Comprehensive Guide to Spinal Muscular Atrophy (SMA)

Understanding Spinal Muscular Atrophy (SMA)

Spinal muscular atrophy (SMA) is a genetic disorder that affects the nerves responsible for controlling voluntary muscles, as detailed by the Muscular Dystrophy Association (MDA). This condition can cause severe physical disabilities, including paralysis and life-threatening respiratory issues.

SMA targets specialized nerve cells known as motor neurons located in the spinal cord and brainstem. When these neurons degenerate, the muscles they control weaken progressively, often starting with the legs and trunk before affecting the arms and breathing muscles. This decline can lead to significant mobility challenges and respiratory complications.

Tragically, SMA is a leading cause of infant mortality. However, advances in medical research and treatment over recent years have significantly improved the prognosis for individuals living with SMA.

Causes and Types of SMA

SMA is caused by mutations in the SMN1 gene, leading to a deficiency in the survival motor neuron (SMN) protein essential for motor neuron health. The severity of the disease correlates with the number of copies of a related gene, SMN2, that a person has; more copies generally mean milder symptoms.

Most SMA cases are inherited in an autosomal recessive pattern, requiring individuals to inherit two defective copies of the SMN1 gene—one from each parent. Carriers typically show no symptoms but can pass the gene to their children.

SMA is classified into several types based on age of onset and severity: Type 0 (prenatal), Type I (most severe, beginning in infancy), Type II (chronic, starting in infancy), Type III (chronic, beginning in childhood), Type IV (mild, starting in adulthood), and SMA with respiratory distress (SMARD1).

Importance of Early Detection and Treatment

In the U.S., newborn screening for SMA is widespread, allowing early diagnosis before symptoms appear. Early detection is crucial since it enables timely treatment—maximizing motor development and survival rates. Since 2016, three groundbreaking therapies have transformed SMA treatment:

• Gene therapy (Zolgensma): Single infusion delivering a functional copy of the SMN1 gene.
• Antisense therapy (Spinraza): Spinal injections that modify gene splicing to increase protein production.
• SMN2 splicing modifier (Evrysdi): An oral medication enhancing SMN protein synthesis.

These treatments have saved lives and improved the quality of life, with many children reaching developmental milestones previously thought unattainable.

Future Directions in SMA Research

Research continues to push the boundaries in SMA care. Current efforts focus on enhancing drug delivery, accessibility, and efficacy, such as studies investigating higher dosages and early intervention in presymptomatic individuals. Regenerative approaches, including stem cell therapies and neuroprotective agents, aim to repair or replace damaged neurons.

Combination therapies, pairing gene treatment with drugs targeting muscle or inflammation, are under investigation to achieve comprehensive disease management. Additionally, prenatal screening and in utero interventions hold promise for preventing or delaying neuron degeneration.

Supporting Progress through Advocacy

Organizations like MDA have been instrumental in advancing SMA research and care. Their support has enabled significant breakthroughs, including the development of Spinraza. Continued advocacy and investment are vital for sustaining progress and improving outcomes for all individuals affected by SMA.

Source: https://medicalxpress.com/news/2025-08-spinal-muscular-atrophy.html