The collaboration between the Sant Joan de Déu Research Institute (IRSJD - UB) and the company Gate2Brain will make it possible to apply a technology to cross the blood-brain barrier of the brain and deliver drugs there. An applied research that wants to carry out safe and transferable treatments for cases of childhood cancer, specifically those that are currently fatal or that leave irreversible sequelae.
When we talk about cancer, especially childhood or pediatric cancer, the general public is often not aware of the differences with cancer in adults. Not only because of the factors surrounding the treatment, but especially because of the causes that originate it. An adult with cancer can take care of the risk factors that have led him to one of the most feared diseases, according to the habits he has had, but this is not the case of a child . At the Hospital de Sant Joan de Déu they know this better than anyone, rightly so as they are one of the most important highly specialized pediatric centers in Europe and a reference in children's oncology; reason that justifies that more than three hundred children and adolescents are treated every year at the Hospital for all kinds of developmental cancer. The fact that the Sant Joan de Déu Hospital is one of the centers with the highest volume of pediatric oncology patients in Europe, and with the best survival rates, attracts many cases from all over the world that need guarantees of cure.
The good news, in general, is that the treatment of childhood cancer has improved greatly over the past twenty-five years, with overall cure rates rising from 20-30% in the late 1970s to at 75% currently ( Fernández-Delgado, 2016) . In the field of pediatric oncology, many advances have saved the lives of thousands of child patients, thanks in large part to understanding diseases from a genetic perspective and improving prognostication. This has undoubtedly been a turning point, but we need to go further. To take a step forward in therapeutic studies before applying them to the definitive clinic, studying in depth the impact of drugs on the body of children affected by cancer, researchers from the IRB Barcelona, the University of Barcelona (UB ) and the Sant Joan de Déu Research Institute – Sant Joan de Déu Hospital (SJD-UB) created the Gate2Brain spin-off in 2020, a finalist in the Catalan Pitch Competition 2021 . After fifteen years as a researcher at the Biomedical Research Institute (IRB) and co-directing ten doctoral theses, Dra. Meritxell Teixidó made the leap to the creation of Gate2Brain , of which she is the founder and is currently CEO. Just the name of the company already gives us a lot of information about the technology it develops: a door to the brain to overcome barriers, the brain, yes, but also the barriers in pediatric oncology to bring all the children of the world l 'hope and health.
If we put ourselves in the shoes of any family with a child with cancer, the worst-case scenario is that your child is diagnosed with a very uncommon type of childhood brain cancer, for which there is currently no treatment available. This is where the Industrial Doctorate project between Gate2Brain and Hospital Sant Joan de Déu launches collaborative research. The objective is to find a solution to the problem, and apply the results in the clinical field, seeking to save the lives of pediatric patients who today have no effective treatment . The technology to transport drugs to the brain is the innovation that Gate2Brain brings to biomedical research, and to understand it you need to know well how the brain works. This is how Teixidó, the company's CEO, explains: " the brain is, without a doubt, one of the most precious organs in our body and that is why it is very protected. We find this protection in the form of a blood-brain barrier that separates the blood from the brain parenchyma. The barrier is formed at the level of the cerebral capillaries that have tight junctions between the endothelial cells that make them up . But what happens to the nutrients that must enter the brain, and the waste that must leave it? This is where small proteins called peptides come into play. When one cell comes into contact with another, between cells of the same body or, for example, a white blood cell with a bacterium, the peptides act as a key and padlock. If there is a match there will be an exchange, if the key and padlock do not match the door will not open. Teixidó uses a metaphor that helps a lot to understand how this blood-brain barrier works: " we can imagine it like the wall of medieval cities, it has doors or transport mechanisms through which nutrients enter and waste leaves. Our keys use these doors without affecting their natural operation . This is how the technology used by Gate2Brain achieves that three families of peptides have the ability to cross the blood-brain barrier and transport drugs that cannot reach it without help. These three families correspond to the three patents that have been licensed by the company. The peptides used in this technology as keys are chemically prepared, inspired by peptides found in nature and with a great resistance that gives them great competitiveness.
