Spinal Muscular Atrophy Treatment in Delhi, India

Spinal Muscular Atrophy (SMA) is a rare genetic disease that affects the nerve cells in the spinal cord and brainstem, called motor neurons. These neurons are responsible for sending signals from the brain to the muscles, allowing us to move. In SMA, these motor neurons are damaged or lost, leading to progressive muscle weakness and atrophy (shrinking). This can affect various muscle groups, impacting movement, breathing, and other vital functions.

There are several types of SMA, classified based on the age of onset and severity of symptoms.

The classification system typically includes the following types:

SMA Type 1

Also known as Werdnig-Hoffmann disease or severe infantile SMA, this is the most severe form of SMA, with onset typically occurring within the first few months of life. Babies with Type 1 SMA have profound muscle weakness, difficulty swallowing and breathing, and generally have a significantly shortened life expectancy.

SMA Type 2

This form typically presents between 6 and 18 months of age. Children with Type 2 SMA can usually sit unsupported but may have difficulty walking and may require assistance for mobility. While life expectancy may be better than Type 1, it can still be significantly impacted.

SMA Type 3

Also known as Kugelberg-Welander disease or mild SMA, this form typically manifests after 18 months of age, often during childhood or adolescence. Individuals with Type 3 SMA may be able to walk independently but may experience progressive muscle weakness over time. Life expectancy can vary widely depending on the severity of symptoms.

SMA Type 4

SMA Type 4 or Adult SMA is the mildest and rarest form of SMA, with onset typically occurring in adulthood. Symptoms are usually milder compared to other types of SMA, and individuals may experience slowly progressive muscle weakness and atrophy. Life expectancy is usually normal, and individuals may have a relatively normal lifespan.

These classifications provide a general framework for understanding the different presentations of SMA, but it's important to note that there can be significant variability in symptoms and progression within each type.

Spinal Muscular Atrophy (SMA) is primarily caused by a genetic mutation in the Survival Motor Neuron 1 (SMN1) gene, located on chromosome 5. This gene is responsible for producing a

protein called Survival Motor Neuron (SMN) protein, which is crucial for the health and function of motor neurons.

The most common cause of SMA is the deletion or mutation of the SMN1 gene. Individuals typically inherit two copies of the SMN1 gene, one from each parent. In SMA, one copy of the SMN1 gene is typically mutated or missing altogether, leading to a deficiency of the SMN protein.

Without adequate levels of SMN protein, motor neurons gradually degenerate, leading to muscle weakness, atrophy, and eventually, loss of motor function. The severity of SMA symptoms depends on the extent of SMN protein deficiency, with individuals having fewer functional copies of the SMN1 gene generally experiencing more severe symptoms.

While the SMN1 gene is the primary genetic factor involved in SMA, other genetic and environmental factors may also influence disease severity and progression. Ongoing research into these factors aims to provide further insights into the causes of SMA and potential avenues for treatment and management.

The severity and onset of symptoms can vary widely depending on the type of SMA and individual factors. Common symptoms of SMA may include:

• Muscle Weakness: Weakness in the muscles, particularly those closest to the centre of the body, such as the shoulders, hips, and thighs, is a hallmark symptom of SMA. This weakness may be mild initially but tends to worsen over time.
• Poor Muscle Tone: Individuals with SMA may have reduced muscle tone, leading to floppiness or difficulty maintaining posture.
• Difficulty with Motor Skills: Children with SMA may experience delays in motor milestones such as sitting, crawling, and walking. In severe cases, they may never achieve these milestones without intervention.
• Respiratory Problems: Weakness in the muscles involved in breathing can lead to respiratory difficulties, including shortness of breath, shallow breathing, and an increased risk of respiratory infections.
• Swallowing Difficulties: Weakness in the muscles involved in swallowing may cause feeding difficulties, choking, or aspiration.
• Joint Contractures: Prolonged muscle weakness can lead to joint contractures, where the joints become stiff and difficult to move.
• Progressive Disability: Without intervention, muscle weakness and atrophy in SMA typically worsen over time, leading to progressive disability and loss of motor function.

