Spinal Muscular Atrophy Treatment
Recap: What is SMA?
Spinal Muscular Atrophy (SMA) is a genetic condition that impairs the ability to move due to muscle weakening. The severity of the condition and it’s carrier frequency being quite high makes it surprising that it is not that known by the general public. SMA is the second most common genetic cause of infant mortality, with 1 in 50 people being carriers and an incidence of 1 in 10,000 births.
Currently websites will say that there is no current possible cure to SMA, however major advances have been made in recent years which could be life changing. Traditionally, supportive treatment has been available. Exercise and equipment to help breathing and movement is necessary, patients are given feeding tubes to help with meals and are provided with dietary advice. Braces and surgery can be given to treat spinal and joint problems.
To understand where ideas from treatment have come from, we must understand the genetics of the condition a little more…
As we have already discussed, the condition is caused by a mutation in the SMN gene. But the SMN gene has two copies; SMN1 and SM2. SMN1 is the determining factor for the disease, as in SMA patients, it is missing. All SMA patients have SMN2, which can produce SMN protein, but to varying extents. SMN1, which is missing in SMA patients, makes full length protein and SMN2 makes 10% of full length protein. By 10% we mean, when mRNA is being translated to make proteins, 10% of the type, full length protein will be made, and this happens due to alternative splicing. If you need a little help getting your head around this, look at the image above.
So therefore, as you may have guessed, SMA severity is down to SMN protein levels. All types of SMA are caused by the same mutation, but having SMN2 protein makes it a treatable disease. If you have more copies of SMN2 then you have more mild form of the disease. Therefore type 2 patients make twice as much SMN protein as type 1 patients.
So the idea for treatment is then to raise the levels of SMN protein in patients. Spinraza is a new, recently approved by FDA, prescription medicine that works by increasing the ability of SMN2 gene to make full length protein.
‘Spinraza contains an antisense oligonucleotide — a molecule that works by increasing the body’s ability to produce a protein called survival motor neuron (SMN), which is essential for motor neuron health.’
Spinraza increases SMN2 gene’s ability to produce full-length SMN protein. It does this by binding to the SMN2 mRNA, which is a copy of the SMN2 gene that the cell’s ribosomes translates to produce the protein. Spinraza covers up the signal that causes the shorter than normal protein (which is what normally happens) to be made and allows the mRNA from the SMN2 gene to be full length, similar to the way the mRNA would normally be made from the SMN1 gene.