"As part of the Industrial Doctorate we are exploring the use of these keys to improve the transport of a chemotherapeutic agent to fight against pediatric brain tumors that have an intact barrier and this makes treatment difficult"
Many researchers develop drugs every day for a large number of treatments for brain diseases, such as Alzheimer's or Parkinson's, but only 2% of these drugs can cross the brain's blood-brain barrier. Solving this problem is essential for the work being carried out at the Sant Joan de Déu Research Institute, where researcher Dr. Ángel Montero directs the research group on Pediatric Cancer Treatment , and supervises the work of industrial PhD student Clàudia Resa . One of the key objectives of this project is to be able to design and evaluate new therapeutic approaches to generate knowledge with clinical application . Specifying a little more, Teixidó explains that " within the framework of the Industrial Doctorate we are exploring the use of these Keys to improve the transport of a chemotherapeutic agent to fight against pediatric brain tumors that have an intact barrier and this in makes it difficult to cure ”. Moving forward towards the cure of these pediatric diseases requires intensive work in the preclinical field, which allows the generation of models derived from patients who, in Teixidó's words, " are a gift from the families " who have offered their children's tumors to contribute to research progress . Their importance lies in the fact that these models make it possible to ensure that the treatments studied by Montero's team are applicable to patients or are not functional . This is why these models have a high scientific value, and as Montero details: " we have distributed these models to more than 60 top-level international laboratories, and they have served to generate scientific information that has led to the design of several trials clinical phase 1 ".
The collaboration between the two project actors is key to applying the results of the shuttle peptide hypothesis, and developing safe and transferable treatments to the clinic for diseases that are currently fatal or leave irreversible sequelae. It is worth highlighting a fact that is even more relevant: if this research achieves its goal after the completion of the Industrial Doctorate, the impact can be very large in the clinical field of thousands of patients, and not only in the field of pediatric oncology . Advances in medicine save lives, but in order to make progress in this regard, laboratories or hospitals must work in collaboration with other areas. Cooperation in this context is essential to obtain impactful results, in the words of Montero: " this project is a clear example of collaboration between a health research center and a company intent on making its technology available as soon as possible to the patients ". Industrial Doctorate projects like this allow collaboration between the more academic field of health with entrepreneurs and companies whose purpose is to reach the clinical application of their ideas.
"This project is a clear example of collaboration between a health research center and a company intent on bringing its technology to patients as quickly as possible"
The project team's research makes it possible to create a two-way knowledge bridge with the day-to-day life of the hospital, a reality that "allows projects to move forward exponentially", remarks Teixidó. According to Montero: " the only way to transfer knowledge and innovation to patients is through clinical trials that evaluate our proposals independently and without bias ". On the other hand, different independent experts in science, medicine and ethics apply very strict filters so that a clinical trial proposal is approved, and finally a new drug can be used in a treatment. All together with a clear horizon: design and execute a regulatory plan to reach the first clinical trial patient in three years . A project that must be, in Montero's words, " robust, original, with solid intellectual property, validated in excellent experimental models, and published in the best international sources ".
After all, we are talking about applied research, where the result of the doctoral student's work must have an impact on patients who currently do not have a treatment available. An impact that will undoubtedly bring hope and excitement when the results of the project can be transferred to a future clinical trial; it also means that Clàudia benefits from the impact of working in a highly multidisciplinary dual environment . On the other hand, this kind of applied research projects also serve to train the talent of young people like Clàudia, one of the academic purposes of Dr. Àngel Montero, helping them start their scientific and technical career in a dual field: academic and business. The opportunity to participate in an R+D+I project of these characteristics generates a high added value to Clàudia's curriculum, who came to the Montero team to be able to do the final degree project and the Master's thesis. During the drafting of the TFM is when Clàudia considered whether she wanted to continue in the field of research, and then she received the proposal to participate in the project and become the knowledge transfer bridge between the Hospital and the company Gate2Brain. The future PhD student was so clear: " I didn't have to think much about the answer. On the one hand, I knew the excellent level of the research group, and, on the other, the translational goals of the project. I saw it as a unique opportunity to train and do my part to develop and apply new therapeutic strategies against childhood cancer ." The process of training this talent is a shared purpose from the Generalitat's DI Plan, which additionally offers doctoral students training in transversal skills that are very attractive for the business world. One of the aspects that Clàudia most highlights from her experience in this type of doctorate is the double vision, academic and business, of the process of developing new therapeutic strategies . Her company tutor highlights Clàudia's learning path in this project, oriented towards a successful professional future: " knowing that there is more beyond basic research, and how this is being developed until it is a product on the market ," Teixidó emphasizes.
In short, projects like this are a good example of how applied and collaborative research can contribute to the competitiveness and internationalization of the Catalan industrial fabric; they allow companies to attract talent with high added-value knowledge and skills, while the more academic realm can transfer its technology and knowledge to the productive environment. As Teixidó explains: " Industrial Doctorates are a model of benefit and growth for both sides, without a doubt a path of growth and reciprocal knowledge between very different environments ". The results of this project can change the lives of thousands of families, providing hope and solutions for their children.
