Clinical Background

Spinal muscular atrophy (SMA) is a rare, genetic, neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. It has an incidence rate of about 1 in 6000 to 1 in 10,000 live births. Based on age of onset and motor function achieved, SMA is classified into types 1 through 4.1 

Type 1: This is the most common and severe type and is sometimes referred to as Werdnig-Hoffmann disease. Type 1 accounts for about 50% of all diagnoses, affecting infants with an onset of clinical signs before 6 months of age. They never gain the ability to sit unsupported and generally do not survive beyond 2 years of age. All children with SMA type 1 display a combination of severe hypotonia and weakness, but the disease spares facial muscles. The weakness is typically symmetrical, and lower limbs generally weaker than upper limbs. Deep tendon reflexes are absent or diminished but sensitivity is preserved.1

Type 2: Affects children between 7 and 18 months of age. These children can sit unsupported and some may stand but they cannot walk. Deep tendon reflexes are absent and fine tremors of upper extremities are common. Joint contractures and abnormal spinal curvature is common and can occur in the first years of life. For some, swallowing may be difficult and weak jaw muscles can affect the ability to chew.1

Type 3: Has a moderate disease course and is sometimes referred to as a Kugelberg-Welander disease. Children with type 3 can reach all major motor milestones and walk independently. During infancy, they may develop proximal muscular weakness. Some children may need a wheelchair but most can stand and walk unaided. Over time, walking and climbing stairs may become difficult and, later, in life a wheelchair may be needed for many of these individuals. Individuals who lose the ability to walk often develop scoliosis and other medical problems related to poor mobility, such obesity and osteoporosis.1

Type 4 is the least severe and affects people over 18 years of age. Patients with this type can walk, well into adulthood, and don’t develop respiratory or nutritional problems.1


Amifampridine Phosphate in SMA

Catalyst is initiating a clinical development plan exploring the use of amifampridine phosphate, a neuronal potassium channel blocker, for the treatment of SMA.

Learn more about Amifampridine Phosphate.


  1. D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis. 2011;6:71.

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