• Genetic Testing: The primary method for diagnosing SMA is through genetic testing, which involves analysing DNA to identify mutations or deletions in the Survival Motor Neuron 1 (SMN1) gene. This testing can confirm the presence of SMA and determine the type and severity of the condition.
• Clinical Evaluation: Healthcare providers may perform a thorough clinical evaluation to assess muscle strength, tone, and motor function. They may also look for characteristic signs and symptoms of SMA, such as muscle weakness, poor reflexes, and motor delays.
• Electromyography (EMG): EMG is a test that measures the electrical activity of muscles and can help assess the health and function of motor neurons. Abnormal EMG findings, such as reduced muscle activity, may support the diagnosis of SMA.
• Nerve Conduction Studies: Nerve conduction studies can evaluate the speed and strength of nerve signals travelling to muscles. Abnormal results may indicate dysfunction of motor neurons associated with SMA.
• Muscle Biopsy: In some cases, a muscle biopsy may be performed to examine muscle tissue under a microscope. Muscle biopsies can reveal characteristic changes associated with SMA, such as muscle fibre atrophy and motor neuron loss.

Early diagnosis of SMA is crucial for implementing timely interventions and initiating appropriate treatments to help manage the condition and improve outcomes for affected individuals.

There is currently no cure for SMA, but there are treatments that can help manage the symptoms and improve quality of life. The main types of treatment for SMA include:

Disease-modifying Therapies

These medications help to increase the production of the survival motor neuron (SMN) protein, which is important for the health of motor neurons. There are two FDA-approved disease-modifying therapies for SMA:

• Nusinersen (Spinraza): This medication is injected into the spinal canal and is approved for use in all types of SMA.
• Risdiplam (Evrysdi): This medication is taken orally and is approved for use in adults and children ages 2 months and older.

Gene Therapy

This treatment involves delivering a healthy copy of the SMN1 gene to the body. Zolgensma (onasemnogene abeparvovec) is a gene therapy that is approved for use in children under the age of 2 with SMA.

Supportive Therapies

These therapies help to manage the symptoms of SMA and improve quality of life. They may include:

• Physical Therapy: This can help to improve muscle strength and function, prevent contractures, and maintain range of motion.
• Occupational Therapy: This can help people with SMA develop the skills they need to perform daily activities.
• Respiratory Therapy: This can help people with SMA manage breathing problems.
• Nutritional Support: This is important for people with SMA to maintain a healthy weight and get the nutrients they need.
• Assistive Devices: These can help people with SMA stay mobile and independent, such as wheelchairs, braces, and walkers.

It is important to note that the best treatment for SMA will vary depending on the individual's type and severity of the disease.

SMA, unfortunately, does not come without its complications. These can vary depending on the type and severity of the disease, but some common ones include:

• Muscle Weakness and Wasting: This is the core symptom of SMA, leading to difficulty with movement, swallowing, and breathing. This can limit mobility, independence, and overall quality of life.
• Respiratory Problems: Weak muscles in the chest can make breathing difficult, especially during sleep. This can lead to respiratory infections and, in severe cases, respiratory failure.
• Bone Problems: Reduced mobility and muscle weakness can increase the risk of fractures and scoliosis (curvature of the spine).
• Nutritional Deficiencies: Difficulty swallowing and chewing can make it challenging to get enough nutrients, leading to malnutrition and dehydration.
• Joint Contractures: Tightness and shortening of muscles and tendons can limit joint movement and cause pain.
• Speech Difficulties: Weak muscles in the mouth and throat can make it difficult to speak clearly.
• Psychological Issues: Living with a chronic illness like SMA can lead to anxiety, depression, and social isolation.

