Clinician's Guide to Spinal Muscular Atrophy

Jump to:
Medical advisors icon

Meet our

Medical advisors

Edward Smith, M.D.

Edward Smith, MD

Melissa Wright, MD, PhD

Case Scenario: How to Treat a Patient with Established SMA

Written by Margaret Anne Rockwood | Last updated July 7th, 2026
✅ Medically reviewed by Edward Smith, MD

 

The diagnosis of spinal muscular atrophy (SMA) once largely determined a patient’s prognosis. Today, disease-modifying therapies (DMTs) target the fundamental deficiency of survival motor neuron (SMN) protein and have dramatically altered the natural history of SMA.

Once SMA type is established, the clinician’s role shifts from diagnosis to treatment selection, functional preservation, complication prevention, and long-term monitoring.

Presymptomatic treatment remains the goal, as motor neuron loss begins before clinical weakness becomes apparent. Studies consistently show that infants treated before symptoms develop achieve better outcomes than those treated after weakness appears. Even when treatment has not been initiated early, current evidence supports consideration of DMT for most patients with SMA, including adolescents and adults.

Preserving the Existing Baseline

Currently available DMTs are not able to restore lost motor neurons, so treatment goals are based on disease stage and the amount of function that remains.

For instance, in an infant identified through newborn screening, the goal may be the achievement of normal developmental milestones. For an adolescent with SMA type 2, preserving upper-extremity function and respiratory independence may be paramount. For a middle-aged adult with longstanding SMA type 3, maintaining ambulation or preventing further decline may represent a meaningful therapeutic success.

Accordingly, initial assessment should document:

  • ambulatory status
  • upper-limb function
  • bulbar function
  • respiratory capacity
  • endurance and fatigue
  • activities of daily living

These baseline measurements provide an objective framework for future monitoring and help establish realistic treatment goals. Importantly, clinicians should recognize that stabilization itself may represent a successful outcome in a progressive neurodegenerative disease.

How to Select the Most Appropriate Therapy

There is no universally accepted algorithm that identifies a single best therapy for every patient. Instead, treatment selection is individualized and depends on disease stage, remaining motor neuron reserve, route of administration, treatment burden, safety considerations, and patient preferences.

Age and Disease Stage

Age matters less because of chronology itself, and moreso in terms of remaining motor neuron reserve. A presymptomatic newborn may still have most motor neurons intact. In that setting, the goal may be normal motor development. By contrast, an adult with longstanding SMA has already experienced years or decades of motor neuron loss. Even if SMN protein production is improved, treatment cannot restore neurons that have already died.

As disease progresses, therapeutic goals shift from developmental gains to preservation of existing function and slowing future decline.

DMT Options

Gene Therapies

Onasemnogene abeparvovec-xioi (Zolgensam) and onasemnogene abeparvovec-brve (Itvisma) are one-time gene-replacement therapies that deliver a functional copy of SMN1 using an AAV9 viral vector.

Patients receiving either drug, both manufactured by Novartis Gene Therapies, must undergo liver function testing before treatment and careful monitoring afterward because hepatic inflammation may occur and corticosteroid therapy is routinely required. Patients must also undergo screening for preexisting antibodies against the AAV9 viral vector, as high antibody levels may render a patient ineligible or reduce treatment effectiveness.

For established patients ≥2 years of age, onasemnogene abeparvovec-brve is the only available option. Eligibility requirements include age, a confirmed SMN1 mutation, screening for anti-AAV9 antibodies, baseline liver-function and safety evaluation, and the ability to undergo corticosteroid therapy and post-treatment monitoring; patients previously treated with Zolgensma are not candidates for Itvisma.

ASO Therapy

Nusinersen (Spinraza Biogen) is an antisense oligonucleotide (ASO) administered intrathecally every four months. Factors influencing patient selection should include:

  • ability to undergo repeated lumbar punctures
  • severe scoliosis or spinal fusion surgery
  • need for ongoing maintenance dosing
  • tolerance of image-guided procedures or sedation when necessary

A patient with extensive spinal hardware may still receive nusinersen, but treatment may become technically challenging.

RNA Splicer

Risdiplam (Evrysdi, Genentech) is an oral SMN2 splicing modifier taken daily. Factors influencing patient selection should include:

  • ability to take daily medication consistently
  • swallowing function or feeding-tube access
  • potential adverse effects and monitoring requirements
  • preference for home administration

Because it is administered orally, risdiplam is often attractive for adolescents and adults, particularly those with scoliosis, prior spinal fusion, or limited access to specialty centers.

Whereas gene therapy eligibility is influenced by factors such as age, body weight, liver status, and AAV9 antibodies, selection between nusinersen and risdiplam in older patients is often driven more by practical considerations, including spinal anatomy, procedural burden, treatment adherence, and patient preference.

Many adults with longstanding SMA are candidates for either nusinersen or risdiplam, and decision-making is often surprisingly practical. Patients who wish to avoid repeated lumbar punctures may favor risdiplam, while others may prefer nusinersen because of familiarity with long-term experience or concerns about daily medication adherence.

Longitudinal Monitoring & Supportive Care

Physicians and patients can both benefit from systematic monitoring tailored to age and functional status.

Commonly used outcome measures include:

Additional monitoring may include pulmonary function testing, swallowing assessments, nutritional evaluation, scoliosis surveillance, and patient-reported outcome measures.

As treated patients live longer and achieve higher levels of function, ongoing monitoring becomes increasingly important for identifying emerging complications and guiding long-term management.

The introduction of DMTs does not eliminate the need for supportive care. Comprehensive multidisciplinary management remains essential. Patients should continue to undergo regular assessment for scoliosis, contractures, restrictive lung disease, swallowing dysfunction, nutritional compromise, osteoporosis, and chronic pain.

Physical and occupational therapy also remain key components of care, helping patients maximize function and maintain flexibility. Respiratory support continues to play a critical role for many patients, particularly those with more severe phenotypes. Common interventions include cough-assist devices, airway-clearance techniques, noninvasive ventilation when indicated, and management of sleep-disordered breathing.

Pulmonologists, rehabilitation specialists, nutritionists, orthopedic surgeons, speech/language pathologists, physical and occupational therapists, and neuromuscular neurologists should all have a role in the patient’s long-term care plan.

How to Treat Adults with Longstanding Disease

Perhaps the most important change in modern practice involves adults who spent much of their lives living with SMA prior to the availability of DMTs.

Adults with SMA type 2, type 3, and type 4 were historically managed with supportive care alone and often told that little could be done to alter the course of their disease. Today, that view is changing.

As noted, DMTs cannot restore motor neurons that have already been lost nor can they reverse decades of established weakness, contractures, or skeletal deformities. Nevertheless, accumulating evidence suggests that many adults can experience stabilization of motor function, preservation of upper-limb function, improvements in endurance, or meaningful improvements in quality of life with these new therapies.

For individuals who have experienced years of gradual decline, the psychological impact of slowing or stopping further deterioration may itself represent an important clinical success.

Decision-making on the use of DMTs and supportive care in these patients should emphasize individualized goals. Some may prioritize maintaining independence in daily activities, while others may focus on preserving respiratory function or delaying loss of ambulation.

Sources