Dr. Valentina Bonetto, head of the Sla Center of the Mario Negri Institute: “Personalized ASO therapy is targeted”
In a few months Matteo Materazzi lost the use of the legs, ending up in the wheelchair. And today he doesn’t even move his arms anymore, just a little hands. “The disease is advanced quickly,” Maura Soldati, the prosecutor’s wife, said. For years the ALS have called it the dark evil of the ball. There are those who spoke of a link with pesticides, because the exposure would increase its risk. And there are also those who have questioned themselves on doping, but without any scientific evidence to support. Matteo, brother of Marco, world champion 2006, and champion of everything with Inter, put the link between football and Sla at the center of the chronicles. His wife, in an interview with Corriere della Sera, said he launched a fundraiser (they reached 200 thousand euros) because “we only have hope, create a personalized ASO therapy for the rare mutation that hit him”.
therapy
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But what is an ASO therapy? A fragment of DNA or RNA, explains Dr. Valentina Bonetto, head of the Sla Center of the Mario Negri Institute, “which is able to inhibit the production of a toxic protein by intervening directly on the ARA. When a gene suffers a mutation, it can begin to produce proteins harmful to the body. The ASO (oligonucleotide antistheno) blocks the synthesis of that changed protein. targeted therapy, which acts on the genetic mutation by preventing the production of the toxic protein “. Imagine as a special patch that attacks the wrong message inside the cells and blocks the production of a bad protein. We need when a gene is defective.
therapies
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In ALS there may be many different errors, so many different patches are needed, one for each error. In the SLA, Bonetto goes on, “over 30 changed genes have been identified. Therefore, to use the ASO, over 30 different therapies would be needed”. An ASO therapy, for example, is Tofersen, has been approved for patients with mutation in the SOD1 gene. “Inhibiting this gene is not risky – explains the researcher -, because it is not essential for the body. This therapy has worked because, after decades of laboratory studies, it has been seen that blocking that protein has no side effects”. But for SLA patients, who do not have a sod1 mutation, things are much more complicated. “Only 10% of ALS patients have a genetic form,” explains Bonetto. The mutation, for example, may concern a fundamental gene: inhibiting it could be dangerous. It was the same wife of Materazzi, during the interview, to speak of “one more difficulty”, that is, that “the protein that accumulates in neuronal cells and that intoxicity is also functional to the cell itself. Which makes the search for a more difficult cure”. The mutation that Materazzi has, therefore, could be present in less than 1% of the sick and this creates further difficulties and problems for care.
in America
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The Materazzi family turned to Columbia University. And to Dr. Neil Shneider, a lumarer, who has studied, experiments and seeks a way to get out of the dark labyrinth of this rare disease from all life. After Tofersen’s success, Bonetto explains, “Aso are developing for rarer mutations. But many of these genes are important for the cell, therefore intervening is more risky. We try to hit only the changed part of the gene, with a personalized approach. According to reports from Materazzi’s wife, its mutation concerns a protein too important to be blocked without risk. These are still experimental and pioneering therapies, supported. From limited data, but the first positive results are not lacking.
costs
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Then there is the problem of costs, and it is no small thing. The crowfounding of the Materazzi family will serve to cushion everything. The expenses are many. Because, the wife said, “one and a half million dollars are needed.” And of course time. A year, at least. “But who knows if we have it.” Certainly Columbia is at the forefront of these new therapies and this gives hope. Columbia has shown promising results on the Fus gene, although the results have not yet been officially approved. The limit is the cost: here we talk about the development of a therapy for a single patient. In Italy there is public health and considering costs becomes difficult. But in the rare disease sector, the costs are enormous. In the United States, an operation can cost hundreds of thousands of euros. However, the Materazzi family is determined. The goal, said Soldati again, “is to save the life of my husband and those who in the future will face the same disease. I also think of our children, 18 years old and Gianfilippo of 16, who have between 15 and 20% of the possibility of developing the same mutation”. In Italy research is investing in the sector. And doctors are looking for early signs to know who could get sick. Because care work even better if they start before symptoms appear. So you study the cells to find what changes, what changes, what’s that connects different cases. They are biomarkers, small signals or clues in the body that tell us if something is wrong, or if it could go wrong in the future.
Research and future
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Finding them would allow, once the therapy has developed, to create treatments for all SLA patients, not just those who have a defective gene. “Research aims to identify early biomarkers, even non -genetic, which can report an increased risk of developing the disease. This is because the therapies are more effective if administered before the appearance of the symptoms or in the very initial phases. Genetic tests can be useful, but if a known mutation is not identified, it is difficult to make an early diagnosis. For this reason, patients with healthy cells are being compared to recognize the signals, with the aim of recognizing the signals Initials of the disease. Artificial intelligence is helping. It is useful in analyzing data, in research, and above all in cucoking the times. “But works on already known information”, Bonetto goes on. “Scientific creativity is still human. In the future, perhaps it will be able to formulate theories, but today supports, does not replace, the researcher. Thanks to new technologies, research times have shortened. Especially in rare diseases, however, they remain unpredictable and depend on many factors. The IA allows you to analyze large quantities of data and speeds up processes, but cannot respond to everything”.
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