nusinersen and Respiratory-Insufficiency

Spinal muscular atrophy [SMA] is the most common genetic cause of childhood mortality, primarily from the most severe form SMA type 1. It is a severe, progressive motor neurone disease, affecting the lower brainstem nuclei and the spinal cord. There is a graded level of severity with SMA children from a practical viewpoint described as "Non-sitters", "Sitters" and less commonly, "Ambulant" correlating with SMA Type 0/Type 1, Type 2 and Type 3 respectively. Children with SMA Type 0 have a severe neonatal form whilst those with SMA Type 1 develop hypoventilation, pulmonary aspiration, recurrent lower respiratory tract infections, dysphagia and failure to thrive before usually succumbing to respiratory failure and death before the age of 2 years. The recent introduction of the antisense oligonucleotide nusinersen into clinical practice in certain countries, following limited trials of less than two years duration, has altered the treatment landscape and improved the outlook considerably for SMN1 related SMA. Approximately 70% of infants appear to have a clinically significant response to nusinersen with improved motor function. It appears the earlier the treatment is initiated the better the response. There are other rarer genetic forms of SMA that are not treated with nusinersen. Clinical expectations will change although it is unclear as yet what the extent of response will mean in terms of screening initiatives [e.g., newborn screening], "preventative strategies" to maintain respiratory wellbeing, timing of introduction of respiratory supports, and prolonged life expectancy for the subcategory of children with treated SMA type 1. This article provides a review of the strategies available for supporting children with respiratory complications of SMA, with a particular emphasis on SMA Type 1.

Topics: Early Medical Intervention; Humans; Hypoventilation; Life Expectancy; Oligonucleotides; Phenotype; Physical Therapy Modalities; Pneumonia; Respiration, Artificial; Respiratory Aspiration; Respiratory Insufficiency; Respiratory Therapy; Spinal Muscular Atrophies of Childhood

To analyze the efficacy and safety of nusinersen in patients with spinal muscular atrophy (SMA) type I with chronic respiratory failure.. We retrospectively reviewed seven patients diagnosed with SMA type I and chronic respiratory failure who were on permanent ventilation and treated with nusinersen at Gangnam Severance Hospital between January 2018 and July 2023. Patient demographics and clinical characteristics were recorded, and treatment progress was evaluated according to Hammersmith Infant Neurological Examination (HINE-2) and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores.. Patients initially developed hypotonia at a mean age of 3.7 months. Mean age at start of nusinersen was 7.3 years; the mean duration of follow-up after starting nusinersen was 46.2 months. At 6-, 18-, 38-, 58-, and 74-month follow-up, the mean changes in CHOP-INTEND scores were 1.0, 2.9, 1.8, 1.5, and 1.5, respectively, and the proportions of patients who showed disease amelioration were 28.6%, 71.4%, 75.0%, 100%, and 100%, respectively.. Nusinersen is safe and effective in patients with SMA type I, even those with chronic respiratory failure and those on permanent ventilation. No significant adverse effects of nusinersen were observed.

Topics: Child; Humans; Infant; Muscular Atrophy, Spinal; Republic of Korea; Respiratory Insufficiency; Retrospective Studies; Spinal Muscular Atrophies of Childhood

To examine the effect of intrathecal application of nusinersen on the respiratory function in terms of vital capacity in pediatric patients with spinal muscular atrophy (SMA). SMA is characterized by on-going muscular atrophy and weakness that lead to respiratory insufficiency. In recent years therapy with nusinersen has been shown to improve motor function in patients with SMA.. We retrospectively analyzed data from 12 pediatric patients (aged 4-12 years) with SMA II or III (7 walkers, 5 sitters) treated with nusinersen. We examined forced vital capacity (FVC) at baseline (i.e., before treatment) and 180 and 300 days after initiation of treatment.. No significant difference in the ranks of FVC of patients with SMA at baseline and day 300 was found and, thus, stable FVCs are implied (n = 6; Z = - 0.105, p. Nusinersen therapy alone may not improve lung function of pediatric patients with SMA type II or III.

Topics: Child; Child, Preschool; Cohort Studies; Female; Humans; Injections, Spinal; Male; Muscular Atrophy, Spinal; Oligonucleotides; Respiratory Insufficiency; Retrospective Studies; Vital Capacity

Topics: Humans; Infant; Male; Oligonucleotides; Respiratory Function Tests; Respiratory Insufficiency; Spinal Muscular Atrophies of Childhood

Topics: Drug Costs; Genetic Therapy; Humans; Muscular Atrophy, Spinal; Noninvasive Ventilation; Oligonucleotides; Prognosis; Respiratory Insufficiency; Survival of Motor Neuron 2 Protein