There are several approved treatments for spinal muscular atrophy (SMA). Each individual or family must make treatment decisions based on your needs, goals, and values in consultation and discussion with your healthcare provider.
Due to a mutation in the survival motor neuron gene 1 (SMN1), individuals with SMA do not produce survival motor neuron (SMN) protein at high enough levels. Without this protein, the motor neuron cells shrink and eventually die. This causes debilitating and potentially fatal muscle weakness.
One way of treating SMA is to increase the amount of survival motor neuron protein in the body. This is often called an “SMN-based” or “SMN-enhancing” approach.
All individuals with SMA have at least one, and often multiple, copies of a second gene called survival motor neuron gene 2 (SMN2) or the “SMA back-up gene.” SMN2 also produces SMN protein, but at a significantly lower quantity compared to the SMN1 gene.
Many SMN-enhancing treatments target the SMN2 gene, causing it to make more useable SMN protein. Other SMN-enhancing approaches work to replace the function of or repair the mutated SMN1 gene.
Increasing the amount of SMN protein in the body is not the only way to treat SMA. The loss of SMN protein also impacts other systems, pathways, and processes, and other treatments target these systems. These approaches are often called “non-SMN” approaches. Many of these non-SMN approaches target the muscles or nerves.
Many researchers believe that it will take a combination of SMN-based and non-SMN treatments to provide the most benefit for those with SMA. This could mean that individuals with SMA will take two drugs together. Or they may take one type of treatment at one stage of the disease, and then another treatment at a different stage.
There is less consensus about whether combining two similar treatments—for example, two SMN-enhancing approaches or two non-SMN approaches that target the same system—will provide any additional benefit.
Timing is Key
Regardless of what type of treatment is selected, it is important that individuals with SMA begin therapy as soon after diagnosis as possible. This is especially critical for SMN-enhancing therapies. When SMN levels are low, motor neuron cells shrink and eventually die. In infants with the most severe form of SMA, 90% of motor neurons have been lost by six months of age. Once these neurons are lost, they cannot be regenerated.
Beginning therapy as early as possible is the only way to prevent or slow down motor neuron loss. For babies identified through newborn screening, treatment should ideally begin before the infant shows symptoms of SMA. In clinical trials of SMN-based therapies, infants and children who began treatment earlier had better results than those who began treatment later.
Currently, three SMN-enhancing treatments for SMA are approved by the U.S. Food and Drug Administration (FDA). The chart below describes these therapies. In addition to these approved treatments, several others are being evaluated in clinical trials.
For information on how you or your child may participate, please see here.
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|Description||Antisense oligonucleotide||Single stranded SMN1 DNA via adeno-associated virus (AAV9) vector||SMN-enhancing|
|Mechanism||SMN2 mRNA splicing modifier||SMN1 functional replacement with SMN1 DNA episome||SMN2 mRNA splicing modifier|
|Year of Approval||2016||2019||2020|
|Approved age||All||Less than two years old||All|
|Dose||12 mg/5 ml||1.1 × 1014 vector genomes/kg body weight||
Concentration: 0.75 mg/ml
|How given||Intrathecal bolus||Intravenous over 60 minutes||Enteral liquid (oral or feeding tube)|
|How often||Four loading doses over two months, then every four months||One time only||Daily|