How does spinal muscular atrophy affect the body

How does spinal muscular atrophy affect the body?

What's Spinal Muscular Atrophy (SMA)?

The inherited neuromuscular condition Spinal Muscular Atrophy (SMA) causes muscle weakening and atrophy. The mutated SMN1 gene produces the motor neuron survival protein. Without this protein, spinal cord motor neurons degenerate, inhibiting the brain-muscle connection.

Types of SMA

Age of onset and severity classify SMA into five types:

Type 0: Rare and severe, it causes respiratory collapse in newborns before birth.
Type 1 (Werdnig-Hoffman disease): The most frequent type forms before 6 months of life and causes significant muscle weakness and breathing problems.
Type 2 (Dubowitz disease): Symptoms appear between 6 and 18 months, affecting sitting but not walking.
Type 3 (Kugelberg-Welander disease): Develops after 18 months, inhibits walking but does not shorten life.
Type 4 SMA is characterized by the mildest onset of muscular weakening in adults.

SMA emotionally impacts individuals and families.

SMA symptoms

SMA impairs muscle strength and movement, with symptoms depending on type and degree. Some common signs:

All-around symptoms

Weak arms, legs, and trunk muscles.
Depending on the type of SMA, individuals may experience difficulties with sitting, standing, or walking.
Twitching muscles.
Severe breathing and swallowing issues.
Joint and scoliosis issues.

Symptoms by Type

Type 0: Weak muscular tone, joint issues, and respiratory issues at birth.
Type 1: Floppy limbs, swallowing issues, respiratory weakness.
Type 2 SMA is characterized by weaker legs compared to arms and difficulty sitting up.
Type 3: Trouble walking, climbing stairs, or standing.
Type 4: Adult muscular weakness impacting mobility.

An injection for SMA

For infants under 2, we use Zolgensma, a gene therapy, to treat Spinal Muscular Atrophy (SMA). It provides a functioning SMN1 gene to save motor neurons and increase muscle function. However, Zolgensma is among the most costly drugs worldwide, costing ₹17–18 crore per dose.

How Zolgensma Works

It replaces the SMN1 gene that causes SMA.
Each dose requires a single IV infusion.
It slows down the progression of illness and enhances the mobility of muscles.

Availability in India

In India, doctors can import Zolgensma with government approval and a doctor's recommendation.
Some families crowdfunded injections to get therapy.

SMA type 1

SMA Type 1, also known as Werdnig-Hoffman disease, is the most prevalent and severe variant. In the first six months of life, it causes fast muscular weakening and motor function loss.

For infants with SMA Type 1, symptoms may include:

Poor muscle tone (hypotonia) hinders mobility.
The condition results in poor head control and the inability to sit or roll over.
Issues with swallowing and nutrition lead to stunted growth.
Frequent breathing issues requiring respiratory support.
Weak respiratory muscles cause a bell-shaped chest.

Causes

A mutation in the SMN1 gene causes spinal cord motor neuron degeneration in SMA Type 1.
Muscle weakening progresses due to brain-muscle communication issues.

Treatment and Prognosis,

Early gene therapy (Zolgensma), Spinraza (Nusinersen), or Risdiplam can increase life expectancy and quality of life. There is no cure. Life expectancy without therapy is usually less than two years; however, modern medicines have greatly increased survival.

SMA type 2

SMA Type 2, commonly known as Dubowitz disease, is an intermediate form of SMA that occurs between 6 and 18 months of age. Though milder than Type 1, it causes gradual muscle weakness in the legs and arms.
Spinal Muscular Atrophy (SMA) can deeply affect individuals and their families. Living with SMA can impair mental health, relationships, and well-being beyond physical restrictions.

The emotional impact of loss and grief can lead to chronic sadness, which is often caused by the loss of mobility and freedom.

Mental Health Issues:

When daily tasks and social interactions are challenging, anxiety, depression, and loneliness are widespread.
Some individuals embrace SMA as an integral part of their identity, while others grapple with the emotional burden of adaptation.

Social Challenges:

Dependence on caregivers and accessibility difficulties can isolate people, making employment, relationships, and hobbies tougher.

Family Emotional Impact

Parents' Grief and Fear: SMA infant diagnosis generally causes shock, pain, and grief for parents.
Family caregivers may feel exhausted juggling medical duties and their well-being.
Financial and Lifestyle Changes: Treatment and assistance gadgets are expensive, which can strain families.
Building Support Networks: Support groups, therapy, and community engagement help SMA families cope emotionally.

Despite these challenges, therapy, social support, and lifestyle changes can help people and families cope.

SMA therapy

Spinal Muscular Atrophy (SMA) has no cure, although some treatments can halt disease development and improve quality of life. Main therapeutic options:

Disease-Changing Drugs

Some SMA treatments target the genetic cause:

Spinraza (Nusinersen): An FDA-approved medication that increases SMN protein production to save motor neurons.
Zolgensma: A gene therapy for infants under 2 years old that replaces the defective SMN1 gene.
Risdiplam (Evrysdi) is an oral medication that boosts SMN protein levels and is approved for use in individuals aged 2 months and older.

Supportive Treatments

SMA decreases muscular strength and mobility, necessitating supportive treatment.
Physical therapy prevents joint stiffness.
For breathing problems, ventilation or airway clearance may be necessary.
Nutritional support, such as the use of feeding tubes, is provided for patients who struggle with swallowing
Surgery for scoliosis or braces may be necessary.

Researchers are investigating new therapeutics, such as stem cell treatments and small-molecule medications, to enhance SMA care.

