CD38, a molecule whose origin dates back to almost a billion years ago and present in the human body, it could block the negative consequences of the Covid-19 infection. A possible cure such as the one already being used successfully to combat multiple myeloma is being studied.
How does it work
“CD38 is a very old molecule in the history of life: the human one was born 950 million years ago but the molecule is even more long-lived, it dates back to 4 billion years ago but we will keep this detail aside for now”, claimed exclusively for ilgiornale.it Fabio Malavasi, Emeritus Professor of Medical Genetics of the Department of Medical Sciences, Faculty of Medicine of the University of Turin. The important thing to know is what this molecule is currently used for. “It’s a target for the treatment of multiple myeloma, a neoplasm of plasma cells – says Prof. Malavasi – It is used because, usually, it is poorly expressed on the surfaces of normal cells while there is a lot of it on this tumor. For this reason, CD38 has been used as a therapeutic target for monoclonal antibodies which have represented a breakthrough in the therapy of this tumor “.
The role of CD38
The study, of which Prof. Malavasi is the coordinator, was published in the prestigious international journal Physiological Reviews (we have attached the original work, in Pdf, at the bottom of the piece). The researchers realized that there are particular situations that resemble what is observed live, that is on patients: “It has been observed that this molecule is also an enzyme that is on the surface of cells and is important because it regulates the synthesis of other factors. such as cytoplasmic signals that regulate calcium and other substances involved in inflammation “. And here comes the point: “we made a project for which, blocking this molecule in patients suffering from Covid, it would be possible to alleviate the most critical part which is the inflammation of the lung “. Flogosis means inflammation and it is when the lungs suffer due to the intestinal pneumonia typical of this disease. his staff analyzed and carried out a logical sequence based on what was observed in myeloma and transferred it to some patients by making an application project.
How Viruses Work
“This is because viruses go looking for molecules that apparently have nothing to do with them” – the geneticist tells us, explaining that viruses are “astute gentlemen who seek, within our cells, ways that are not practiced by anyone. Covid-19, for example, uses theAce2, a very common strategy in historical infections of recent years: think of the HiV that has chosen as its private receptor to enter the cells the CD4 molecule that marks the defense cells, so patients with type 1 HiV do not die from the disease itself but because they no longer have immunological defenses and it can happen that they die even from a simple cold. “These are all strategies adopted to bypass the cellular defenses of all types, immunological and serological, ie antibodies.
How Covid freezes
What will the research now be based on? “The research will focus on two aspects: on the one hand we have some antibodies that block the action of CD38 and it can be done through topical actions, in the lung itself, or with treatments by insufflating adenosine, a substance that inhibits the cytokine storm that is often the cause of death in Covid-19 patients. We try, in all possible and imaginable ways, to interfere with this storm. “One of the first suggestions was made using the interleukin 6 receptor because it was very reminiscent of the treatment of patients with Car-T cells or with antibodies: the goal of researchers is to interfere in the most normal and natural way possible with the emergence of these super inflammations, by extinguishing them. Blocking CD38 blocks the inflammation? “I would safely say that we can obtain an action that goes in that direction”, says Malavasi . At this point we expect the application in the “field”: to obtain it, however, it will take more months. “This is the problem we are working on, we have to make a ‘design’ in which our idea can be applied in some model in vitro and then in vivo, it will still take some time. For the cure, then, we will have to wait until 2022 “. Another question arises: how will the molecule be blocked, with a therapy or with a vaccine?” antibodies monoclonal agents are agents used as drugs that act on the CD38 target while vaccines are designed against viral components, this is the difference – explains the expert – All vaccines that are currently in use and under test, are directed against components of the surface of the virus and in that direction the immune response is directed. The antibody, on the other hand, is simply a protein that binds the target for which it is specific and blocks its functional activity, the ability to function as an enzyme. “
The molecule that is 4 billion years old
But let’s go back to the beginning, when Prof. Malavasi “put aside” the detail on this molecule born before man himself. How does it even be 4 billion years old? The story is curious and interesting. “In the history of life there is a continuous movement, this is why an analysis called phylogeny is made”: aplysia californica, for example, is a clam which far anticipates the presence of man in the history of life and is used in the laboratory to study the synaptic biological processes of learning and memory. What does aplysia have to do with, certainly unknown to most of us? “By studying it, a molecule very similar to human CD38 was discovered: this means that this molecule is very important for life because it works so well that it has never been changed, it plays a very important role in the history of life,” says Malavasi. CD38 is a 45 kilodalton surface molecule, an atomic mass unit widely used in physics and chemistry that is expressed with quantitative variability by many cell populations. “We could say ubiquitous at low density on all cells of the human organism: red blood cells have very little, lymphocytes more. However, inside the leukocytes there are plasma cells, those that produce antibodies, which have a very high presence on their surface: for this reason, the molecule was assumed as the therapeutic target of the antibody that kills the tumor target cell “, he concludes.