CERECAP Update
Several years ago, EVER Pharma started a comprehensive project with the aim to detect clinically beneficial effects of Cerebrolysin® in ischemic stroke when used in combination with recanalization strategies such as thrombolysis, thrombectomy or both.
The timing of this clinical development strategy comes at the right moment: Globally recanalization rates are improving but a high rate of futile recanalization and, consequently, poor long-term clinical outcome remains a problem.
This unresolved problem also led to an intensified discussion regarding the potential of neuroprotective agents on promoting recovery and minimizing injuries since recanalization strategies increase the chance that neuroprotective substances reach the tissue-at-risk (the penumbra).
Another important issue in this context is whether Cerebrolysin®offers a treatment strategy for one of the most serious complications of revascularization: hemorrhagic transformation. This occurs in 10–40% of patients with ischemic stroke undergoing thrombolytic or endovascular therapy and contributes to the increase in stroke morbidity and mortality.
First preclinical and clinical results are very promising.
- A preclinical study at Michael Chopp’s Department of Neurology at the Neuroscience Institute at Henry Ford Hospital in Detroit investigated the well-known inflammatory effects of rt-PA and fibrin which result in reduced levels of Blood Brain Barrier(BBB) proteins such as claudin and occludin. Michael Chopp and his team found that the levels of these proteins were significantly ameliorated by the administration of Cerebrolysin®, resulting in a normalization of these proteins and, consequently, improvement of the BBB integrity.
- The clinical pilot study, Poljakovic et al. 2021 showed already with a small number of patients very promising results. The overall rate of hemorrhagic complications was significantly reduced and there was a clear trend for a favorable outcome at month 12 in Cerebrolysin® treated patients.
- The methodology paper by Staszewski et al. 2022 presents a study that is designed to determine the efficacy of Cerebrolysin® as an add-on therapy to mechanical thrombectomy in reducing global disability in patients with acute ischemic stroke. The trial uses a more comprehensive treatment strategy over 21 days with a 30ml dosage and a 2nd treatment cycle with Cerebrolysin®. In this study, special attention is paid to include suitable patients with good collateral circulation in order to increase the likelihood that Cerebrolysin®, when administered within eight hours after the onset of stroke, will reach the penumbra and protect endangered tissue.
- Another study currently enrolling patients at the Pomeranian Medical University, University Hospital no.1 Szczecin, Poland, assessing Early Administration of Cerebrolysin® on the Outcome of Patients With Acute Stroke Undergoing EVT has similar objectives.
- A study in Bangkok, Thailand, assesses safety and feasibility of an early treatment start with Cerebrolysin® in a pre-hospital setting: in ambulances and mobile stroke units. This study includes also hemorrhagic stroke patients.
Altogether, 12 pilot-studies are ongoing with interesting focus on e.g. diabetic patients (known for being especially at risk for hemorrhagic transformation due to a more brittle BBB), cardioembolic stroke (an etiology known for a higher bleeding risk), or wake-up stroke (with unknown onset of stroke).
EVER Pharma hopes to offer more comprehensive treatment options, from early treatment with Cerebrolysin® in pre-hospital settings to the combination of the gold-standard endovascular therapies and Cerebrolysin® as add-on therapy.
The objective in all these studies is to achieve a reduction in global disability and a prevention of hemorrhagic complications by improving the BBB integrity.