Blog Archives
Pooled analysis of eteplirsen for Duchenne muscular dystrophy
Eteplirsen has received support from medical experts and parents of affected Duchenne muscular dystrophy children, but the FDA has delayed their decision for approval of this drug. Here, the authors present the results of the first pooled-analysis of previous studies assessing the safety and efficacy of eteplirsen. A total of four relevant clinical studies were … [Read more]
Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase
Glycogen storage disease type II or Pompe disease is a severe neuromuscular disorder caused by mutations in the lysosomal enzyme, acid α-glucosidase (GAA), which result in pathological accumulation of glycogen throughout the body. Enzyme replacement therapy is available for Pompe disease; however, it has limited efficacy, has high immunogenicity, and fails to correct pathological glycogen … [Read more]
Safety and efficacy of drisapersen in ambulant DMD patients
This 48-week, randomised, placebo-controlled phase 3 study (DMD114044; NCT01254019) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years, with Duchenne muscular dystrophy (DMD) resulting from an exon 51 skipping amenable mutation. Drisapersen was generally well tolerated, with injection-site reactions and renal events as most commonly reported adverse events. … [Read more]
Progressive muscle weakness and loss of motor function are characteristic of all SMA types
Natural history studies in SMA have primarily focused on infants and children. Natural history studies encompassing all age groups and SMA types are important for the interpretation of treatment effects of recently introduced SMN augmenting therapies. This cross-sectional study investigated muscle strength, Hammersmith Functional Motor Scale (Expanded) scores and the patterns of muscle weakness … [Read more]
Diaphragmatic AAV gene therapy in early-onset Pompe Disease
This study describes the results of the first in human trial of diaphragmatic gene therapy (AAV1-CMV-GAA) to treat respiratory and neural dysfunction in early-onset Pompe disease. The primary objective was to assess the safety of rAAV1-CMV-hGAA vector delivered to the diaphragm muscle of Pompe disease subjects with ventilatory insufficiency. Safety was assessed by measurement … [Read more]
Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy
Glucocorticoid treatment is recommended as a standard of care in Duchenne muscular dystrophy; however, few studies have assessed the long-term benefits of this treatment. In this prospective cohort study, the authors examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in male patients aged 2-28 years with Duchenne … [Read more]
Natural history of infantile-onset SMA
Clinical trials in patients with infantile-onset spinal muscular atrophy (SMA) require an understanding of disease progression and identification of meaningful biomarkers to hasten therapeutic development and predict outcomes. This longitudinal, multi-center, prospective natural history study enrolled 26 SMA infants, and 27 control infants less than six months of age. Recruitment occurred at 14 centers over … [Read more]
IL-8 and SDF1A as biomarkers for Inclusion Body Myositis disease progression
Inclusion body myositis is a late onset inflammatory myopathy lacking reliable serum biomarkers for diagnosis and for disease progression. To identify diagnostic and predictive biomarkers, cytokine profiling is used to assess the potential of cytokines to discriminate between cases and controls and to assess whether treatment with methotrexate can influence biomarkers associated with disease … [Read more]
Expanding the genetic, clinical and neuropathological features of Brown-Vialetto-Van Laere syndrome
Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency, neuropathology and downstream consequences of riboflavin transporter mutations … [Read more]
Effective induction therapy for anti-SRP associated myositis in childhood: A small case series and review of the literature
Anti-Signal Recognition Particle (SRP) associated myopathy is a clinically and histopathologically distinct subgroup of Juvenile Idiopathic Inflammatory Myositis (JIIM), which is under-recognised in children and fails to respond to conventional first line therapies. Thus far, the paediatric literature has demonstrated a picture consistent with the adult population, however only a handful of cases have … [Read more]
