The collaboration between the Sant Joan de Déu Research Institute (IRSJD - UB) and the company Gate2Brain will allow the application of a technology to cross the blood-brain barrier of the brain and deliver drugs to it. This applied research aims 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 pay attention to the risk factors that have led them to one of the most feared diseases, depending on the habits they have had, but this is not the case for a child . At the Hospital de Sant Joan de Déu they know this better than anyone, rightly they are one of the most important highly specialized pediatric centers in Europe and a reference in pediatric oncology; a reason that justifies that more than three hundred children and adolescents are treated every year at the Hospital for all types of developmental cancer. The fact that the Hospital de Sant Joan de Déu 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 in the last twenty-five years, with an increase in overall cure rates that have gone from 20-30% in the late seventies, to 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 prognostic capacity. 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 IRB Barcelona, the University of Barcelona (UB) and the Institut de Recerca Sant Joan de Déu – Hospital Sant Joan de Déu (SJD-UB) created the spin-off Gate2Brain in 2020, a finalist in the Catalan Pitch Competition 2021. After fifteen years as a researcher at the Institute for Biomedical Research (IRB) and co-directing ten doctoral theses, Dr. Meritxell Teixidó made the leap to create Gate2Brain , of which she is the founder and, currently, CEO. The name of the company alone gives us a lot of information about the technology it develops: a door to the brain to overcome barriers, that of the brain, yes, but also the barriers within pediatric oncology to bring hope and health to all the children of the world.
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, which currently has no treatment. This is where the Industrial Doctorate project between Gate2Brain and the Hospital Sant Joan de Déu launches collaborative research. The aim 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 currently 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 how the brain works. This is how Teixidó, CEO of the company, 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 the blood-brain barrier that separates the blood from the brain parenchyma. The barrier is formed at the level of the brain capillaries that have tight junctions between the endothelial cells that form them ”. 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 in 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 as the wall of medieval cities, with doors or transport mechanisms through which nutrients enter and waste leaves. Our keys use these doors without affecting their natural functioning ”. 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 that we find in nature and with great resistance that gives them great competitiveness.
"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 pediatric brain tumors that have an intact barrier and this makes it difficult to cure"
Every day, many researchers develop drugs 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 blood-brain barrier of the brain. Resolving this problem is crucial for the work carried out at the Sant Joan de Déu Research Institute, where researcher Dr. Ángel Montero leads the research group on Pediatric Cancer Treatment , and supervises the work of industrial doctoral 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 . To be more specific, 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 makes their treatment difficult ." Moving towards the cure of these pediatric diseases requires intense work in the preclinical field, which allows the generation of models derived from patients who, in the words of Teixidó, “ are a gift from the families ” who have offered their children's tumors to contribute to the progress of research . Their importance lies in the fact that these models allow us to provide certainty 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 first-level international laboratories, and they have been used to generate scientific information that has led to the design of several phase 1 clinical trials .”
The collaboration between the two actors of the project 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 that leave irreversible sequelae. It is worth highlighting an even more relevant fact: if this research achieves its objective once the Industrial Doctorate is completed, the impact could be very great 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 progress in this sense, laboratories or hospitals must work in collaboration with other areas. Cooperation in this context is essential to obtain results with impact, in the words of Montero: “ this project is a clear example of collaboration between a health research center and a company determined to get its technology to patients as soon as possible ”. Industrial Doctorate projects like this allow collaboration between the more academic field of health with entrepreneurs and companies whose aim is to achieve the clinical application of their ideas.
“This project is a clear example of collaboration between a health research center and a company determined to get its technology to patients as soon as possible”
The research of the project team allows the creation of a two-way knowledge gateway with the day-to-day life of the hospital, a reality “that allows projects to advance exponentially”, highlights Teixidó. According to Montero: “ the only way to transfer knowledge and innovation to patients is through clinical trials that evaluate our proposals in an independent and unbiased way ”. 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 with a clear horizon: to design and execute a regulatory plan to reach the first patient of the clinical trial in three years . A project that must be, in the words of Montero “ 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 is also worth noting that Clàudia benefits from the impact of working in a highly multidisciplinary dual environment . On the other hand, this type of applied research projects also serve to train the talent of young people like Clàudia, one of Dr. Àngel Montero's academic purposes, helping them to 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 high added value to Clàudia's curriculum, who came to Montero's team to be able to do her final degree and master's thesis. While writing the TFM, 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 doctoral student was so clear about it: “ I didn't have to think about the answer much. On the one hand, I knew the excellent level of the research group, and, on the other, the translational objectives of the project. I saw it as a unique opportunity to train myself and do my bit 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, on the process of developing new therapeutic strategies . Her business tutor highlights Clàudia's learning path in this project, oriented towards a successful professional future: " knowing what lies beyond basic research, and how it progresses to becoming a product on the market, " highlights Teixidó.
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 knowledge and skills of high added value, while the more academic field 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.
