A cerebrovascular accident or stroke is a medical emergency because it interrupts the blood supply to the brain and early attention to restore it is crucial to save the patient’s life and prevent complications and sequelae. Every year 650,000 people die from this disease in Europe, 40,000 of them in Spain and, in addition to a very high mortality rate that makes it the first cause of death in women in our country and the third in men, it can cause irreversible disability. and dementia (it is the second cause of dementia after Alzheimer’s).
Now, the results of a study on ischemic stroke that began 15 years ago and has been led by the Hospital 12 de Octubre Research Institute i+12 and the Complutense University of Madrid (Drs. Ignacio Lizasoain and MA Moro) have shown that treatment with the drug ApTOLL reduces mortality in patients from 18% to 5%, and also decreases the chances of developing a disability.
ApTOLL is an aptamer, a nucleic acid (DNA/RNA) molecule capable of recognizing and binding to its therapeutic target with high specificity. In this case, it blocks the Toll-like receptor 4 (TLR4) innate immunity receptor, which is key in the activation of the inflammatory response. “Not only will it represent a new approach for the treatment of the acute phase of stroke and the prevention of its serious complications such as hemorrhagic transformation, but it could also be used in other diseases such as acute myocardial infarction or multiple sclerosis, in which that the TLR4 receptor is involved”, has declared Lizasoain.
“ApTOLL at a dose of 0.2 mg/kg within 6 hours of stroke onset in combination with endovascular treatment is associated with a 18% to 5% reduction in mortality and 90-day disability”
The findings have been published in the scientific journal JAMA Neurology and are the conclusions of a clinical trial in which 150 patients with ischemic stroke have been evaluated. 15 hospital centers in Spain and France have participated in the study, including Hospital 12 de Octubre in Madrid, between 2020 and 2022, coordinated by Hospital Vall d’Hebron in Barcelona (Dr. M Ribó) and aptaTargets (Dr. M Hernández) and was presented this year at the International Stroke Conference in Dallas.
ApTOLL should be administered within the first 6 hours after stroke
“In 2007 we demonstrated the involvement of TLR4 in experimental stroke. ApTOLL is a drug born in the academic field that, after more than 15 years, reaches the clinical phase with spectacular results and breaking, for the first time, with a failed history of cerebroprotective drugs”, highlighted Lizasoain, professor of the Department of Pharmacology and Toxicology from the Faculty of Medicine of the UCM, researcher at Hospital 12 de Octubre and one of the architects of the development.
“The use of ApTOLL at a dose of 0.2 mg/kg within 6 hours of stroke onset in combination with endovascular treatment is shown to be safe and associated with a 18% to 5% reduction in mortality and disability at 90 days”, indicates Lizasoain. In addition, the administration of the drug has shown a reduction in the final volume of the infarct and in the severity of the stroke measured by the NIHSS scale 72 hours after the stroke.
The origin of ApTOLL is in the academic field, thanks to the initial funding received from the State Plan of the Ministry of Science and Innovation and the Carlos III Health Institute. In addition to the UCM and i+12, the Ramón y Cajal Institute for Health Research (IRYCIS; Dr. V González) and two companies, the biopharmaceutical and aptaTargets SL and the biotech Aptus Biotech, are participating in the research.
Regulatory preclinical studies and Phase I clinical safety trials with healthy volunteers were conducted in 2017. The drug is internationally patented with the participation of the Complutense University of Madrid (patent number CT/EP2015/064277) and in 2018 preclinical studies demonstrated that ApTOLL was not only effective as a brain protector in experimental models of stroke, but also its excellent profile of safety and toxicity allowed the clinical phase studies whose results have just been published to be carried out. In 2022 and led by the Hospital Universitario de la Princesa (Dr. F Abad-Santos), its safety and pharmacokinetics were evaluated in 46 healthy adult male volunteers.
Source: University Hospital October 12
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