Characterised by distal muscle weakness, GNE myopathy (also known as Nonaka myopathy, hereditary inclusion body myositis, distal myopathy with rimmed vacuoles or quadriceps-sparing myopathy) is caused by abnormalities in the GNE gene, which codes an enzyme involved in sialic acid biosynthesis. To date, only two natural history studies of this disease have been published, one relating to 24 patients followed up over a one-year period, and the other to 38 patients followed up over a 14-month period.
In parallel with its clinical trials conducted on prolonged-release sialic acid supplements, which were unfortunately not successful in GNE myopathy, Ultragenix Pharmaceuticals conducted two non-interventional studies to describe the natural history of the disease. The first of these, published in 2017, helped in particular to establish genotype/phenotype correlations based on data collected from the international GNE myopathy registry.
The second study, conducted between April 2013 and January 2018, involved centres in France, Bulgaria, Canada, the United States and the United Kingdom, with the aim of following up GNE myopathy progression in 101 adults.
The results obtained in 87 participants, and published in January 2021, confirm a slow and gradual decline in muscle strength over three years, with:
- a significant decrease in upper and lower limb muscle strength at 12 months, progressing over years two and three,
- a decrease in manual dynamometer (hand-held dynamometry or HHD) composite scores in the lower extremities (from 34.3 kg at baseline to 29.4 kg at 36 months) and the upper extremities (from 32 kg at baseline to 25.5 kg at 36 months),
- a decrease in the GNEM-FAS (GNE Myopathy – Functional Activity Scale) score, a validated tool to evaluate motor function in GNE myopathy (mobility, upper extremity function and self-administered care); the decline was even more pronounced in cases where the disease was severe at baseline, i.e. in patients able to walk less than 200 metres in the 6-minute walk test,
- free sialic acid or creatine kinase levels that do not seem to be good markers for disease progression.
The measurement tools used in this study seem to be suited to following disease progression, however slow this may be, and may be used in future clinical trials.
