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  • Publication : 27 11 2018
  • Catégorie :La recherche médicale et génétique

Clinical Review Report: Nusinersen (Spinraza): (Biogen Canada Inc.): Indication: Treatment of patients with 5q SMA    

Abstract
Spinal muscular atrophy (SMA) is a severe neuromuscular disease and is the leading genetic cause of infant death. It is characterized by the degeneration of alpha motor neurons in the anterior horn of the spinal cord, leading to progressive muscle weakness. Neurological studies indicate that the disease causes a rapid and irreversible degeneration of motor neurons. The rate of motor neuron degeneration has been reported to plateau with time. The most common form of SMA, 5q SMA, makes up more than 95% of all cases and is an autosomal recessive disorder caused by homozygous deletion or deletion and mutation of the alleles of the survival motor neuron 1 (SMN1) gene. While deletion or mutation of the SMN1 gene results in survival motor neuron (SMN) protein deficiency (which is essential for the development of motor neurons), the survival motor neuron 2 (SMN2) gene produces a relatively small amount of functional SMN protein and SMN2 copy number modulates the severity of the disease. SMA is a rare disease and estimates of its incidence and prevalence vary between studies. The incidence of SMA is often cited as being approximately 10 in 100,000 live births. Incidence and prevalence estimates in Canada are not well described in the literature. However, the manufacturer of nusinersen provided Canadian figures of an annualized estimate of new cases of SMA in Canada at 37.2 new cases per year. Four clinical subtypes of SMA are described. SMA type I makes up about 60% of SMA diagnoses where patients show symptoms before 6 months of age, never achieve the motor milestone of sitting unsupported, and generally do not survive past two years of age due to respiratory failure. Patients with SMA type II achieve the milestone of sitting unsupported, but never walk independently. Symptoms generally appear between 6 to 18 months after birth. Most patients will survive past the age of 25, with life expectancy improved by aggressive supportive care. SMA type III makes up about 10% to 20% of SMA cases and presents between 18 months of age and early adulthood. These patients are able to walk independently at some point in their life and typically have a normal life expectancy. SMA type IV constitutes a very small proportion of SMA cases, has an adult onset, and is the mildest form of the disease. Although muscle weakness is present, these patients retain the ability to walk, have a normal life expectancy, and do not suffer from respiratory or nutritional issues.

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