A team from the Research Unit of the University Hospital of Gran Canaria Doctor Negrín will participate in the first clinical trial of lung transplantation with ozone to prevent chronic rejection. And it is that the good results obtained in a study with rats led by Gran Canaria doctor Norberto Santana Rodríguez, head of the Thoracic Surgery Service of the King Faisal Specialist Hospital & Research Center, in Riyadh –Saudi Arabia–, have led experts to go one step further and test the effects of this gas on humans. The initiative is expected to start in early 2022 and involve between 50 and 60 patients, who will be under medical follow-up for three years.
«This research project with ozone in lung transplantation is part of the translational research circuit that my group and I started in Negrín in 2003. First, we identify the most frequent problems of this type of transplantation in clinical practice, being chronic rejection the main cause of long-term death. Then we tried to understand at the genetic and molecular levels what chronic rejection was. When we discovered the genes that were involved, we tried to find a treatment, so we opted for ozone to tackle oxidative stress –a process that occurs due to an excess of free radicals– ”, explains the doctor.
The road has been long. First, an experimental model had to be created that was reliable and reproducible in animals.. «There were very few groups in the world doing this transplant in rats, since it is a very complex microsurgical practice. We got down to it and in 2004 we published the first scientific article that guaranteed that the model was viable, ”says the specialist. ´
The team continued to make modifications to make it increasingly similar to human lung transplantation. “When we had it well defined, we opted for a very ambitious project that focused on studying the genes and molecular pathways that were involved in chronic rejection, using DNA microarrays, a leading technology worldwide at that time. Thanks to it, we analyzed 40,000 genes and hundreds of molecular pathways, which allowed us to discover in 2011 that oxidative stress was involved in chronic rejection. The article was published in the magazine The Journal of Heart and Lung Transplantation.
Three years later, the researchers involved designed a study with 36 rats, which were divided into two groups. "One of the groups was transplanted and did not receive treatment, while the other was transplanted and received ozone treatment for three months," says the thoracic surgeon. The results were clear: All the animals that did not receive ozone suffered severe chronic rejection, while among those that did receive it, there were no cases and only a very mild acute rejection occurred. «The article was published in 2017 in the magazine Annals of Thoracic Surgery and it had a lot of impact. Since then, we have been looking for a way to extrapolate these experimental results to humans, ”says Dr. Santana.
The project is the result of the good results obtained in a study with rats
Now is the time to take on that challenge. To conquer the goal, Dr. María Dolores Fiuza, specialist in Epidemiology in the Research unit of the Hospital Universitario de Gran Canaria Doctor Negrín and technical secretary of the Ethical Committee for Research with Medicines of the province of Las Palmas, will be in charge of methodological coordination. «All participating hospitals must pass on their patients' data to us. However, from this center we will carry out other functions inherent to clinical trials so that mistakes are not made when selecting the participants and that the information arrives appropriately, ”says the professional. To this must be added a correct analysis of the results that guarantees that the investigation is carried out satisfactorily.
The essay, which is currently in the drafting phase, will be evaluated by the Las Palmas Research Ethics Committee, which is nationally and internationally accredited. "There will be a technical-scientific evaluation, another ethical evaluation and then an opinion will be issued that will serve the rest of the world," he clarifies.
The initiative will be evaluated by the Research Ethics Committee of Las Palmas
The expectations are high. In addition, in Fiuza's opinion, the fact that a Canarian hospital participates in a trial of this kind will contribute to position the Archipelago worldwide. “This will enhance our excellence because we are capable of conducting pioneering clinical trials in the world. We have very brilliant researchers in our autonomous community who, like Dr. Norberto Santana, have to go abroad, but he has managed to keep his research team together from a distance ", he values.
The truth is that the epidemiologist has been working together with the thoracic surgeon for two decades and Dr. Bernardino Clavo, head of the Research Unit of Dr. Negrín, who brings together extensive experience in ozone management. "The idea is that hospitals from different countries participate, although the main one will be the King Faisal Specialist Hospital & Research Center," adds Dr. Clavo. «In my case, I will be very involved in advising on the use of ozone in patients. I will do this based on the experience we have both in clinical trials and in compassionate treatments in circumstances in which there are no therapeutic options, "he continues, without forgetting to value the study carried out with rats.
But his work will go further, since he will also have to train the doctors who are going to use this gas and resolve any possible doubts that may arise. “Ozone is a molecule that is made up of three oxygen atoms, which is why it is much more reactive. However, if used properly, it is capable of generating stimuli in the body that try to adapt to the oxidative stress that it produces, manufacture antioxidant mechanisms and enhance anti-inflammatory mechanisms, ”highlights the expert, who hopes that the research work may be useful in offering a hopeful window to patients requiring lung transplantation.