Blockade of a clotting protein during stroke process reduces brain damage in experimental models

Researchers at the Cima University of Navarra confirm for the first time that FXIII increases clot density and resistance to current treatments in thrombi of stroke patients

Lara Montori, Juan Marta, José Antonio Rodríguez, Josune Orbe, Florencio Machado and Miriam Belzunce, from Cima University of Navarra

March 26, 2024

Researchers at the Cima University of Navarra have shown that blocking a coagulation protein during the process of stroke development reduces brain damage in experimental models.

Stroke is the second leading cause of death in our environment (first in women) as well as the leading cause of acquired disability in adults. The costs derived from stroke account for around 3-4% of the total health expenditure in our country, in addition to an important personal and family social burden, with a great impact on the person who suffers it and their caregivers.

Ischemic stroke is the most common (85%) and is mainly caused when a thrombus obstructs the cerebral arteries, preventing them from being properly supplied with blood. The treatment of stroke consists of the administration of a thrombolytic, tPA, which acts by dissolving the thrombus to save part of the brain tissue at risk of dying. However, it should be administered in the first hours after stroke, its efficacy is poor in the case of large vessel occlusions and it is contraindicated in those patients with a higher risk of developing hemorrhagic complications.

Coagulation factor XIII is known to be involved in the formation of thrombi that cause ischemic stroke. In addition, it has been shown to be involved in other processes, such as tissue remodeling and protein binding, which may be involved in resistance to current stroke treatments. "The novelty of our work is that we have managed to administer for the first time a molecule capable of blocking FXIII while stroke is occurring in experimental models," says Dr. Juan Marta, first author of the study. 

Moreover, as Dr. Josune Orbe, researcher at the Cima University of Navarra and director of the study, points out, "we have shown that it reduces brain damage and improves the functional state of the mice". The conclusions have been published in the scientific journal Journal of Thrombosis and Haemostasis.

Combination with current treatment

The work confirms that the presence of factor XIII is associated with increased clot stiffness, increased density of fibrin fibers (a major protein of blood clots) and increased binding of alpha2-antiplasmin protein, leading to resistance to lysis or "dissolution" of the thrombus. "In this line, lysis experiments of thrombi obtained from stroke patients show greater efficacy of tPA treatment when it is combined with the FXIII inhibitor molecule" says the Cima researcher. 

This study opens up a new pathway for the treatment of ischemic stroke by combining an FXIII inhibitor with the standard of care treatment in order to enhance its effect. As Dr. Orbe explains, "these are preclinical results, so further studies are needed before clinical trials can be considered".  

This study was carried out thanks to the collaboration of patients who donated their samples to the biobanks of the University of Navarra and the Aragon Health System. It has been carried out within the framework of the Cooperative Research Networks Oriented to Health Outcomes (RICORS)-Ictus and CIBER Cardiovascular (CIBERCV), with the collaboration of the Clínica Universidad de Navarra, Hospital Universitario de Navarra, Hospital Universitario Vall d'Hebron and Hospital Universitario Miguel Servet.