement disorders. Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Results: Among 85 patients, 24 (28.2%) had pathogenic/likely pathogenic variants, 33 (38.8%) had variants of uncertain significance (VUS) and 28 (32.9%) were negative. Confirmed diagnoses included pediatric cases of limb-girdle muscular dystrophy, Duchenne muscular dystrophy, spinal muscular atrophy and GNE-related myopathy, and adult cases with myofibrillar myopathy, spinocerebellar ataxia and amyotrophic lateral sclerosis. Pathogenic variants involved 26 genes, most commonly SMN1. Conclusion: This NGS-based characterization of inherited neuromuscular and movement disorders in Filipinos showed 28% diagnostic yield and a spectrum comparable to other Asian cohorts. The high rate of VUS underscores the need for family segregation studies and careful genotype–phenotype correlation. This study highlights the critical role of genetic testing in accurate diagnosis and targeted management to improve outcomes for patients with these rare disorders.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
7 orphan drug designations for GNE myopathy.
7 orphan drug designations for GNE myopathy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
aceneuramic acid | small molecules | FDA | 2025-07-03 | — | Nobelpharma Co., Ltd. |
6¿-Sialyllactose (SL) sodium salt | oligonucleotides | FDA | 2025-03-27 | — | NeuraGene, Inc. |
N-acetyl-D-mannosamine monohydrate | small molecules | EMA | 2016-03-21 | — | Leadiant GmbH |
Aceneuramic acid [Kepnetic] | small molecules | EMA | 2015-10-16 | — | Ultragenyx Germany GmbH |
N-Acetylmannosamine (ManNAc) | small molecules | FDA | 2010-04-05 | — | Leadiant Biosciences, Inc. |
GNE plasmid(H001) | gene therapies | FDA | 2010-03-26 | — | HIBM Research Group |
GNE Lipoplex | gene therapies | FDA | 2008-11-13 | — | Gradalis, Inc. |
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