i3S research receives €3 million from the «la Caixa» Foundation
Projects in the areas of brain damage, glioblastoma treatment and autism spectrum disorder were recognised in the 2025 ”la Caixa” Foundation Health Research competition.
Developing new therapies for neurological diseases such as stroke, epilepsy and amyotrophic lateral sclerosis, creating an implantable device to treat glioblastoma and improving the assessment of the risk of developing autism are the main objectives of the three projects led by researchers from the Institute for Research and Innovation in Health at the University of Porto (i3S), which have just been recognised in the ”la Caixa” Foundation's Health Research competition. The total funding amounts to almost three million euros.
The three proposals from i3S are among a total of 34 Portuguese and Spanish biomedical research projects of excellence, which will receive more than €26 million. In this eighth edition, 714 basic, clinical and translational research proposals were submitted, with nine Portuguese and 25 Spanish proposals being selected. Under this competition, the “la Caixa” Foundation awards up to €500,000 to projects involving a single research institution and up to €1 million to research consortia formed by several institutions, as is the case with projects led by i3S researchers.
A new way to combat brain damage from within
Led by Ana Paula Pêgo, head of the NanoBiomaterials for Targeted Therapies group, the MIND project was funded by the “la Caixa” Foundation and the FCT with one million euros and will focus on neurological diseases such as stroke, epilepsy and amyotrophic lateral sclerosis (ALS), which affect millions of people worldwide, often causing long-term disability or even death.
One of the main causes of brain damage associated with these diseases, explains the i3S researcher, " is the buildup of a chemical in the brain that, in excess, can lead to neuronal cell death. Despite years of research, no treatment has successfully protected the brain from this process." Although most studies have focused on neuroprotection strategies targeting neurons, Ana Paula Pêgo believes that the key may lie in a different type of brain cell: astrocytes.
This project proposes a new brain protection strategy, which consists of enhancing the efficiency of astrocytes. As the researcher explains, “astrocytes remove excess harmful chemicals, but during a stroke or another acute neurological event, they cannot maintain balance, leading to the accumulation of damage.” As such, the team proposes an innovative solution: “Directly introducing useful instructions into astrocytes through messenger RNA (mRNA), which tells the cells to produce larger amounts of a key protein that eliminates the harmful chemical.” To ensure the safety and efficacy of the treatment, the researchers are developing small smart particles capable of releasing their cargo only in the damaged areas of the brain.
The project, which will be developed in consortium with researchers Francisco Campos, from the Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS) (Spain), and Ben Maoz, from Tel Aviv University (Israel), also includes the development of a relevant three-dimensional (3D) model to mimic the human brain, which “will allow testing the therapy under realistic physiological conditions, as well as the use of advanced imaging tools to monitor the effects of the treatment, which will be tested in the context of stroke,” emphasises Ana Paula Pêgo.
If the proposed objectives are achieved, the scientist assures us, “this approach could pave the way for new therapies, not only for stroke but also for other brain diseases with similar mechanisms of neuronal damage.”
Implantable device for administering drugs against glioblastoma
Funded with €990,000, the project led by Bruno Sarmento, in partnership with researchers Bruno Costa, from the University of Minho, and Álvaro Mata, from the University of Nottingham (United Kingdom), will focus on the treatment of glioblastoma, the most lethal type of brain cancer in adults. Current treatments, which include surgery, radiotherapy and chemotherapy and have evolved little over the last two decades, have limited results due to tumour resistance and the difficulty of delivering drugs directly to the brain.
The team aims to revolutionise the treatment of glioblastoma by developing an implantable therapeutic system capable of releasing anti-cancer molecules directly into the brain after tumour removal surgery. The system, explains Bruno Sarmento, “is designed to release, in a controlled and gradual manner, a combination of drugs that fight cancer more effectively and reduce the need for daily chemotherapy.”
The project, he adds, “involves the design of a new type of implant capable of releasing chemotherapy drugs, treatment resistance inhibitors, and RNA sequences specifically targeted at cancer cells.” The goal, Bruno Sarmento emphasises, is for “this innovative strategy to improve the effectiveness of drugs, reduce side effects and increase patient survival and quality of life.”
The preliminary data, says the leader of the Nanomedicines & Translational Drug Delivery group, are promising: "The new system has been shown to significantly reduce tumour growth in laboratory models. The expected results include higher survival rates, fewer adverse effects and a new standard of care for patients with glioblastoma.” These advances, he adds, “could also pave the way for the development of similar treatments for other types of brain tumours, with a significant impact on public health and healthcare costs."
How small changes in DNA shape the developing brain
It is known that autism spectrum disorder (ASD), which affects approximately one in every 44 children, has a strong genetic basis. However, most of the genes linked to ASD are not found in the genes themselves, but in the non-coding regions of DNA that control how genes are turned on and off. The team led by i3S researcher Diogo Castro wants to understand how these changes influence brain development with the aim of “explaining why ASD occurs and improving how we assess the risk of developing this disorder.”
This project, funded by the “la Caixa” Foundation in collaboration with FCT, with more than €730,000, aims to uncover how these non-coding genetic changes affect brain development, particularly in the early stages when the brain’s structure is being formed.
The consortium teams, which include researchers Gaia Novarino from the Institute of Science and Technology Austria (ISTA) (Austria) and Justin O'Sullivan from The Liggins Institute, University of Auckland (New Zealand), will use advanced tools to test thousands of genetic variants to see how they influence gene activity in human brain cells grown in the lab.
In addition, Diogo Castro explains, “we will use machine learning to identify which of the genetic changes linked to ASD have the most predictive value, creating a model that could help predict who is at risk, thus allowing an early diagnosis and interventions.”
To understand how these changes affect brain development, the project's researchers, according to the i3S researcher, “will edit specific genetic variants into stem cells and grow them into mini-brains, or organoids. This will allow them to observe how these changes impact the formation and function of brain tissue”. The project brings together experts in brain development, genetics, and data science, making it well-positioned to tackle this complex challenge.
About the 2025 ”la Caixa” Foundation Health Research Competition
The awards ceremony took place on 20 November at the CosmoCaixa Science Museum. According to Àngel Font, Deputy Director General of Research and Grants at the ”la Caixa” Foundation, “biomedical research is one of the most powerful ways to improve people's lives. The 34 winning projects address very diverse challenges from different perspectives, but they all share three fundamental pillars for moving towards a more promising future for patients and their families: collaboration, talent and innovation.‘ According to the ’la Caixa" Foundation, this year's Portuguese projects stand out for their innovative nature and high social impact.
This year, the La Caixa Foundation has entered into agreements with the Breakthrough T1D Foundation and the Luzón Foundation, which have allowed it to place greater emphasis on funding initiatives focused on type 1 diabetes, with two projects funded, and amyotrophic lateral sclerosis (ALS), with one project funded. The competition also has the collaboration of the Foundation for Science and Technology (FCT), which allocated €1.8 million to fund three of the nine Portuguese projects awarded in this edition.
Since the programme began in 2018, the total amount of the ”la Caixa” Foundation's Health Research competition has reached €172.3 million for 234 projects, of which 162 are led by Spanish teams and 72 by Portuguese research groups.