2023-12-26 03:24:47
María Luz Martínez-Chantar, where everyone at the research center CIC bioGune from Derio (Vizcaya) known as Malu, it is full. Her project, a new technique that, thanks to RNA, promises to combat incurable liver diseases, has just received a grant of 150,000 euros from the ‘La Caixa’ Foundation. The innovative treatment has already proven effective in laboratory trials, and now she dreams of using that money to complete the regulatory phase and validate what could be the treatment of the future for many patients.
Because most likely the joy that the project is bringing to the entire team is the closest thing to a dream for any scientist. The work began in 2005. That year Malu took charge of the ‘Liver Disease Lab’, one of the laboratories that make up the scientific ecosystem of CICBiogune of Vizcaya. His research focused on finding a cure for liver diseases and it was the acuity of his eye that detected that, between microscopes and Petri dishes, the key could be in magnesium, a compound that appeared altered in all patients. . “We wanted to identify whether the magnesium alterations we saw in patients with liver diseases were due to adipose tissue or whether the liver had something to say,” he explains. To do this, they launched a “very, very exhaustive” study that led them to the molecule that hid the key to the entire process.
This is the CNNM4 transporter, a molecule that transports magnesium in the human body and that appeared “especially induced” in patients with liver damage. The pattern was the same, he explains, whether they suffered from fatty liver, alcohol damage, cholagiocarcinoma, or paracetamol overdose damage. “Once we detected this pattern, we wanted to see what happened when healthy hepatocytes (liver cells) were overexposed to the levels of this transporter,” he says, and his laboratory mice revealed that it was CNNM4 that caused liver damage. That is, the transporter did not appear as a consequence of a damaged liver, but rather it was the “conductor” that made the organ sick.
Martínez-Chantar and his team were clear that the solution was to find a very specific system that could “silence”, or at least “modulate” the activity of that molecule in the liver, without affecting the function it could have in others. body parts. It is at this point in the research, he relates with great didactic ability, where messenger RNA technology provided the icing on the cake of the research. Because, although it is the ‘fashionable’ treatment in modern medicine, after the success of the vaccines against covid-19 or the awarding of the Nobel Prize in Medicine to the creators of this technology, in the ‘Liver Disease Lab’ it had been a long time who were experimenting with it. “We thought that the best approach was to use a therapeutic RNA capable of reducing the levels of that molecule in the liver cell,” he explains.
Four thousand tests
When she tells it, it seems like a simple process, but finding the ideal molecule cost the team of a dozen researchers more than 4,000 tests. Thus, they managed to combine an RNA capable of reducing the CNNM4 transporter in the liver with GalNAc, a sugar widely used in biochemistry for its ability to combine. They were years of trial and error, Martínez-Chantar recalls, which would not have come to fruition without the teamwork and collaboration of Naroa Goikoetxea, Malu’s right-hand man these years and who will also be in the company that develops the project. “It was complicated because we wanted it to act on the CNNM4 transporter, without touching the expression of another gene,” she summarizes.
But they finally managed to find a “very stable” molecule that lasts up to “four weeks” in the body and that is inoculated with a subcutaneous injection, “as if it were heparin.” Once injected, it travels to the liver, where there is a receptor capable of recognizing it and thus “manages to modulate the expression of the gene that is causing this damage.” As a consequence, in the trials carried out so far it manages to reverse the damage of pathologies that until now lack effective treatments with “very small” side effects.
Towards personalized medicine
Although the importance of its creation goes beyond helping liver patients. Martínez-Chantar is clear that therapeutic RNA is part of the “therapies of the future.” Even, why not, he dares to “dream” of it being the first step of personalized medicine that manages to act on genes that cause incurable pathologies with fewer effects than conventional drugs. “Because it is so specific, we are directing it specifically to the organ and cell that we want,” he explains.
A dream that seems gigantic and which from its small laboratory would now like to do its bit. With the subsidy from ‘La Caixa’ he hopes to found the company that will allow us to “close the circle” that any scientist longs for and be able to develop the treatment. “For me and my team, the training that accompanies the program is being essential, to open our eyes and see where the resources are,” he acknowledges. And for his joy to be complete, he still has a long way to go.
The molecule that has been proven effective will now have to pass tests by certified laboratories that will verify both its effects and the absence of toxicological damage. And then it will have to pass clinical trials, “around five or six years in total.” Meanwhile, they are already working to see if their technique can also be effective in diseases such as pulmonary fibrosis or kidney fibrosis, where abnormal levels of the magnesium transporter have also been detected. “So far we have been able to generate a molecule to treat it and in the future we will have to see if it also works in the clinic with patients,” he concludes.
1703562109
#RNA #medicine #future #step #personalized #medicine