What is Spinal Muscular Atrophy?

Spinal Muscular Atrophy, commonly known as SMA, is a genetic disorder that affects the motor neurons in the spinal cord. These neurons are essential for muscle movement. SMA causes motor neurons to break down, leading to muscle weakness and paralysis.  

What causes SMA?

SMA is an inherited disorder that occurs in around one in 6000-10000 live births and most commonly manifests during childhood. Alongside Cystic Fibrosis and Tay-Sachs disease, SMA is one of the top three genetic causes of child mortality in North America. 

SMA is caused by a mutation in the survival motor neuron 1 (SMN1) gene. This gene is responsible for producing a protein that protects motor neurons from damage. When the SMN1 gene is mutated, it leads to a shortage of this crucial protein, causing motor neurons to die. One in every 50 people carry the SMA gene. If both parents have the gene, there is a one in four chance their child will develop the disease. 

What are the types of SMA?

Currently SMA is classified into five different types based on the age of onset and physical milestones reached. This approach to classification is undergoing changes, however, due to developing understanding of the condition and its treatments.

Type 0: Type 0 SMA

Type 0 SMA is a rare form of SMA that starts in utero. The fetus might move less during later stages of pregnancy. At birth children display muscle weakness and difficulty in breathing. 

Type 1: Werdnig-Hoffmann Disease

Type 1 SMA, also known as Werdnig-Hoffmann disease, accounts for 80% of SMA cases. It typically becomes evident before six months of age. Babies with Type 1 SMA show signs of muscle weakness, poor muscle tone, and difficulties with breathing and swallowing. These infants often cannot lift their heads or sit without support. Without treatment, children with Type 1 SMA often do not survive past the age of two.

SMA Type 2:

Symptoms of SMA Type 2 usually appear between 6 and 18 months of age. Children with Type 2 SMA can typically sit without support but have muscle weakness in the legs. Breathing issues develop over time. Most people with type 2 SMA live to adolescence or adulthood.

Type 3: Kugelberg-Welander Disease

Type 3 SMA, also known as Kugelberg-Welander disease, becomes evident after the age of 18 months. Individuals with Type 3 SMA can walk as children, but they may have difficulty with activities that require strength and endurance, like running or climbing stairs. As they age, some may lose the ability to walk and require a wheelchair. 

Type 4: Adult-Onset SMA

Type 4 SMA typically appears in adulthood, usually after the age of 20. Symptoms progress more slowly than in other types. Individuals with Type 4 SMA may experience mild to moderate muscle weakness, usually affecting the legs and hips. They often maintain the ability to walk throughout their lives and have an average life expectancy.

What are the Symptoms of SMA?

The symptoms of SMA vary depending on the type and progression of the disease. Common symptoms include:

• Muscle Weakness: This is the most prominent symptom of SMA. It can affect the legs, arms, chest, and face, leading to difficulties with movement and physical activities.
• Poor Muscle Tone: Individuals with SMA may have weak or loose limbs due to low muscle tone.
• Breathing Problems: Weakness of the respiratory muscles can cause difficulties in breathing and coughing which increases the risk of lung infections.
• Feeding and Swallowing Difficulties: Muscle weakness can make it hard to chew and swallow food, potentially leading to nutritional issues, choking, and weight loss.
• Unmet Motor Milestones: Infants and children with SMA might not reach motor milestones such as sitting, crawling, and walking.

How is SMA Treated? 

While there is no cure for SMA, recent advancements have significantly improved the outlook for individuals with this condition. 

Medications

Several medications have been developed to treat SMA. Screening newborns is important, because treatment is more successful if patients are treated before they begin to show symptoms. For some people with SMA, medications approved for use in both youths and adults may not be covered by insurance providers, limiting access to treatment. Without insurance, these medications can cost hundreds of thousands of dollars per year in US dollars.

Approved treatments for SMA include:

• Nusinersen (Spinraza): This drug is a gene therapy that boosts production of the SMN protein. Spinraza can partially compensate for the defective SMN1 gene and slow progression of the disease. It is administered via spinal injections and has been approved for use in all ages.
• Onasemnogene abeparvovec (Zolgensma): This gene therapy delivers a working copy of the SMN1 gene to motor neurons through a single intravenous infusion. It is designed for use in children under two years old.
• Risdiplam (Evrysdi): This oral medication works similarly to Spinraza to increase SMN protein production. It can be taken at home and is approved for patients of all ages.

Supportive Therapies

Supportive therapies can help manage SMA symptoms and improve quality of life. These may include:

• Physical Therapy: Helps maintain muscle strength and flexibility, preventing contractures (muscle stiffness and atrophy) and improving mobility.
• Occupational Therapy: Assists with daily activities and adapting the home environment to meet the individual’s needs.
• Respiratory Care: Includes techniques and devices to support breathing, such as cough assist machines, BiPAP machines, and regular monitoring of lung function.
• Nutritional Support: Ensures proper nutrition, which may involve dietary modifications and, in some cases, feeding tubes.
• Assistive Devices: Various assistive devices can help individuals with SMA maintain independence and improve their quality of life. These include wheelchairs, braces, and standing frames. Adaptive technology, such as communication devices and specialized computer equipment, can also make it easier for people with SMA to communicate and engage with the world.

Living with SMA

Living with SMA can be complex, but with the right support and resources, individuals with SMA are able to lead fulfilling lives. Advocates are fighting for better access to treatment and supportive care.

Thank you to Karli Drew for her generosity with her time and helpful edits. 

References

Day, J. W., Howell, K., Place, A., Long, K., Rossello, J., Kertesz, N., & Nomikos, G. (2022). Advances and limitations for the treatment of spinal muscular atrophy. BMC pediatrics, 22(1), 632. https://doi.org/10.1186/s12887-022-03671-x

Dubowitz V. Very severe spinal muscular atrophy (SMA type 0): an expanding clinical phenotype. Eur J Paediatr Neurol. 1999;3(2):49-51. doi:10.1053/ejpn.1999.0181

Emmady, P. D., & Bodle, J. (2023). Werdnig-Hoffmann Disease. In StatPearls. StatPearls Publishing. Accessed June 17, 2024 from https://pubmed.ncbi.nlm.nih.gov/32644359/#:~:text=Werdnig%2DHoffmann%20disease%2C%20also%20known,and%20lack%20of%20motor%20development.

Erdos, J., & Wild, C. (2022). Mid- and long-term (at least 12 months) follow-up of patients with spinal muscular atrophy (SMA) treated with nusinersen, onasemnogene abeparvovec, risdiplam or combination therapies: A systematic review of real-world study data. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 39, 1–10. https://doi.org/10.1016/j.ejpn.2022.04.006

National Institute of Neurological Disorders and Stroke (2023). Spinal Muscle Atrophy. Accessed June 17, 2024 from https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy

Nishio, H., Niba, E. T. E., Saito, T., Okamoto, K., Takeshima, Y., & Awano, H. (2023). Spinal Muscular Atrophy: The Past, Present, and Future of Diagnosis and Treatment. International journal of molecular sciences, 24(15), 11939. https://doi.org/10.3390/ijms241511939