What occurs, basically, is that my motor neurons (the “cable televisions” that connect the spine cable to the muscles) gradually degenerate and end up dying. This has actually kept me in a wheelchair for the majority of my life. And gradually, the involvement of the respiratory muscles can lead to the deadly outcome.
But given that I am also a scientist, I must include that I have discovered that SMA is the most lovely disease worldwide … at a molecular level.
My name is Antonio and I experience spine muscular atrophy (SMA, for good friends). My life span was just a couple of years when I was born, nearly half a century earlier. And all since I “got” an unusual, neurodegenerative illness, which is amongst the hereditary diseases with the greatest associated mortality.
How does back muscular atrophy occur?
Doing a quick computation, if we have ten copies, and each copy produces 10% of SMN, we will produce 100% of the SMN protein we need. What occurs if we have less copies of SMN2, state five? Well, only 50% of the required SMN is comprised.
The presence of practically similar genes is very rare in the human genome. SMN2 does not even exist in other animals: it is distinct to our types.
In general, those who do not have the SMN1 gene and have only one copy of SMN2 have a serious case of the illness, with more rapid progression (type I). Those with 2 copies have a milder case (type II). Finally, with three or more copies we have an even milder case (type III) and the opportunities of living longer are increased.
Offered this reality, we can conclude that advancement “developed” the copy of SMN1 in humans to have a lifesaver when it comes to losing the main gene. Beautiful, isnt it?
This gene contains the details to guide the construction of a protein called SMN. Its name comes from the suggestive acronym survival of motor nerve cell, and it plays extremely important functions in our body. Without SMNs, there is no survival of motor neurons, and no possibility of life itself. This is since these cells are essential for performing muscle movements, consisting of those of the diaphragm or vocal cords, which allow us to eat and breathe.
SMA is a genetic disease triggered by the mutation or loss of a gene called SMN1. If our mother and daddy have actually a mutated copy (one of 2 copies each), and we are unfortunate enough to acquire these 2 defective copies, we are likely to get SMA.
These very little distinctions in between the 2 genes mean that the SMN protein from SMN2 is just produced in its whole in 10% of cases. In principle, this would be insufficient for long-lasting survival, however it occurs that humans can have from absolutely no to more than 10 copies of the SMN2 gene.
How do SMA clients make it through? Since it ends up that there is a 2nd gene in the human genome, called SMN2, which also enables us to build the exact same SMN protein. SMN1 and SMN2 are practically similar, but SMN2 differs in 5 of the more than 40 000 letters or nucleotides of which these genes are made up.
A lifesaver
Extortionately expensive treatments
If we rely on a bit of fundamental biology, what these treatments accomplish appears actually easy to do. When it comes to Zolgensma, its all about getting the SMN1 gene undamaged into the motor nerve cells, which is now called gene treatment. And when it comes to the other two treatments, the challenge is to get something to adhere to the region that differentiates SMN1 and SMN2, to turn the latter into the former.
But the genuine appeal of SMA is that, because SMN2 exists, we can use other, more original methods. Lets think of it for a minute: if we can find out what makes SMN2 produce only 10% of the full SMN protein and fix the problem so that the portion is greater, we can make up for the absence of SMN1.
Why these sky-high rates? We will never ever know. Pharmaceutical business generally negotiate the rate of the drug separately in each country and with no openness. This leads them to consider the drug as a commodity, the price of which is not necessarily connected to its advancement and production cost. Rather, it is the cost one wants to spend for the life and wellness of clients in every part of the world.
And thats what the first treatment authorized in 2016 for SMA, Nusinersen, does, along with another one greenlit in 2020, Risdiplam.
The problem of making this work, and likewise bringing it to the rare illness market, suggests that both treatments are amongst the most expensive in the world. That makes it the most costly disease in the world.
By the way, none of the three drugs treatments. They just slow down the development of the illness– which is no small thing.
Knowing all we understand, how can we treat SMA? If SMN1 is missing or the gene is mutated, as with other genetic illness, there is no choice but to change the missing gene. In reality, although it seems like science fiction, this replacement is already underway. In 2019, the drug Zolgensma was approved, which enables the SMN1 gene to be introduced through a virus that brings it straight to the motor nerve cells.
Future for SMA and other rare diseases
Antonio J. Pérez Pulido, Profesor Titular de Universidad e Investigador en Bioinformática, Universidad Pablo de Olavide
In conclusion, it is indisputable that SMA is a terrible illness, which SMA patients will always can complain about the misfortune we were born with. At least I hope I have actually shown that this illness has an unique beauty at the molecular level which, for those of us who suffer from it, also gives us a specific right to call it “the most gorgeous illness in the world”.
This post is republished from The Conversation under a Creative Commons license. Read the original post.
On the other hand, we can pin our hopes on drug repurposing, i.e. the usage of existing drugs for other diseases. This has the massive advantage of significantly decreasing costs and reducing research times.
What will take place in the future with these unusual disease treatments? Treatments such as gene treatment have actually currently been used for other illness, and will unquestionably continue to appear and, more importantly, to be improved.
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In general, those who do not have the SMN1 gene and have just one copy of SMN2 have an extreme case of the disease, with more quick progression (type I). If SMN1 is missing or the gene is mutated, as with other genetic illness, there is no option however to change the missing gene. The trouble of making this work, and likewise bringing it to the uncommon illness market, means that both treatments are amongst the most expensive in the world. Treatments such as gene therapy have actually currently been used for other illness, and will unquestionably continue to appear and, more significantly, to be perfected.
And all because I “got” a rare, neurodegenerative illness, which is amongst the genetic illness with the greatest associated death.