2024-04-29 22:11:00
Progress does not stop with individual therapies: immunotherapy, CAR-T… Now, Europe is about to have the first drug based on CRISPR, a technology that results from genetic editing and promises to be effective against two diseases blood. .
Medicine tailored to the patient. What was once an entelechy, now turns out to be a reality in a state of expansion. For example, thanks to the discovery of the biomarker HER2Today, in clinical practice, there is a group of women with early-stage cancer who benefit from a very specific treatment, and the chance of eliminating the tumor is doubled. Before he could give this surname to the tumor, this part of the population received the prescribed treatment, which “not only did not have any benefits, but also gave them side effects. It was not effective at all ,” says Carlos Sisternas, director of the Spanish Federation of Health Technology Companies (Fenin) of Catalonia.
This is what personalized medicine is all about. It consists of designing a specific medication menu, «according to the individual characteristics of each patient». That is one of the great challenges of medicine: to achieve more effective individualized drugs, with fewer side effects and able to increase the survival of people with metastases, improve their quality of life and save the health system with 25,000 euros per patient, according to an estimate of some work done by the American National Institutes of Health (NIH).
Therefore, says Sisternas, “technology for molecular diagnosis and massive sequencing panels, as well as the abundance of equipment in clinical analysis and pathological anatomy laboratories, are essential.” Thanks to them, Researchers around the world have been studying the genome for over twenty years to learn more and more about changes which occurs in various diseases. In this way, it is possible to work on the development of drugs that act selectively, blocking the damaged gene and, therefore, affecting the progression of the pathology and the survival of the person concerned.
It was in 2003 that, after many years of effort, the essential sequence of our DNA was interpreted for the first time. It was a real milestone, although it did not bring all the information about the genome together. There were some gaps that are being dissolved, gradually and with the technological improvements that are taking place.
In the study of this cartography, genetic changes associated with various diseases are found, and in addition Improving the differential diagnosis makes a big difference in the patient’s prognosis. Returning to the example of HER2 positive breast cancer, based on the analysis of the tumor sample, if the medical team identifies the said genetic change in HER2 (which occurs in 18%-20% of cases), a significant improvement in the outlook. Treatment directed against HER2 (anti-HER2 therapy) produces few side effects.
He too Lung cancer shows great progress thanks to personalized medicine. About 15% of those affected, generally non-smokers, carry mutations in the EGFR – Epidermal Growth Factor – and ALK genes. In a standardized way, the possible presence of these mutations is analyzed in metastatic patients. When they are positive, the treatment indicated would not be chemotherapy but specific inhibitors of these changes. Therefore, the therapy manages to inhibit the functioning of tumor cells and, therefore, prevents the growth of the lesion. With chemo, 40% of patients respond and the average survival is 12 months.
A paradigm shift
Actually, the door opened with the chronic myeloid leukemia. According to Ismael Buño, scientific director of the Gregorio Marañón Health Research Institute (IiSGM), “it was the first tumor in which a causal genetic change was discovered (the Philadelphia chromosome was discovered by two scientists from this American city in 1960: Peter Nowell and David Hungerdorf) and the first in which a specific inhibitor was developed as a treatment. These are called therapies directed at molecular targets.
If patients with this disease were condemned to death before, now their quality of life is almost the same as the rest of the healthy population of their age. “This progress was the path of what we should do, the beginning of the new medicine,” says Buño. “Personalized medicine comes from the world of genomics, it was born with biomarkers.”
The concept of genetic biomarker It refers to a fraction of DNA, which represents the characteristics of each person. Today, its use is one of the most important clinical tools in precision medicine. It is especially true in oncological diseases, but also in the diagnosis and treatment of rare diseases.
It is worth remembering the case of Judy Perkins, a woman with metastatic breast cancer the doctors considered it hopeless. With various tumors spreading throughout his body, Perkins underwent experimental treatment at the National Institute of Health in Bethesda (Maryland, USA) based on T cell immunotherapy, very personal therapy. The researchers sequenced the DNA and RNA from one of her tumors, as well as normal tissue, with the goal of checking which mutations were unique to her cancer. They identified 62 different mutations in their tumor cells.
Then, through complex engineering work, they selected the most powerful T lymphocytes from Perkins’ own immune system to grow them in large quantities in the laboratory and direct them towards the proteins caused by the mutated gene and expressed on the surface of the cells malignant . About 90,000 million immune cells were the ones the patient received by injection, along with two other drugs: interleukin and pembrolizumab. What this medication does is prevent the immune system from falling asleep and acting against tumor cells. Although this effect did not give enough results on breast cancer, the clinical trial worked. After a week, the tumor shrunk and experts started talking about remission.
The IS immunotherapy It uses the patient’s own immune system to fight the disease. Another of the great advances in personalized medicine is based on this premise: CAR-T. They consist of removing lymphocytes to genetically modify them to reintroduce them into the patient so that they can recognize and attack cancer cells. These therapies have achieved important results in hematological tumors and are expanding their effects further. Positive response rates are already starting to be published in solids, such as HER2-positive breast cancer.
Regarding CRISPR, at the end of 2023, all the media echoed the proposal from the European Medicines Agency to authorize a treatment based on this genome editing therapy. Its name: Casgevy, effective against sickle cell anemia and beta thalassemia, two potentially fatal blood diseases. The drug already had the approval of the regulatory agencies of the United Kingdom and the United States. It is expected that the European Commission will give a green light to its commercialization soon.
CRISPR’s major revolution lies in its ability to correct DNA errors. It is a genetic engineering technique that allows the genome of any cell to be corrected and edited. Thanks to this tool, researchers Jennifer Dounda and Emmanuelle Charpentier won the Nobel Prize in Chemistry in 2020.
It is called the molecular scissors, because they act by cutting and gluing fragments of genetic material. This genetic cut and paste has shown promise as a therapeutic approach to treat rare acquired diseases. However, most gene editing strategies focus on correcting specific mutations that only occur in a small group of patients before the onset of the disease.
At the beginning of last year, a study published in the journal Science found good results in more common pathology, in cardiology, specifically, in the repair of ischemia-reperfusion injuries, which cause other ailments such as myocardial infarction. The experiment changed mouse hearts, so there is still time to expand the application of this genetic technique.
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