Currently, there is no way to completely prevent SMA. However, there are efforts aimed at reducing the risk of having a child with SMA:

• Carrier Screening: This involves testing potential parents to see if they carry the gene mutation that causes SMA. If both parents are carriers, there's a 25% chance their child will have SMA.
• Prenatal Testing: If both parents are carriers, prenatal testing can be done during pregnancy to check if the foetus has SMA.
• Gene Therapy: Although still in early stages, gene therapy holds promise for preventing SMA by delivering a healthy copy of the SMN1 gene to the foetus before birth.
• Preimplantation Genetic Diagnosis (PGD): This advanced technique involves selecting embryos free of the SMA gene mutation for implantation during IVF. However, it raises ethical concerns and is not widely available.

It's important to remember that these are just potential approaches, and further research is needed to develop effective and accessible prevention strategies for SMA.

Q1. How common is Spinal Muscular Atrophy?

Spinal Muscular Atrophy (SMA) is a relatively rare genetic disorder, but it is one of the most common inherited causes of infant mortality. The prevalence of SMA varies among different populations and ethnic groups, but it is estimated to affect approximately 1 in 10,000 live births worldwide.

Q2. What's the difference between SMA and Muscular Dystrophy?

Both affect muscles, but they target different parts:

• SMA: Attacks motor neurons, the nerve cells controlling muscle movement.
• Muscular Dystrophy: Primarily affects the muscles themselves.

Symptoms and progression also differ significantly between the two.

Q3. Can adults develop SMA?

Yes, although most cases are diagnosed in children (infantile-onset SMA), adult-onset forms (types 3 & 4) exist. These tend to be milder but can still cause progressive weakness and movement difficulties.

Q4. Can SMA be diagnosed during pregnancy?

Yes, prenatal testing options like amniocentesis and chorionic villus sampling can detect SMA if both parents are carriers or there's a family history.

Q5. What's the life expectancy for someone with SMA?

It depends heavily on the type and severity of the disease. Severe forms diagnosed early may have shorter lifespans, while milder forms allow individuals to live well into adulthood. Advances in treatment are improving the outlook for many with SMA.

Q6. How does SMA progress over time?

SMA generally progresses gradually, with symptoms like muscle weakness worsening over time. However, the rate of progression varies significantly between individuals. Some may experience periods of stability or improvement with treatment.

Q7. How does SMA impact mobility?

Muscle weakness and function are affected, leading to difficulties with movement like walking, climbing stairs, and using arms. The degree of impact depends on the type and severity of SMA. Assistive devices can help maintain mobility.

Q8. Can SMA affect heart health?

While not directly affecting the heart muscle, SMA's impact on breathing and reduced mobility can indirectly affect heart health. Regular screenings and monitoring are crucial.

Q9. Can SMA cause scoliosis?

Yes, weak back muscles can lead to scoliosis, a curvature of the spine. Early diagnosis and treatment can help manage and prevent severe curvature.

Q10. Are there special dietary needs for individuals with SMA?

Yes, increased energy expenditure and swallowing difficulties may require higher nutritional needs. A balanced diet with sufficient protein, calories, and essential nutrients is crucial. Consulting a registered dietitian is recommended.

Q11. What are the challenges of living with SMA?

Physical limitations, fatigue, pain, and emotional difficulties are common challenges. However, access to support services, therapy, and assistive technology can significantly improve quality of life.

Q12. What role does physical therapy play in managing SMA?

Physical therapy is crucial for maintaining muscle strength, range of motion, and preventing contractures. It can also improve balance, coordination, and overall functional ability.

Q13. Can SMA affect cognitive function?

No, SMA primarily affects motor neurons, not the brain, so it typically doesn't impact cognitive function. However, fatigue and pain management may indirectly affect cognitive abilities.

Q14. What's the outlook/prognosis for people with SMA?

The outlook is improving thanks to advancements in treatment and research. Early diagnosis and proper care significantly enhance quality of life and life expectancy. While individual experiences vary, ongoing research offers hope for further progress.

Reviewed by Dr. Puneet Agarwal, Principal Director - Stroke and Dementia, Neurosciences, Neurology on 12 Mar 2024.