ICVS researchers Agostinho Carvalho and Patrícia Maciel won the CaixaResearch Health 2024 award, a competition run by the “la Caixa” Foundation.
Agostinho Carvalho’s project secured funding of around one million euros that will allow him to explore how genetic factors influence the risk of infection in immunosuppressed patients to improve the disease prediction and its treatments. Every year, more than two million people are infected by the fungus Aspergillus, with up to 60 to 80% of the cases resulting in death due to resistance to current antifungal treatments. Machado-Joseph disease is a rare inherited neurodegenerative disorder with no effective treatment yet. With funding of around one million euros secured by Patrícia Maciel’s project, her team will develop molecules that can eliminate the mutated proteins that cause this disorder in nerve cells.
In collaboration with Vinod Kumar (Radboud University Medical Center, Netherlands) and Coral Barbas (Centre of Metabolomics and Bioanalysis, Spain), Agostinho Carvalho’s project entitled “A High-Resolution Functional Genomics Approach to Inform Precision Medicine for Fungal Disease” aims to identify the genetic variations that control immunity to the Aspergillus fungus and the molecular mechanisms that predispose to the disease in immunosuppressed patients. This will open the door to identifying new biomarkers to predict the risk of infection, as well as potential therapeutic targets for personalized treatments. Aspergillosis is an infection caused by the fungus Aspergillus, which is present everywhere in the air we breathe, both outdoors and indoors. Most people inhale Aspergillus spores every day without becoming infected, but those with pre-existing conditions or triggered immune systems are at risk. This affects the respiratory system; Severe infection can lead to pneumonia and may spread to other parts of the body, being associated with high levels of mortality due to the severity of its clinical manifestations and resistance to current antifungal treatments. It is estimated that more than 2 million people worldwide contract the infection each year, and that 60-80% of these patients die from it annually.
For Agostinho Carvalho “this financing is important because it will allow us to maintain some cohorts that we have used to identify diagnostic and therapeutic targets for these infections” and “to add to this consortium collaborators with differentiated expertise in some methodologies, creating a multidisciplinary approach that allows us to identify these new diagnostic and therapeutic targets that we intend to implement.” The ICVS researcher also says that “the recognition from the la Caixa foundation is extremely important for us, a recognition of the quality of research we develop”.
“New molecules harnessing targeted protein degradation for the treatment of Machado-Joseph disease” is the project title of the work developed by Patrícia Maciel, in collaboration with Fernanda Borges (CIQUP, Portugal). Machado-Joseph disease is a rare inherited neurodegenerative disorder that affects one or two cases per 100,000 population and primarily causes symptoms such as poor coordination of movements, unsteady gait (ataxia), weakness in arms and legs and difficulty with speech and swallowing. It is caused by mutation of a protein called ataxin-3, which tends to aggregate, leading to toxic effects on neurons and resulting in their progressive dysfunction and disappearance. In addition to gene therapies aimed at silencing the expression of the mutant gene, which are currently being tested and face several major challenges related to safety and effective delivery of the therapy to the affected regions of the brain, other therapies are being explored based on the administration of small molecules capable of inducing protein degradation. In this regard, Patrícia Maciel’s project will work with small bifunctional molecules that bind to both the mutated protein and the cellular machine responsible for protein degradation and elimination. The goal is to develop these small molecules as a promising alternative to gene therapy to selectively eliminate the mutated proteins that cause this disorder in nerve cells.
For ICVS researcher Patrícia Maciel “the financing from the “la Caixa” Foundation will allow us to carry out a set of activities that would not be possible with less funding…it will allow us to make a qualitative leap in terms of research”. Patrícia Maciel also states that “it was a great joy to have the recognition of an idea that I had been seeking to develop for a long time”.
The “la Caixa” Foundation selected 29 biomedical research projects of excellence and with high social impact within the scope of the CaixaResearch Call for Health Research 2024, endowed with 25.7 million euros to be carried out in research centers, hospitals and universities from Spain and Portugal, with the contribution of the Foundation for Science and Technology (FCT), which finances 3 of the 9 Portuguese projects selected in this edition with 2.9 million euros.
