From the Guidelines
Yes, spinal muscular atrophy (SMA) is a motor neuron disease. It is a genetic disorder characterized by the degeneration of motor neurons in the spinal cord and brainstem, which leads to progressive muscle weakness and atrophy. SMA is caused by mutations in the SMN1 gene, which produces a protein essential for the survival of motor neurons. When these motor neurons deteriorate, they cannot send signals to muscles, resulting in muscle weakness and wasting. There are several types of SMA (types 0-4), classified based on age of onset and severity of symptoms.
Key Points
- SMA is a genetic disorder that affects motor neurons in the spinal cord and brainstem
- It is characterized by progressive muscle weakness and atrophy
- SMA is caused by mutations in the SMN1 gene
- Treatment options include FDA-approved medications such as nusinersen (Spinraza), onasemnogene abeparvovec-xioi (Zolgensma), and risdiplam (Evrysdi)
- Early diagnosis and treatment are crucial for better outcomes, as these therapies are most effective when started before significant motor neuron loss has occurred, as noted in the evaluation of motor neuron diseases 1.
Diagnosis and Treatment
The diagnosis of SMA is typically made through a combination of clinical evaluation, genetic testing, and imaging studies. Treatment options have expanded in recent years and include FDA-approved medications that work by increasing the production of functional SMN protein.
- MRI head without IV contrast is usually appropriate for the initial imaging of patients with suspected motor neuron disease, including SMA 1
- MRI spine without IV contrast may be appropriate for certain patients with suspected motor neuron disease, particularly to exclude structural, infectious, or neoplastic etiologies of the spine that can mimic motor neuron disease 1
From the FDA Drug Label
EVRYSDI is a survival of motor neuron 2 (SMN2) splicing modifier indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients. The FDA drug label does not answer the question.
From the Research
Definition and Classification of Spinal Muscular Atrophy
- Spinal muscular atrophy (SMA) is typically characterized as a motor neuron disease 2
- SMA is caused by low levels of the survival motor neuron (SMN) protein, which is ubiquitously expressed, but the disease selectively affects motor neurons, leading to progressive muscle weakness 3
Characteristics of Spinal Muscular Atrophy
- SMA is a multisystem disease with dysfunction in skeletal muscle, heart, kidney, liver, pancreas, spleen, bone, connective tissues, and immune systems 2
- The disease selectively affects motor neurons, but certain motor units appear more clinically resistant to SMA 3
- SMA type 1 is a severe form of the disease, associated with progressive muscle weakness, ventilatory failure, and reduced survival 4
Treatment and Management of Spinal Muscular Atrophy
- Nusinersen, an antisense oligonucleotide drug, has been shown to improve motor function and respiratory outcomes in patients with SMA 5, 6, 4
- Risdiplam is another FDA-approved treatment for SMA, and transitioning from nusinersen to risdiplam has been shown to be safe and efficacious 6
- The effectiveness of treatment depends on various factors, including disease duration and the presence of invasive ventilation 4