Abu Dhabi, UAE — Cerebrolysin, a porcine-derived collection of growth factors already employed for a broad array of neurodegenerative disorders in Asia and Eastern Europe, was effective for stroke-related aphasia, the results of a double-blind, randomized controlled trial showed.

The study demonstrated that the drug, when used alongside speech therapy, led to greater improvements in stroke-related aphasia than speech therapy alone.

“If confirmed in larger studies, the combination of cerebrolysin and speech therapy could set a new standard in poststroke aphasia management,” said study investigator Dafin F. Muresanu, MD, PhD, Chairman, Department of Clinical Neurosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania.

He presented the study findings on October 24 at the 16th World Stroke Congress (WSC) 2024.

Studied for More Than 25 Years

Extracted from pig brain, one of the main constituents of cerebrolysin is brain-derived neurotrophic factor. Other peptides, such as glial cell line–derived neurotrophic factor, nerve growth factor, and ciliary neurotrophic factor, may also contribute to the neuroprotective and neuroregenerative effects observed in experimental work.

Clinical studies date back to at least 1998 and include clinical benefits observed in stroke, dementia, traumatic brain injury, and spinal cord injury. Although the degree of benefits has been mixed, including some trials that failed to show any significant benefit, many of the positive studies have been randomized and double-blind.

The European Cooperative Acute Stroke Study (ECASS) included 132 patients with non-fluent (Broca) aphasia who were enrolled within 3-5 days of the causative stroke. In this placebo-controlled, double-blind study, patients were randomly assigned in a 1:1 ratio.

In the experimental arm, patients received 30 mL/d cerebrolysin administered by intravenous (IV) infusion with a 0.9% saline solution. The placebo was an indistinguishable IV 250 mL 0.9% saline solution. The assigned therapies were administered at intervals for a total of 30 days over the 3-month period of the study. During this period, all patients in both groups received 1 hour of speech therapy per day.

The primary outcome was an improvement in language function as assessed by the Western Aphasia Battery (WAB). This was performed at days 0, 30, 60, and 90. The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) scores were secondary outcomes assessed at the same intervals.

Prior stroke, preexisting neurodegenerative or psychiatric diseases, and severe liver or renal failure were among the exclusion criteria.

Primary Endpoint Met at 30 Days

For the primary outcome, the advantage of cerebrolysin over speech therapy alone was already significant at 30 days (P < .001), and this relative advantage increased incrementally at 60 and 90 days. At the 90-day visit, the increase from baseline in WAB exceeded 35 points in the experimental arm but climbed only about 20 points (P < .001) in the control arm.

Muresanu characterized the treatment effect as “medium” at the 30-day follow-up but “large” at both the 60- and 90-day timepoints. The follow-up from ECASS, which was called a pilot study, does not yet extend past 90 days.

For the secondary endpoints, cerebrolysin had an insignificant advantage over speech therapy alone at 30 days for the NIHSS score, but the relative advantage increased over time, reaching significance at both day 60 (P < .01) and day 90 (P < .001).

Cerebrolysin had no advantage over speech therapy alone for either mRS or BI at 30 days. At 60 days, cerebrolysin had a slight, non-significant advantage for the mRS endpoint, but there was no signal of benefit for the BI. However, cerebrolysin had a statistically significant, albeit modest, advantage for both of these secondary endpoints at 90 days (both P < .001).

Cerebrolysin was well tolerated in this study. This is consistent with the results of numerous other published studies of cerebrolysin, but anaphylaxis is a risk, according to several case reports. The most recent was published this year.

Limited Availability

The European Medicines Agency has characterized cerebrolysin as safe, but of the approximately 50 countries in which this medicine is now approved, only a handful are in Europe. Besides Romania, these include Austria, Germany, and Poland. But there are scattered approvals elsewhere, including South Korea, Mexico, Vietnam, and Ukraine. Most commonly, cerebrolysin is indicated as an adjunct for the acute treatment of stroke.

Given the mixed findings with this agent despite several decades of experimental and clinical studies, one of the moderators of the late-breaking study in which the ECASS results were presented indicated that multinational controlled studies are needed. According to Ana C. de Souza, MD, PhD, these studies are needed not only for the treatment of stroke aphasia but also for the treatment of other conditions and diseases associated with neurodegeneration.

Without high-quality trials of sufficient size to confirm clinical utility, the promise of both the experimental results remains difficult to interpret, according to de Souza, a clinician and researcher associated with Hospital Moinhos de Vento, Porto Alegre, Brazil.

The study received funding from EVER Neuro Pharma GmbH. Muresanu and de Souza reported no potential financial conflicts of interest.