Spinal muscular atrophy or SMA in children represents a group of rare genetic (inherited) neuromuscular disorder, causing muscles throughout the body to become weak and shrink (atrophy). SMA involves the loss of a specific type of nerve cells in spinal cord due to a faulty or missing gene. Without these nerve cells, muscles do not receive the nerve signals that allow them to move. Besides impaired physical movement and breathing ability, SMA drastically affects child’s growth and development. Due to medical advancements in bioengineering and genomic medicines, Gene therapy has emerged as a novel approach to treat SMA in children aiming at replacing the defective genes, enabling an improved motor function while offering an improved patient’s quality of life.
Get to know “spinal muscular atrophy or SMA”
Spinal muscular atrophy or SMA is an autosomal recessive disease. Given that, it mostly means that both parents must carry the genetic mutation for a child to develop the condition. SMA involves the loss of a specific type of nerve cells in spinal cord called lower motor neurons, or anterior horn cells. The loss of these nerve cells is induced by a faulty or missing gene, known as “survival of motor neuron 1 or SMN 1” on the 5th chromosome. As these nerve cells control certain muscle movement throughout the body, without these motor neurons, muscles do not receive the nerve signals that allow them to move. It results in impaired physical movement, limited breathing and swallowing ability as well as child’s growth and development. The approximate incidence rate of SMA is 1 in 6,000 to 10,000 live births each year and the carrier rate is at 1: 40 – 1:60. Children aged younger than 2 years old presenting with serious signs and symptoms of SMA are at greater risk of death. An effective treatment for SMA is highly recommended in children before manifestation arises or at age of 6 weeks, enabling a higher chance of successful treatment outcome.
What are alarming signs and symptoms of SMA?
Signs and symptoms of SMA in children are classified based on the age of onset, as well as the severity and life expectancy. There are 4 types, including:
- Spinal muscular atrophy type 0 (SMA type 0)
This is a rare type that affects infants at birth, causing severe muscle weakness and respiratory failure. Death usually happens at birth or within the first month of life. - Spinal muscular atrophy type 1 (SMA type 1)
Considered the most common and severe form of SMA, SMA type 1 is typically found in babies aged 2-6 months. Signs and symptoms often involve muscle atrophy and weakness, leading to limited movement, such as difficulty sitting up, crawling or walking, trouble breathing, feeding and swallowing as well as lack of reflexes. Children with SMA type 1 usually require respiratory support through ventilators. Most patients die by the age of 2 years without ventilator support. - Spinal muscular atrophy type 2 (SMA type 2)
Symptoms of SMA type 2 or intermediate SMA often appear between 6- 18 months of life. Symptoms include worsening muscle weakness, which tends to affect their legs more than their arms. Children with type 2 SMA may be able to sit up but they cannot walk. Other manifestation includes difficulty swallowing and breathing, tremors, or uncontrollable shaking in the fingers. - Spinal muscular atrophy type 3 (SMA type 3)
Considered a milder form, SMA type 3 appears at age of 18 months – 2 years of life. Symptoms include lower limb muscle weakness, leading to difficulty walking. Patients with SMA type 3 do not tend to develop breathing issues, and it typically does not affect life expectancy.
How to diagnose SMA in children?
- Thorough medical history assessment
- Physical examination, electromyography (EMG) and nerve conduction study – a test that shows how muscles are receiving signals from the nerves and muscle enzyme
- Genetic testing – A blood test to look for mutations of SMN gene on the 5th chromosome.
What are treatment options for SMA in children?
There is not a cure for SMA. Treatment for SMA conducted by pediatricians mainly seeks to manage symptoms and prevent complications, based on age and disease severity. Main management therapies are:
- Disease-modifying therapy: These medications stimulate the production of SMN protein. Medications are administered through an injection into the spinal fluid (intrathecal) by a lumbar puncture (spinal tap).
- Symptomatic treatment: Such as ventilation assistance, physical and occupational therapy, rehabilitation and support devices.
- Gene therapy: One-time gene therapy treatment replaces the defective or missing gene of SMN1, which is responsible for making the survival motor neuron (SMN) protein. Gene therapy has been approved for treating SMA by US FDA in 2019 and by Thai FDA in 2023.
What is gene therapy?
Gene therapy has emerged as a groundbreaking approach, leveraging genetic material to cure or prevent diseases by replacing defective gene – SMN1 during the earliest stage of the disease. Gene therapy for SMA primarily uses a modified, non-replicating adeno-associated virus vector to deliver a functional SMN1 gene to lower motor neurons or anterior horn cells, addressing the root cause of SMA. A one-time intravenous (IV) infusion of a medication will be administered by well-trained and licensed pediatricians in certified hospitals.
