09/01/2025 - Press release
A study involving more than 400 patients who suffered an ischemic stroke, led by a team from the Hospital del Mar Research Institute, has identified a link between poorer patient outcomes and high blood levels of five microRNAs, RNA particles that modulate the activation and deactivation of specific genes. The research, conducted in collaboration with Hospital del Mar, the University Hospital Complex of Albacete, the Arnau de Vilanova Hospital in Lleida, and the Son Espases Hospital in Mallorca, has been published in Neurology. This is the first large multicenter study in Europe to analyze this relationship.
Researchers examined over 2.000 circulating microRNAs in blood samples. In an initial phase, samples from 215 individuals who suffered an ischemic stroke and were treated at Hospital del Mar between 2009 and 2018 were analyzed. They identified a set of microRNAs that appeared to be elevated in patients with poorer outcomes three months post-stroke, after adjusting for other variables such as age, sex, and initial stroke severity. These results were subsequently validated in a second cohort of 191 patients from different centers, where the 26 most significant microRNAs were analyzed. The findings clearly reproduced the association of five of these molecules with patient prognosis.
"The main implication of our study is that these microRNAs may represent potential therapeutic targets, as they regulate genes involved in processes such as neurogenesis and angiogenesis," explains Dr. Jordi Jiménez Conde, coordinator of the Neurovascular Research Group at the Hospital del Mar Research Institute and attending physician in the Neurology Department. "There are mechanisms associated with these particles that are particularly interesting due to their involvement in processes that can aid the recovery of stroke patients, such as neuron regeneration and the formation of related structures, as well as blood vessel regeneration," adds Dr. Jiménez Conde. Importantly, these molecules regulate approximately 60% of human protein-producing genes.
Potential Treatment to Improve Prognosis
The study highlights that these molecules can serve as reliable prognostic markers in combination with other risk factors, facilitating more careful monitoring during the recovery phase. Measuring their levels can be done through a simple blood sample.
Some of the identified microRNAs already have inhibitors that can modulate their activity on the genes they regulate. This opens the door to studying pathways that leverage their function as potential treatments to improve the prognosis of ischemic stroke patients. "Now, we need to study their functions, analyze how they can be modulated through experiments with in vitro neurons and in vivo mice models. If this works, we could develop potential tools to alter patient outcomes by interacting with the pathways they influence," notes Isabel Fernández Pérez, a predoctoral researcher at the Hospital del Mar Research Institute and attending neurologist.
That said, this is still a field with some uncertainties. "A microRNA can act on multiple genes simultaneously, which can be positive but also complicates its study. We have already observed the association with prognosis, and now we will work to confirm the causal relationship and the possibility of using them as treatments," explains Dr. Fernández Pérez.
Ischemic stroke is the leading cause of disability in adults and the second leading cause of death globally, according to the World Health Organization. Each year, approximately 13 million people suffer a stroke, and five million are left with long-term disability. However, these outcomes vary greatly among individuals, regardless of clinical factors or stroke severity. Genetic and epigenetic factors, like those identified in this study, can help explain this variability in outcomes among different individuals.
This study was partially funded by the Carlos III Health Institute and the European Regional Development Fund (ERDF), through RICORS-ICTUS, RD21/0006/0021, the MARIAS project (PI18/00022), and the Sara Borrell program CD22/00001 (J.J.-B.).
Reference Article
Fernández-Pérez I, Vallverdú-Prats M, Rey-Álvarez L, Giralt Steinhauer E, Ois A, Cuadrado-Godia E, Rodriguez-Campello A, Suárez-Pérez A, Macias-Gómez A, Soriano-Tárraga C, Purroy FF, Arque G, Tur S, Cañellas G, Vives-Bauza C, Segura T, Serrano-Heras G, Lazcano U, Jiménez-Balado J, Jiménez-Conde J. Circulating miRNAs Associated With 3-Month Outcome in Patients With Acute Ischemic Stroke. Neurology. 2025 Jan 14;104(1):e210085. doi: https://www.neurology.org/doi/10.1212/WNL.0000000000210085. Epub 2024 Dec 9. PMID: 39652811.
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