What is SMA?
SMA is short for Spinal Muscular Atrophy, a hereditary muscular disease that causes muscles to function insufficiently or not at all. SMA is categorised into four types: type 1 to 4. Which type it concerns, depends on the age at which the disease is diagnosed.
SMA type 1 is the most serious form, with symptoms appearing at birth or shortly thereafter. An increase in the number of motor neurons in the spinal cord that are not working properly, results in progressive muscle paralysis. The muscles become weaker and weaker (atrophy).
In many cases, babies with SMA 1 can only move their hands and feet. Deterioration happens so fast that most children die before the age of two. As a rule, the earlier the onset of the disease, the more severely it progresses.
What causes SMA?
SMA is caused by a fault in a piece of genetic material (DNA), the SMN1 gene. This gene is responsible for the production of the protein SMN. This protein controls the proper functioning of the motor neurons in the spinal cord, which is essential for the transmission of signals from the brain to the muscles. In case of a shortage of this SMN protein these cells do not function properly or not at all, due to which no signals or inadequate signals are sent to the muscles. This causes muscles to wither and eventually results in paralysis.
The illustration above (UMC Utrecht, 2020) is a schematic representation of how SMA occurs: the SMN1 gene doesn’t function properly, causing insufficient amounts of the SMN protein to be produced. As a result, motor neurons, which control movement, do not function as they should and break down. The ultimate result is loss of muscle strength, which makes it difficult to move.
People also have an extra version of the SMN1 gene in their DNA in de form of the SMN2 gene. Although this ‘extra gene’ also produces the SMN protein, unfortunately it doesn’t work as well as the SMN1 gene. Only a limited amount (around 10%) of the SMN protein produced by the SMN2 gene is effective, the rest is useless.
The illustration above (UMC Utrecht, 2020) shows the SMN1 and SMN2 genes. It demonstrates that the SMN2 gene is far less effective in producing the SMN protein. Only about 10% of the output of the SMN2 gene is the correct SMN protein. The remaining output (about 90%) is broken down rapidly because it is not effective. In people with SMA, the SMN1 gene doesn’t work (right side of the illustration).
Treatment of SMA
Unfortunately, at present there is no cure for SMA type 1. The treatment is aimed at relieving symptoms and slowing down deterioration.
Spinraza® (Biogen) is the first, and currently the only, approved treatment available in the Netherlands for children with SMA type 1. Treatment with Spinraza® is a complicated process. It can only be administered by means of an epidural. In the first year, a baby must have six injections, four of which in a period of two months. After the first year, children receive three doses of the drug per year for the rest of their lives.
Spinraza® affects the SMN2 gene by boosting its protein production and, thus, causing the motor neurons to stay healthy. This halts the disease.
But there is hope! There is now a promising new drug named Zolgensma®. This is a one-time viral gene therapy that inserts the missing SMN1 gene. The results of the first trials with this drug are very promising. It should enable children with SMA type 1 to live a long and wonderful life in which they may be able to learn to walk and be much more independent. However, there is one major problem: Zolgensma is the most expensive drug in the world. It costs 1.9 million euros.