The development of mRNa vaccines, the first to arrive on the market to combat the Coronavirus pandemic, has opened a surprising new path. Not only in the panorama of world medicine, but in the collective consciences, more and more curious and less suspicious of an ultra-sophisticated technology that refers to antitodes that, at present, are considered indispensable, namely the Comirnaty by Pfizer / BionNTech and ‘mRna-1273 of Moderna. Few knew until now the bases of this genetic technique and, above all, its real potential.
More informed in this regard are probably those patients who struggle against insidious diseases, towards which genetic research has already been activated for years, with the aim of studying innovative and highly effective therapies, free from side effects as much as possible.
The RNA technique is in fact already adopted in various fields of medicine (in Italy, for example, there is a strong experience in the field of therapies for neoplastic diseases and has begun to work extensively also in the cardiovascular field) and can represent an effective and advantageous therapeutic future for tumor and haematological diseases as well as chronic degenerative and inflammatory diseases. Not only that: within a few years, thanks to the development of new definitive drugs “RNA silencers”, which require the administration of two doses (if not one) per year, this technology could also revolutionize the currently complicated treatment of arterial hypertension. To illustrate the steps taken so far, the new areas of research, the advantages and everything we can expect from now on from the development of RNA technology is Professor Claudio Borghi, Full Professor of Internal Medicine at the University of Bologna.
Professor, before the pandemic, very little was known about scientific research (and related treatments) focused on RNA technology. Why?
«The lack of information was due, in the first place, to the clear preponderance of traditional drugs. More recently, however, some knowledge of genetics, and above all the contribution of neoplastic diseases, haematological diseases and chronic inflammatory diseases, have shifted the target of the intervention to increasingly specific targets linked to cellular functioning mechanisms and in this case the possibility of interacting with nucleic acids, and in particular with RNA, became a reality that could be explored. First through a hybrid form of transition from traditional therapy to RNA technology, which was represented by monoclonal antibodies, which still have their relevance in many conditions but are directed against the RNA product, that is, in most cases, against a protein. Then, the attention shifted to the upstream process, in the belief that if it was possible to inhibit the circulating protein or tissue protein, it would also be possible to inhibit the protection process of this protein and in this situation RNA can play today. a substantial role “.
What are the strengths of this technology. What are the disadvantages?
«There are no great difficulties. This technology, which can be developed on a large scale, does not alter the genome because it does not deal with DNA, an extremely dangerous operation, but with the product of DNA.. It must be said that the experience in terms of years relating to the use of drugs produced with this technology is still relatively short, but all those developed in this area – and for some there is already evidence from a clinical point of view – have demonstrated the advantage of remaining effective with a single administration for a long period of time, without experiencing any side effects, which instead can be verified with traditional drugs which, not being “physiological”, interact with the disease through a substance that is fundamentally foreign to the organism ».
How long has science been investing time and resources in this area?
“In the context ofoncology andhematology we have been working on it for about ten years. In cardiovascular areaOn the other hand, research has received great impetus in the last 5 years, since it has been possible to identify therapeutic targets of which it was possible to inhibit protein synthesis and therefore in some way interact with RNA synthesis. Much has been concentrated on monoclonal antibodies, although it is a type of therapy that falls downstream of the RNA technique ».
What are the scientific fields on which attention is currently focused?
«In the cardio-metabolic field there are drugs that use this type of technology to control the lipid profile. One in particular is called Include, is already available in some countries and is about to go on sale in Italy as well if it manages to overcome the Aifa parameters and above all the rather difficult obstacle of the marketing price. It is about a drug capable of inhibiting high cholesterol levels, acting through an intermediate protein, thanks to a double annual administration. Means that two administrations per year of a small amount of this substance under the skin are able to maintain normal cholesterol levels, but the prospect is to further extend the interval of administration and to get to administer a single annual dose, obtaining a control of cholesterol levels distributed over twelve months. In this way, the main problem we have today with chronic therapy would be eliminated, namely adherence to treatment. Because not all patients take their drugs correctly and not all do it every day ».
It has often been heard that RNA technology can truly represent the new frontier in cancer treatment. Does this view correspond to reality?
