Spinal Muscular Atrophy (SMA) is a genetic disorder that affects the motor neurons in the spinal cord, leading to muscle weakness and atrophy. It is one of the most common genetic causes of infant mortality, with an estimated incidence of 1 in 10,000 live births.
The history of SMA dates back to the late 19th century, when French neurologist Aran first described the disease in 1850. He identified a group of children who presented with progressive muscle weakness and atrophy, but the cause of the condition remained unknown for many years.
In the early 20th century, researchers began to recognize the hereditary nature of SMA. In 1900, German neurologist Werdnig described a form of infantile spinal muscular atrophy, now known as SMA type 1 or Werdnig-Hoffmann disease. He observed that the disease was present from birth and led to severe muscle weakness and respiratory difficulties.
Advancements in genetics and molecular biology in the latter half of the 20th century played a crucial role in understanding the underlying cause of SMA. In the 1990s, researchers discovered that SMA is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which is responsible for producing a protein essential for the survival of motor neurons.
Further research revealed that SMA is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated SMN1 gene (one from each parent) to develop the disease. Individuals with only one copy of the mutated gene are carriers and do not typically show symptoms.
In recent years, significant progress has been made in the treatment of SMA. In 2016, the U.S. Food and Drug Administration (FDA) approved nusinersen, marketed as Spinraza, as the first-ever treatment for SMA. Nusinersen is an antisense oligonucleotide that targets the SMN2 gene, a closely related gene that produces a less functional form of the SMN protein. By increasing the production of functional SMN protein, nusinersen helps improve motor function in individuals with SMA.
Another breakthrough in SMA treatment came in 2019, when the FDA approved onasemnogene abeparvovec, marketed as Zolgensma, as a gene therapy for SMA. Zolgensma is a one-time intravenous infusion that delivers a functional copy of the SMN1 gene to motor neurons, addressing the underlying genetic cause of SMA.
These advancements in treatment have provided hope for individuals with SMA and their families. Ongoing research continues to explore new therapeutic approaches, including gene editing techniques and other innovative strategies, with the aim of further improving the outcomes and quality of life for individuals affected by this devastating disease.