2023-10-30 20:17:14
More than 5,000 people receive an organ every year in Spain. The volume of transplants has grown exponentially. Organ extraction and preservation techniques have also improved while surgical techniques have been developed that reduce the aggressiveness of surgery. But there is still a challenge in research: the improvement of immunosuppressive treatmentsthose drugs that ensure that transplant recipients recognize their new organ as their own and do not reject the heart, kidney, lung or liver that has just been transplanted.
These medications work, but trigger cardiovascular risk. They promote the concentration of cholesterol and triglycerides in the blood, raise blood pressure and the appearance of type 2 diabetes, all ingredients that predispose to stroke or heart attack. Hence the importance of finding new treatments for transplant recipients.
The Vall d’Hebron Hospital Research Institute in Barcelona is working, with funding from the La Caixa Foundation, on the development of a new immunosuppressive medication to prevent rejection without these side effects. «We were looking for a drug that, in addition, would most likely have the advantage of being administered only biweekly and subcutaneously. This would improve the quality of life of the patients and reduce the problems of adherence to treatment that exist with immunosuppressive drugs taken daily and orally,” he explains. Oriol Bestardproject leader.
His team already has a candidate: an immunosuppressive molecule, structurally modified to increase its immunomodulatory properties and avoid rejection by canceling the activity of T and B cells. These cells are responsible for the human body rejecting what it does not recognize as its own. . Unlike current medications, the molecule under investigation does its job by freely entering cells. «It is a fundamental advantage for our drug since it only exerts its specific function in cells that have the corresponding receptors (its ligands), and not in other cells in the body. In this way, it minimizes unwanted effects since it will only exert its specific effect for which it has been designed and not through its interaction with other cells in the body,” says Bestard.
Preliminary phase
The beginning is promising but the molecule has yet to demonstrate its effectiveness, beyond the laboratory. Its development is in a very preliminary phase and it will take years to reach pharmacies. The next step will be to test the new treatment in experimental animal models. They will do it thanks to a grant of 148,500 euros from the La Caixa Foundation. Its effectiveness will be evaluated and performance studies will be carried out, including the development of a stable production line for the drug.
The new molecule will be tested in mouse models that will receive a heart from another genetically incompatible mouse. This means that the organ will be quickly rejected if immunosuppressive treatment is not provided.
It is expected to corroborate the results in animal models over the next two years, as well as carry out a toxicological analysis of the drug, before undertaking the first clinical trials of safety and efficacy in real patients. A formula may be found first so as not to depend on any immunosuppressive medication.
Immune tolerance
For years, doctors and scientists have entertained the idea of inducing immunological tolerance in these patients that would allow them to do without them. It all started with the observation of some patients who spontaneously abandoned medication due to psychiatric problems, lack of money or simply because of fatigue. Against all odds, when they stopped immunosuppression, nothing happened to them. Those transplanted continued to live without their body rejecting the transplanted organ, as if it had been incorporated as another part of their body.
Some cases have been seen in kidney transplant recipients, but especially in the liver, an organ that requires less medication than others. It is estimated that 30% of people living with another person’s liver would not need treatment to avoid rejection. The question is knowing who could abandon it without the risk of losing the organ that allows them to continue living.
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