Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.
SMA type 2
Spinal muscular atrophy (SMA) type 2 is an intermediate form of SMA, the symptoms of which usually appear between ages 6 and 12 months.1
SMA Type 2 Causes
SMA type 2 is caused by mutations in a gene called SMN1.2 The SMN1 gene resides on chromosome 5 and encodes the SMN protein.3 The SMN protein is essential for the survival of motor neurons. Mutations in the SMN1 gene prevent the production of functional SMN protein from this gene.
SMA is classified into different types, depending on the severity of the symptoms and their age of onset. SMA type 2 is an intermediate form of the disease.
What determines the severity of the disease in large part is the number of copies of the SMN2 gene,4 which also codes for SMN protein. However, most (85% to 90%) of the SMN protein that cells make from SMN2 is shorter than normal and quickly degraded. This is due to alternative splicing where the exon 7 is missing from the mature SMN2 mRNA.
The number of SMN2 gene copies a person has can vary between 2 and 8. The more copies a person has, the more SMN protein their body can make. So the symptoms of SMA tend to be milder and appear later in people who have more copies of the SMN2 gene. Those with SMA type 2 usually have 3 copies of the SMN2 gene.4
SMA Type 2 Symptoms
Symptoms of SMA type 2 usually appear when a baby is between ages 6 and 12 months. They include muscle weakness, floppiness, and finger tremors.5 Muscle weakness in SMA tends to affect the legs more than the arms. Additionally, the proximal muscles are more severely affected than the distal muscles.6
The rate of progression of the disease can vary greatly from patient to patient. However, individuals affected by SMA type 2 can’t stand or walk without assistance.2
Because muscles that control breathing are affected, patients often have breathing difficulty and, because they cannot cough effectively, they experience frequent respiratory infections. These infections can become severe and life-threatening.
Weakness in the muscles that are necessary for chewing and swallowing also means that patients have difficulty feeding. Finally, because the muscles supporting the spinal column are weakened, scoliosis may develop. Hip dislocations are also common.6
SMA type 2 does not affect bladder or bowel control or sexual or intellectual development.7 Depending on the severity of the symptoms, life expectancy can range from early childhood to adulthood.2
SMA Type 2 Diagnosis
If there is a family history of SMA or if the disease is suspected based on the physical examination, a genetic test looking for mutations in the SMN1 gene should be conducted.6
If this test shows abnormalities in the SMN1 gene, other family members of the patients may also be offered a genetic test to assess their carrier status.
SMA Type 2 Treatment Options
The US Food and Drug Administration (FDA) has approved 3 disease-modifying treatments for SMA type 2. Two of these, nusinersen (SpinrazaⓇ) and risdiplam (EvrysdiⓇ) increase the amount of SMN protein that cells can make from the SMN2 gene.
Nusinersen does this by “masking” the signal in the SMN2 gene that causes the SMN protein to be shorter than normal. The FDA approved nusinersen in December 2016 for the treatment of patients with SMA types 1, 2, and 3 of any age.10 It is an intrathecal injection with a recommended dosage of 12 mg (5 mL) per administration. Treatment starts with 4 loading doses (the first 3 administered at 14-day intervals and the fourth administered 30 days after the third dose) and continues with maintenance doses administered every 4 months.11
Risdiplam also works by increasing the amount of SMN protein that cells make from SMN2. It is a small molecule treatment that corrects the splicing of the SMN2 gene. The FDA approved it in August 2020 for patients aged 2 years and older with all types of SMA.12 It is a single daily liquid treatment that patients take orally for the rest of their lives.
Onasemnogene abeparvovec-xioi (ZolgensmaⓇ) uses a different approach to modify the course of SMA. As a gene therapy, it aims to deliver a healthy copy of the SMN1 gene to the body to increase the amount of SMN protein. It does so using adeno-associated virus 9 (AAV9), a modified virus that is not harmful. It was approved by the FDA in May 2019 to treat patients with all types of SMA up to age 2 years.13 It is a signal treatment that is infused into the bloodstream.
Patients with SMA type 2 may also need other forms of treatment to increase their quality of life and reduce their symptoms. These include breathing and feeding support, mobility aids, physiotherapy and occupational therapy, and in some cases, surgery to correct scoliosis.6
Reviewed by Michael Sapko, MD on 7/1/2021
- Spinal muscular atrophy type 2. Genetic and Rare Disease Information Center. Accessed May 26, 2021.
- Spinal muscular atrophy (SMA). Cleveland Clinic. Accessed May 26, 2021.
- SMN1 gene. Medline Plus. Accessed May 26, 2021.
- Butchbach MER. Copy number variations in the survival motor neuron genes: Implications for spinal muscular atrophy and other neurodegenerative diseases. Front. Mol. Biosci. 2016;3:7.doi: 10.3389/fmolb.2016.00007
- Tsirikos AI, Baker ADL. Spinal muscular atrophy: classification, aetiology, and treatment of spinal deformity in children and adolescents. Curr. Orthop. 2006;20(6);430-45. doi: 10.1016/j.cuor.2006.09.006
- Type 2. SMA Europe. Accessed May 26, 2021.
- Montes J, Gordon AM, Pandya S, et al. Clinical outcome measures in spinal muscular atrophy. J Child Neurol. 2009;24(8);968-78. doi: 10.1177/0883073809332702
- Carrier. National Human Genome Research Institute. Accessed May 26, 2021.
- Carrier testing for spinal muscular atrophy FAQ. University of California San Francisco Health. Accessed May 26 ,2021.
- FDA approves first drug for spinal muscular atrophy. News release. US Food and Drug Administration. December 23, 2016.
- Spinraza prescribing information. US Food and Drug Administration. Accessed May 26, 2021.
- FDA approves oral treatment for spinal muscular atrophy. News release. US Food and Drug Administration. August 7, 2020.
- FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality. News release. US Food and Drug Administration. May 24, 2019.