«Definitely yes, even if in the field of neoplastic diseases, the first point always remains prevention, early diagnosis, a fundamental element that allows technology – any technology – to be effective. After that, of course, there are intermediate therapies that can identify or reduce the tumor mass. Thanks to the reading of the genetic profile of the neoplasms, and the identification of some specific markers that are in the neoplastic tissue, the creation of drugs with different characteristics has been favored, including RNA silencers that are able to abolish some proteins that cause the differentiation of cancer cells or that periodically allow them to be recognized by the residual immune system: the latter, sensing that it is in front of a foreign body, manages to eliminate it, thus fighting the growth and spread of the tumor. Basically, the RNA technique can silence the presence of proteins that can be potentially dangerous and responsible for the damage caused by certain diseases or, in some cases, also allow the overexpression of other proteins that move on a lateral side of counter-regulation. In practice, it means that on the one hand it is possible to reduce the impact capacity and on the other hand to act against the disappearance of inhibitors, increasing the availability of protective substances: two viable paths, which both pass through the technique of silencing the RNA “.
Is this a very expensive technology? Where does the research funding come from?
“The support funding comes largely from private research and from shareholders of some companies, often small, that develop only a few products. If they pass the screening of the preliminary analyzes of the clinical research development phases, they will be able to receive a sort of sharing from a larger company or, sometimes, the small companies can be completely acquired by larger companies able to support the production of their product. Furthermore, this technology has required huge investments in the order of billions of dollars. Some companies have also abandoned their research programs due to a lack of capital to conduct the studies but, thanks to the resilience of some companies, this technology has managed to become a therapeutic reality.».
Is Italy also investing in this sector? Are there any specialized research centers that are working in this area?
“In the cardiovascular and metabolic fields, we mainly receive information from other companies, mainly from the United States and partly from Germany. Italy, on the other hand, is very strong in the study of therapies for neoplastic diseases, both in adults and in children. Especially in the field of haematological diseases, there are drugs developed in our country that are having great success. In this case, however, I believe that the main collective effort is to globalize the potential for employment. It matters who generates one of these molecules but has the same support from an economic point of view, so that we can proceed from development to commercialization, because unfortunately the path of pharmacological research is very often paved with excellent products that fail to have a support to complete their research cycle ».
What specific field or disease is your team working on right now?
“Personally I am looking into the possibility of developing an RNA silencer that can revolutionize the therapy of arterial hypertension. Today our hypertensive patients take two or three tablets a day and this aspect has been partially mitigated by pre-established combinations of hypertensive drugs in a single tablet, so that multiple products can be ingested with a single drug; but there is still the need to take a pill every morning. Wanting to tackle arterial hypertension by borrowing what has been seen to date, an RNA silencer product is being developed which determines a sort of persistent “vaccination” over time ».
What are the future prospects linked to this area of research? Could RNA technology become preponderant?
“It is likely that it can become one for diseases with a tissue deviation such as cancer and haematological diseases and it is possible that it can also become so for chronic degenerative diseases, including the large field of chronic inflammatory diseases such as intestinal and osteoarticular diseases, rheumatoid arthritis, psoriatic arthritis: all conditions that could benefit from this type of treatment, thanks also to a limited number of administrations able to keep the disease under control, avoiding in patients with clinical complexity the increasing daily need to take from 8 to 10, sometimes 14 up to up to 20 different tablets a day to keep multiple diseases under control ».
A revolution. Over how many years?
“I’d say 5 years from now, because there are already data under development in the lipid world and others already available for some time for the most severe chronic degenerative diseases. Even in the context of hypertension, the process of pharmacological change could actually take place in the order of 5 years, also considering that this technology is able to travel very fast, especially if it will not encounter side effects, which today’s experience absolutely excludes. Once we have opened the way from this point of view, calculating that each protein is produced through the interaction between DNA and RNA, it is likely that we will have the opportunity to “turn off” some of the potentially unfavorable biochemical processes and consequently not only treat large pathologies but also related organ damage and those manifestations that are associated with the great chapters of medicine and in particular of metabolic cardiovascular medicine ».
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