Can a Full Life Be Possible for a Child with SMA? Gene Correction Technologies in Medicine

Spinal muscular atrophy (SMA) is a rare genetic condition that affects motor neurons in the spinal cord. As a result, patients experience progressive muscle weakness and atrophy, which impacts their ability to walk, move, and, in severe cases, breathe and swallow. In this article, we provide essential information for individuals seeking knowledge about the disease, its diagnosis, and available treatments.

SMA Is Caused by a Random Gene Mutation

SMA occurs due to mutations in the SMN1 gene, which is responsible for producing the critical survival motor neuron (SMN) protein. This protein enables motor neurons to transmit signals from the brain to the muscles. When the body lacks SMN protein, motor neurons begin to die, leading to muscle weakness and gradual atrophy. Identifying mutations in the SMN1 gene is a key step in diagnosing the condition.

Analysis of another gene, SMN2, plays a supportive role. Often referred to as a “pseudogene,” SMN2 also produces the SMN protein, but in significantly smaller amounts. The number of SMN2 gene copies a patient has affects disease severity: fewer copies (1-2) are associated with severe forms of SMA (Type 1), while more copies (4 or more) lead to a milder disease progression.

Mutations in the SMN1 gene that cause SMA are inherited in an autosomal recessive manner. This means a child must inherit two defective copies of the gene — one from each parent — for the disease to develop. Parents themselves are asymptomatic carriers of the mutation and are often unaware of their status until a child is born with SMA.

Carrier status can only be identified through genetic testing, which is recommended during family planning. This test helps assess the risk of having a child with SMA and, if necessary, consider preventive measures, such as assisted reproductive technologies (ART).

According to the latest in vitro fertilization (IVF) protocols, preimplantation genetic testing for embryos includes SMA as part of standard screening panels in specialized clinics. This allows for the prevention of the disease even before implantation.

Types of SMA

SMA is classified into several clinical types based on the age of onset and severity of symptoms:

• Type 1 SMA (Werdnig-Hoffmann disease): The most severe form, appearing within the first six months of life. Patients experience severe hypotonia, lack of motor activity, and difficulty breathing. Without treatment, life expectancy rarely exceeds two years.
• Type 2 SMA: This type manifests between six and 18 months of age. These children can sit but cannot walk. Without treatment, significant muscle weakness and scoliosis develop over time.
• Type 3 SMA (Kugelberg-Welander disease): A milder form with symptoms that may appear between 18 months and adolescence. Patients can walk independently, although this ability may be lost in later years.
• Type 4 SMA: A rare adult-onset form characterized by mild muscle weakness, primarily in the proximal limbs.

Correcting the Defective Gene Is Possible

In some countries, prenatal testing for SMA is available, but it is not yet standard in newborn screening programs. This often leads to late diagnosis, only after symptoms appear. In newborns, SMA may present as low muscle tone (hypotonia), lack of reflexes, feeding difficulties, and breathing problems. If these symptoms are observed, immediate medical consultation is essential.

Online consultations with a geneticist and neurologist enable a prompt evaluation of symptoms and guidance on testing and treatment options. SMA diagnosis requires genetic testing, and even with a confirmed diagnosis, seeking a second opinion from a specialized clinic is advisable to ensure accuracy and rule out potential errors. This is particularly crucial for initiating gene therapy, which is most effective during the first three years of life.

Gene therapy is a revolutionary approach that offers an innovative solution to the root cause of genetic disorders. It works at the DNA level, providing cells with a “correct” version of the defective gene. For SMA treatment, vector systems — modified viruses — are used to deliver the genetic material to cells without causing infections.

The core mechanism of gene therapy involves:

1. Delivering a functional copy of the SMN1 gene using an adeno-associated virus (AAV) as a safe vector, which inserts the gene into cells without causing disease.
2. Once inside the cells, the gene begins producing the required SMN protein.
3. Restoring SMN protein levels prevents further motor neuron death and slows disease progression.

According to the World Health Organization (WHO), the prevalence of SMA is approximately 1 in 10,000 live births. Without treatment, severe forms are often fatal within the first years of life.

Two Approaches to SMA Therapy

For treating Types 1 and 2 SMA, two main therapeutic mechanisms are used: gene therapy and antisense oligonucleotide (ASO) therapy. Gene Therapy (e.g., Zolgensma): Restores function by adding the missing gene. ASO Therapy (e.g., Spinraza): Enhances the function of another gene (SMN2), compensating for the lack of SMN protein.

Zolgensma

Zolgensma is the only FDA-approved gene therapy for SMA. It targets the root cause of the disease — SMN1 gene mutations. The drug delivers a functional copy of the gene using a modified AAV9 virus. Following a single administration, the gene integrates into cells, enabling the continuous production of SMN protein essential for motor neuron health.

The treatment is most effective in children under three years old, as their nervous systems remain highly plastic, and the number of irreversibly damaged neurons is minimal. Clinical studies show that 95% of children treated with Zolgensma at early stages of SMA achieve motor milestones such as sitting or walking independently.

Spinraza

Spinraza (nusinersen) increases SMN protein levels in SMA patients by improving the splicing process of the SMN2 gene and enhancing its functionality. This slows disease progression, improves motor function, and stabilizes the patient’s condition.

Spinraza is suitable for patients of all ages, including those with advanced stages of SMA. However, treatment requires regular intrathecal injections every four months throughout the patient’s life. While the administration procedure can be complex, long-term data confirm its effectiveness in improving motor skills and quality of life.

Comparison of SMA Treatments: Zolgensma vs. Spinraza

Characteristic	Zolgensma	Spinraza
Type of Therapy	Gene Therapy	Antisense Therapy
Frequency of Dosing	Single	Regular (every 4 months)
Administration Method	Intravenous infusion (1 hour)	Lumbar puncture (spinal injection)
Mechanism of Action	Replaces SMN1 gene	Enhances SMN2 function
Efficacy	High when used early (<3 years)	High at all ages and stages
Cost	~$2.1 million (one-time)	$125,000 per injection ($500,000/year)
Availability	Available in the US, Europe, Japan, Canada, Australia, Saudi Arabia, South Korea, and most European countries	Available worldwide, including Russia and the CIS