For the first time, the FDA (the US administration responsible for approving new drugs and equivalent to the European EMA) has approved an interference RNA-based therapy to treat hereditary transthyretin amyloidosis (ATTR).
ATTR is a rare disease that produces the accumulation of erroneous proteins in different organs, tissues or nerves, making it difficult to function and causing multiple symptoms that worsen the patient’s quality of life.
What does this disease consist of? What is interference RNA? How can it be used to treat amyloidosis?
What is hereditary transthyretin amyloidosis or ATTR?
Amyloidosis refers to a group of diseases all characterized by the accumulation of proteins in the form of amyloid. Amyloid is a material made up of erroneous proteins grouped into fibers (95%) and a series of substances that stabilize these fibers. This amyloid can be concentrated in different tissues and organs, producing its rigidity, and leading to its deterioration and insufficiency, which in turn can lead to the death of the affected person.
Within amyloidosis we have several subtypes, one of them is the hereditary form of the disease, whose errors in the affected proteins are transmitted between generations. Within familial amyloidosis, the transthyretin protein mutation is the most frequent cause and gives its name to the disease we are talking about today: hereditary transthyretin amyloidosis.
What is the interference RNA?
First, we must understand what RNA is, and for this, we must speak of DNA. Our genetic material is found in the form of DNA in each of the cells that make up our body. This DNA contains the information necessary to generate the proteins, responsible for the vast majority of functions in a cell. However, DNA is not converted directly to protein, but there is an intermediate step that is RNA. RNA is a sequence similar to DNA and from which proteins can be synthesized.
In other words, DNA is TRANSCRIBED into RNA as if it were an illegible text that needs to be revised in order to be read. Next, the RNA is TRANSLATED into protein, as if said text, after being revised and transcribed, we wanted to translate it into another language.
Well, what happens if we have a mutated gene? That the transcribed RNA will be wrong and therefore also the resulting protein. How can we prevent that erroneous or defective protein from being synthesized? Through interference RNA. This is nothing more than a copy of the faulty RNA, which when introduced at the cellular level will search for and pair with this erroneous sequence. This pairing will make the RNA unable to be translated into protein and therefore will block the appearance of these proteins.
How does this work in amyloidosis?
If the TTR gene, in charge of producing the transthyretin protein, has an error, the resulting protein will be incorrect and will accumulate in the form of amyloid causing the disease. How can we stop the accumulation of this incorrect protein? Generating an RNA identical to that of this protein. In this way, the interaction of both will block it and the formation of the wrong protein will be paralyzed, preventing its accumulation.
Did you know the interference RNA? As we have just verified, interference RNA has already begun to be useful as a treatment for this disease. Will it also be the solution to other problems? For the moment, the approval of this therapy gives the starting signal for this biotechnological technology to put an end to many other pathologies.