Who are good candidates for gene therapy?
To achieve the best possible treatment outcome, gene therapy is recommended in newborn diagnosed with SMA from after birth until 24 months of age. Treatment efficacy is significantly reduced if medication is administered in children aged over 2 years old.
What are benefits obtained from gene therapy?
- For children presenting without signs or symptoms – Gene therapy is likely to improve their movement, allowing them to be able to sit and walk.
- For children presenting with signs and symptoms – In symptomatic children, gene therapy can result in improved muscle strength, showing significant motor improvement.
- Newborn or baby with SMA type 1 – Early treatment of gene therapy given to children with SMA type 1 can result significantly in improving motor function, increasing survival rates and reducing the need for permanent ventilation and nutritional support.
Patient instruction prior to gene therapy
- Liver function test
- Kidney function test
- Immunity and specific antibody test
- Complete blood count (CBC)
- Cardiac function test and baseline Troponin-I levels (cardiac enzyme)
Possible side effects of gene therapy
- An elevated liver enzyme
- Low platelet count (thrombocytopenia)
- An increased Troponon-I level
How can we prevent SMA in children?
Since SMA is a genetic condition, it cannot be directly prevented once inherited, as it stems from a faulty SMN1 gene. In terms of inheritance risk, if both parents are carriers, there is a 25% (1 in 4) chance in each pregnancy of having a child with SMA and a 50% chance of having a child who is also a carrier. Prevention strategies focus on genetic carrier screening for prospective parents, prenatal testing during pregnancy and using IVF with preimplantation genetic testing to ensure embryos do not carry the disease.
A one-time gene therapy treatment for spinal muscular atrophy (SMA) is particularly effective if started early, even before symptoms of SMA appear. Compared to other approaches, this ground-breaking treatment offers superior advantages, with improved motor function while promoting survival rates and reducing ventilation assistance. Nevertheless, gene therapy should be initiated and administered in the hospital adhering to international standards and supervised by highly expert pediatricians and multidisciplinary team specialized in the management of patients with SMA.
How can we screen for SMA?
To screen for SMA, tests involve premarital (before conceiving), prenatal (during pregnancy) and newborn screening.
- Premarital screening for SMA carriers – To screen for asymptomatic carriers of SMA among couples (both male and female), allowing for genetic counseling and informed reproductive choices to prevent the birth of children with the disease. Screening uses blood samples and genetic testing (qRT-PCR technique) to detect the abnormality of SMN1 gene (SMN1 deletion / mutation). By identifying at-risk couples before pregnancy, it significantly reduces morbidity and mortality related to SMA.
- Preimplantation Genetic Testing during IVF/ ICSI treatment – For couples undergoing fertility treatment using IVF or ICSI, to screen for SMA in the embryos the process involves removing embryo cells (biopsy) at the blastocyst stage and conducting preimplantation genetic testing to detect mutation of SMN1 gene. This helps ensuring only unaffected embryos are transferred for implantation. It allows couples who are carriers of SMA to conceive a child without the disease.
- Prenatal screening and diagnosis – To identify the risk of fetuses having SMA in pregnant women, maternal blood is used, preferably in the first trimester. If SMA is suspected, it further requires confirmed prenatal SMA diagnosis using Chorionic Villus Sampling (CVS) or amniocentesis. If a pregnancy is confirmed to have affected status with SMA, it allows for early intervention and treatment planning to improve potential outcomes.
- Newborn screening – Newborn SMA screening aims to identify SMA in infants shortly after birth, typically within the first few days of life, in order to initiate life-altering, pre-symptomatic treatment. Collected samples are dried blood spots via heel prick to genetically detect the abnormality of SMN1 gene. This newborn screening aims to prevent irreversible motor neuron loss, significantly improving long-term health outcomes and survival rates.
Gene therapy for treating SMA at Child’s Health Center, Bangkok Hospital
Our pediatrician and multidisciplinary teams at Child’s Health Center, Bangkok Hospital are highly experienced in managing genetic neuromuscular disorders in children of all age, including SMA. Our center is fully-equipped with cutting-edge technology and facilities in pediatric care, ensuring appropriate treatment and care best suited to each child and family.
Pediatricians specialized in treating SMA at Child’s Health Center, Bangkok Hospital
- Dr. Thianchai Bunnalai (American Board of Pediatrics and Pediatric Critical Care Medicine)
- Dr. Suchawadee Horsuwan (Pediatric Neurology)