SMA Type 2 kids may:

Leg weakness makes standing or walking difficult.
Poor muscle tone causes floppy limbs.
Loss of muscle reflexes is observed.
Weak spinal muscles cause scoliosis.
Lung infections worsen with breathing problems.
Despite their ability to sit independently, many youngsters experience delayed motor development.

Management & Treatment

Although there is no cure, early intervention can enhance mobility and lifespan.

The injectable Nusinersen (Spinraza) increases SMN protein synthesis.
Risdiplam (Evrysdi): Oral SMN protein booster.
Zolgensma: Gene therapy for younger neonates.
Physical treatment and mobility aids.
Care for breathing, including ventilation.
SMA Type 2 patients can live into maturity with supportive care and effective therapy.

SMA type 3

SMA Type 3, commonly known as Kugelberg-Welander disease, is a milder form of SMA that emerges after 18 months and before adulthood. Type 3 SMA patients live long lives but may lose their ability to walk.

Symptoms

Patients often experience frequent falls and struggle with climbing stairs.
The patient may experience weakness in their thighs, which could extend to their arms and shoulders.
The development of motor skills is later.
Issues with waddling and walking arise.
Reflexes may be weak or nonexistent.
Finger tremors.
In certain circumstances, scoliosis and breathing issues follow walking loss.

Causes

Mutations in the SMN1 gene induce motor neuron degeneration in SMA Type 3. These people have three to four copies of the SMN2 gene, which produces protein.

Management & Treatment

Although there is no cure, various therapies can halt disease progression :

The injectable Nusinersen (Spinraza) increases SMN protein synthesis.
Risdiplam (Evrysdi): Oral SMN protein booster.
PT prevents joint stiffness and maintains mobility.
One can opt for braces or undergo surgery for scoliosis.

SMA Type 4: The mildest and rarest form appears in adulthood, usually after 21. This type progresses slowly and does not impair life expectancy.

Symptoms

The symptoms include weakness in the muscles of the legs and hips.
The patient experiences hand tremors and twitches.
Less severe breathing issues than other SMA variants.
Poor walking, especially waddling.
Muscle compensation causes calf enlargement.

Causes

SMA Type 4 causes motor neuron degeneration due to SMN1 gene mutations. These people have three to five copies of the SMN2 gene, which produces protein.

Diagnostics and Treatment

Genetic testing shows SMA Type 4.
Electromyography (EMG) and nerve conduction studies evaluate muscle function.
FDA-approved Nusinersen (Spinraza) increases SMN protein synthesis.
Physical therapy maintains strength and mobility.

SMA lifespan

The kind and severity of Spinal Muscular Atrophy (SMA) affect life expectancy. General breakdown:

SMA life expectancy Type 0 is the most severe and rare kind, affecting newborns before birth. Life expectancy is below months.
Type 1 (Werdnig-Hoffmann disease): Symptoms develop before 6 months. Life expectancy is usually under 2 years without therapy; however, modern medicines have greatly increased survival.
Symptoms of Type 2 (Dubowitz illness) appear between 6 and 18 months of age.
Many people live into their 20s and 40s, with respiratory issues being a prominent worry.
Type 3 (Kugelberg-Welander) happens after 18 months. Most people have normal lives, but they may lose mobility.
Type 4: Adulthood's mildest kind. Although gradual muscle weakness may develop, it does not affect life expectancy.

Treatment Effect

Gene therapy (Zolgensma), Spinraza (Nusinersen), and Risdiplam have greatly improved SMA Types 0, 1, and 2 survival rates. Early intervention improves life expectancy and quality.

Pregnancy SMA symptoms

Although there is limited evidence, Spinal Muscular Atrophy (SMA) may complicate pregnancy. Important considerations:

Possible Signs and Effects

Increased muscle weakness: Many pregnant SMA patients report severe leg and respiratory muscle tiredness.

Some need breathing help due to weaker diaphragm muscles.
Studies reveal a higher risk of preterm labor and miscarriage.
SMA patients have increased C-sections due to muscular weakness.
Challenges of postpartum recovery: Some develop chronic weakness.

SMA Pregnancy Management

Monitoring: Neurologists and obstetricians can assist in managing symptoms with regular visits.
PT: Maintains mobility and reduces muscle strain.
Doctors may prescribe a breathing aid.
Genetic counseling assesses SMA risk to the infant.

Spinal muscular atrophy

SMA results from a mutation in the SMN1 gene, which is responsible for producing the survival motor neuron (SMN) protein. Motor neurons, which move muscles, need this protein to operate properly. Without adequate SMN protein, motor neurons degenerate, causing muscular weakness and atrophy.

A genetic cause

An MA mutation or deletion in the SMN1 gene on chromosome causes most cases of SMA (Types 1-4).
The severity of SMA depends on the number of copies of the SMN2 gene, which produces a limited quantity of functional SMN protein.
Mutations in other genes, like UBE1, generate rare forms of SMA, such as X-linked SMA.

Development of SMA

A kid must inherit two defective copies of the SMN1 gene (one from each parent) to develop SMA.
Parents with one defective SMN1 gene are carriers but do not get SMA.
Genetic testing can detect carrier status and children's SMA risk.

Conclusion

Gene therapy and specialized drugs now give SMA patients lifesaving treatments that reduce symptoms and extend life expectancy. Supportive treatments such as physical therapy, respiratory aid, and lifestyle changes improve well-being.

Raising awareness, enhancing treatment access, and building a strong support system for SMA patients and families are crucial.

Vaalga Endrum