construction of a protein called SMN . Its name comes from the suggestive acronym survival of motor neuron , and it plays very important roles in our body . In fact , without SMNs , there is no survival of motor neurons , and no possibility of life itself . This is because these cells are essential for carrying out muscle movements , including those of the diaphragm or pharynx , which allow us to breathe and eat .
So how do SMA patients survive ? Because it turns out that there is a second gene in the human genome , called SMN2 , which also allows us to build the same SMN protein . SMN1 and SMN2 are almost identical , but SMN2 differs in five of the more than 40 000 letters or nucleotides of which these genes are composed .
The existence of virtually identical genes is very rare in the human genome . In fact , SMN2 does not even exist in other animals : it is unique to our species .
A lifesaver
These minimal differences between the two genes mean that the SMN protein from SMN2 is only produced in its entirety in 10 % of cases . In principle , this would be insufficient for long-term survival , but it happens that humans can have from zero to more than ten copies of the SMN2 gene .
Doing a quick calculation , if we have ten copies , and each copy produces 10 % of SMN , we will generate 100 % of the SMN protein we need . But what happens if we have fewer copies of SMN2 , say five ? Well , only 50 % of the required SMN is made up .
So , in general , those who lack the SMN1 gene and have only one copy of SMN2 have a severe case of the disease , with more rapid progression ( type I ). Those with two copies have a milder case ( type II ). Finally , with three or more copies we have an even milder case ( type III ) and the chances of living longer are increased .
Given this reality , we can conclude that evolution “ invented ” the copy of SMN1 in humans to have a lifesaver in the case of losing the main gene . Beautiful , isn ’ t it ?
Extortionately expensive treatments
Knowing all we know , how can we cure SMA ? If SMN1 is missing or the gene is mutated , as with other genetic diseases , there is no choice but to replace the missing gene . In fact , although it sounds like science fiction , this substitution is already underway . In 2019 , the drug Zolgensma was approved , which allows the SMN1 gene to be introduced via a virus that carries it directly to the motor neurons .
But the real beauty of SMA is that , because SMN2 exists , we can use other , more original approaches . Let ’ s think about it for a moment : if we can figure out what makes SMN2 produce only 10 % of the full SMN protein and fix the problem so that the percentage is higher , we can compensate for the lack of SMN1 .
And that ’ s what the first treatment approved in 2016 for SMA , Nusinersen , does , as well as another one greenlit in 2020 , Risdiplam .
What these treatments achieve seems really easy to do if we rely on a bit of basic biology . In the case of Zolgensma , it ’ s all about getting the SMN1 gene intact into the motor neurons , which is now called gene therapy . And in the case of the other two treatments , the challenge is to get something to stick to the region that differentiates SMN1 and SMN2 , to turn the latter into the former .
But the difficulty of making this work , and also bringing it to the rare disease market , means that both treatments are among the most expensive in the world . Zolgensma costs no less than …. two million euros per dose ! That makes it the
To Table of Contents
Accessibilty for All 53