Types, Symptoms, and Treatment of Spinal Muscular Atrophy (SMA)

Spinal Muscular Atrophy (SMA) Details: Classifications, Signs, and Therapies

Spinal muscular atrophy (SMA), a group of genetic disorders that cause muscle weakness and atrophy, affects one in every 8,000-10,000 people worldwide. Fortunately, two FDA-approved drugs, Spinraza and Zolgensma, are now available to help manage the condition.

For infants diagnosed with SMA at birth, both Spinraza (nusinersen) and Zolgensma (onasemnogene abeparvovec) have demonstrated significant benefits, especially when treatment starts early, ideally pre-symptomatically.

Spinraza, an antisense oligonucleotide (ASO) therapy, is administered repeatedly to enhance survival motor neuron (SMN) protein production. Data shows that early Spinraza treatment leads to improved motor milestones, with about 50% of patients achieving new motor skills such as sitting and walking within a year, even in some cases where prior treatment with Zolgensma was inadequate. Neurofilament light chain (NfL), a biomarker for neurodegeneration, drops rapidly and remains low under Spinraza treatment, indicating slowed disease progression and validating its effectiveness for long-term neurological stability.

Zolgensma, a one-time gene replacement therapy, delivers a functional copy of the SMN1 gene via an AAV9 viral vector. It is specifically approved for infants under 2 years of age and functions by halting the progression of SMA at the genetic level. Clinical experience and case studies show that Zolgensma can significantly improve motor function and survival if given early, ideally before significant motor neuron loss occurs at birth or soon after. While Zolgensma is a single-dose therapy, ongoing studies are investigating long-term safety and durability of its response, with early indications of sustained benefit.

Infants with SMA lose about half their motor neurons by birth, so early intervention is critical to preserving motor function. The expansion of newborn screening programs globally allows earlier diagnosis and treatment initiation, which is crucial since infants with SMA lose motor neurons quickly after birth.

While both treatments offer substantial long-term benefits, each has its advantages. Zolgensma offers a one-time gene replacement therapy that halts disease progression early, while Spinraza requires ongoing dosing but effectively slows neurodegeneration and promotes motor milestone gains. The combination or sequential use of therapies is being explored, and new therapies like apitegromab are emerging as add-ons to gene or ASO therapies to further improve motor function.

Assistive devices and therapy can also improve a person's life expectancy and quality of life with SMA, including ventilators, powered wheelchairs, modified computer access, physical therapy, and water therapy. As these treatments are new, long-term outcomes are not yet known, but the future looks promising for those affected by SMA.

For infants diagnosed with SMA at birth, Zolgensma (onasemnogene abeparvovec), a one-time gene replacement therapy, can significantly improve motor function and survival.
Spinraza (nusinersen), an antisense oligonucleotide (ASO) therapy, is administered repeatedly to enhance survival motor neuron (SMN) protein production, leading to improved motor milestones in about 50% of patients within a year.
Neurological-disorders like Spinal muscular atrophy (SMA) affect one in every 8,000-10,000 people worldwide, causing muscle weakness and atrophy.
Medical-conditions such as SMA often require therapies-and-treatments like Spinraza and Zolgensma to help manage their progression, with each having its advantages: Zolgensma offers a one-time gene replacement therapy while Spinraza requires ongoing dosing.
Therapies like physical therapy, water therapy, and assistive devices like ventilators and powered wheelchairs can improve life expectancy and quality of life for people living with SMA.
Science and healthcare advancements have led to the development of FDA-approved drugs for SMA, including Spinraza and Zolgensma, providing hope for those diagnosed with this genetic disorder.