New funding for acute stroke research

January 2020

The Cellular and Molecular Neurobiology Group led by Dr Teresa Gasull has been awarded funding to research acute stroke.  The project Apotransferrin, a new treatment for acute stroke has been awarded funding by the Agency for Management of University and Research Grants (AGAUR) with the support of the European Union within the programme Ajuts Producte destinats a l'obtenció de prototipus i a la valorització i transferència dels resultats d'investigació generada per equips de recerca de Catalunya.

The project is led by Dr Gasull, with the participation of Marc Melià.

Stroke is a medical emergency which results from a sudden disruption in blood flow to the brain, caused either by clot/thrombus obstruction of one artery (ischemic stroke) or by bleeding from an intracranial blood vessel (haemorrhagic stroke). Fifteen million people in the world suffer their first stroke each year (17 million including recurrent stroke), but the best acutely provided treatments only help fewer than 15% of these people to improve (still one third of patients die and one third remain disabled). The successful treatment of stroke is, thus, an unmet medical need. The majority (80-85%) of all strokes are ischemic (AIS) and the remaining 15-20% of the haemorrhagic subtype (ICH). To date, the only acute therapeutic strategy found effective in these patients is re-establishing the blood flow as soon as possible in the AIS type, either using the thrombolytic molecule tissue plasminogen activator (tPA) or, when tPA is not working, using mechanical removal of thrombus by endovascular thrombectomy (EVT) in a high-tech costly operating room procedure.

In stroke patients judged severe at enrolment, when carefully selected using MRI imaging, EVT can provide functional independence following successful recanalization. Despite these recent EVT advances, half EVT-treated AIS victims exhibit deterioration of functional status not being functionally independent at 90 days assessed.

The mechanisms of this deterioration after successful EVT include excessive oxidative stress and reperfusion injury, neuronal excitotoxicity and vascular injury. Neuroprotectants target these mechanisms, providing a further rationale for their use in this new scenario in which reintroduction of blood supply by EVT provides a freeway fo oxygen, nutrients and, importantly, for the treatment drug to access the brain area at risk. Thus, neuroprotective agents should be considered in proof-of-concept studies to be used as an adjunvant therapy together with state-of-the-art EVT. We propose apotransferrin (ATf) as a powerful neuroprotector that we already have tested in ischemic stroke models using EVT-like procedures; it acts in a mechanisms that when targeted in AIS patients results in better outcomes. We aim to provide proof-of-concept efficacy in patients.

Funding

This project is funded by the Agency for Management of University and Research Grants (AGAUR) and cofinanced by the European Regional Development Fund (ERDF) of the European Union (project number: 2019PROD001202) with 99.795,0 €.