<b><i>Background:</i></b> Functional outcome measures used to assess efficacy in clinical trials of investigational treatments for rare neuromuscular diseases like Duchenne muscular dystrophy (DMD) are performance-based tasks completed by the patient during hospital visits. These are prone to bias and may not reflect motor abilities in real-world settings. Digital tools, such as wearable devices and other remote sensors, provide the opportunity for continuous, objective, and sensitive measurements of functional ability during daily life. Maintaining ambulation is of key importance to individuals with DMD. Stride velocity 95th centile (SV95C) is the first wearable acquired digital endpoint to receive qualification from the European Medicines Agency (EMA) to quantify the ambulation ability of ambulant DMD patients aged ≥5 years in drug therapeutic studies; it is also currently under review for the US Food and Drug Administration (FDA) qualification. <b><i>Summary:</i></b> Focusing on SV95C as a key example, we describe perspectives of multiple stakeholders on the promise of novel digital endpoints in neuromuscular disease drug development.
The health-related quality of life and emotional distress among mothers of sons with Duchenne or Becker muscular dystrophies (n = 82) were compared to sex- and age group–matched controls (n = 26). Participants self-reported health-related quality of life for themselves and their son(s), emotional distress, and mood/anxiety-related medication. Mothers reported poorer health-related quality of life across all domains of their health-related quality of life, as well as higher levels of emotional distress. Clinically elevated symptoms of anxiety were reported by 39% of mothers. Mothers’ report of poorer health-related quality of life for their son(s) was a significant predictor of worse health-related quality of life and emotional distress for themselves across most domains. Additionally, older age of mothers predicted greater energy/less fatigue and lower levels of anxiety. Results highlight the need for screening emotional distress among mothers, as well as consideration for accessible interventions to improve the psychosocial functioning among these families.
GNE myopathy is an autosomal recessive disorder caused by mutations in the GNE on chromosome 9p1-q1, which encodes the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. GNE myopathy is characterized by adult-onset muscle weakness and atrophy starting from the tibialis anterior, except for quadriceps. The majority of GNE variants (about 80%) are missense mutations scattered through the epimerase and kinase domains. The present study reviewed thirty-four patients with genetically confirmed GNE myopathy conducted from 2003 to 2018. We performed thorough medical history taking with previous inspection results, neurological examination, laboratory tests and electrophysiologic tests. Genomic DNAs were analyzed by direct sequencing and targeted new generation sequencing methods. The median onset age was 23.3 years (range 10 to 44 years) and sex ratio was approximately 1:1.4 (males 14: females 20). 12 patients showed a family history of autosomal recessive pattern. Patients generally presented distal dominant weakness starting from lower to upper extremities. Serum CK levels were normal to 10 times elevated, ranging from 19 to 2610 IU. In 16 patients, rimmed vacuoles were found in 6 cases of muscle biopsy. On muscle imaging, most of the patients showed distal to proximal muscle involvement patterns which are severe on tibialis anterior, sparing quadriceps. 1 case was proximal muscle involvement dominant pattern out of 11 patients. All patients showed myopathic process in electromyography. Through GNE sequence analysis, Cysteine homozygous genotype at codon 44 (C44S) and Valine homozygous genotype at codon 603 (V603L) was presented in 4 and 7 cases. C44S/V603L was the most common in 8 cases. D207V and C.1726_1726 + 3del (causative translation error as c.G1726C) genotype was firstly documented in South Korea. As discussed in recent studies, patients exhibited phenotype diversity associated with GNE mutations. There was lack of correlations between age of onset, disease severity, clinical presentation, and pathologic findings with mutation sites. However, 11 patients showed the atypical GNE myopathy phenotype. Molecular genetic analysis would help to ensure accurate diagnosis, facilitates genetic counseling and further aids in appropriate management of the disease.
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