Cerebrolysin

An Austrian prescription injectable made from enzymatically digested pig brain protein — a mixture of sub-10 kDa peptides and free amino acids, approved for stroke, dementia, and head injury in parts of Europe and Asia but never reviewed by the FDA.

Also referenced as: Cerebrolysin concentrate, FPF-1070, porcine brain-derived peptide preparation, Cerebrolysinum

Also appears in: Cognitive

What is Cerebrolysin?

Cerebrolysin is not a peptide in the sense the rest of this library uses the word. It has no sequence, no single molecular weight, and no named active ingredient: the approved Austrian labeling defines it only as 215.2 mg per mL of a “proteolytic peptide fraction from porcine brain protein” in water, adjusted with sodium hydroxide. The most-cited characterization, published by investigators working with the original manufacturer, puts the material at roughly 25% low-molecular-weight peptides under 10 kDa and roughly 75% free amino acids, measured by total nitrogen (Hartbauer et al., Journal of Neural Transmission, 2001;108(4):459–473). It is produced by standardized enzymatic digestion of purified pig brain protein and sold as a clear amber solution in ampoules and vials.

It was developed by the Austrian firm EBEWE and is now held by EVER Neuro Pharma GmbH (Unterach, Austria); the current Austrian marketing authorization was granted on 25 March 1996 and covers supportive treatment of cerebrovascular disorders, with Alzheimer-type and vascular dementia, post-stroke deficits, and head injury (concussion and contusion) named specifically. It is registered as a prescription drug across Central and Eastern Europe, Russia and the post-Soviet states, China, Korea, and parts of Southeast Asia, Latin America, and the Middle East, and it is the reference compound against which “Cerebrolysin-like” extracts such as Cortexin are measured. It reaches American readers as a finished foreign pharmaceutical that circulates through export resellers into nootropic and research-market catalogs, with no FDA review of any kind.

How it works

Because the product is a mixture, mechanism work describes what the preparation does rather than what a molecule does. The manufacturer’s framing is that Cerebrolysin “mimics” endogenous neurotrophic factors; the published evidence is almost entirely preclinical and much of it sponsor-funded.

• The peptide fraction, not the amino acids, carries the trophic activity in vitro. In low-serum cultures of embryonic chick cortical neurons, Cerebrolysin and a matched artificial amino-acid mixture both raised viability at four days, but only Cerebrolysin sustained viability and reduced the share of apoptotic nuclei at eight days (Hartbauer et al., Journal of Neural Transmission, 2001;108(4):459–473). This is the experiment usually cited to argue that the preparation is more than a nutrient solution.
• Sonic hedgehog–dependent neurogenesis and oligodendrogenesis after experimental stroke. In adult rat subventricular-zone progenitors, Cerebrolysin increased proliferation and differentiation into neurons and myelinating oligodendrocytes alongside upregulation of Shh and its receptors Patched and Smoothened; the Smoothened inhibitor cyclopamine abolished the effect in vitro and reversed both the neurorestorative changes and the functional recovery in rats treated from 24 hours after embolic stroke (Zhang et al., Stroke, 2013;44(7):1965–1972; a correction to this paper was published in Stroke in February 2025). The same group had earlier reported increased neurogenesis and better behavioral outcomes, without a reduction in infarct volume, with treatment starting 24–48 hours after embolic stroke in rats (Zhang et al., Journal of Neuroscience Research, 2010;88(15):3275–3281).
• Reduced amyloid production via APP processing and kinase regulation in transgenic mice. Six months of Cerebrolysin in APP-transgenic mice improved water-maze performance and lowered synaptic pathology and amyloid burden, associated with reduced full-length APP maturation rather than increased Aβ degradation (Rockenstein et al., Journal of Neuroscience Research, 2006;83(7):1252–1261). A review by the same senior author, published in a Cerebrolysin-focused journal supplement, attributes the amyloid and tau effects to regulation of GSK-3β and CDK5 activity and summarizes stroke-model data on calpain inhibition, apoptosis, infarct size, and edema (Masliah and Díez-Tejedor, Drugs of Today, 2012;48 Suppl A:3–24).
• Anti-excitotoxic action in the delayed hours after ischemia-reperfusion. Independent rodent work reports that Cerebrolysin given 3 to 12 hours after ischemia-reperfusion, or after glutamate exposure in cortical cultures, reduced neuronal death and restrained the upregulation of extrasynaptic NR2B-containing NMDA receptors (Sarode et al., Metabolic Brain Disease, 2023;38(7):2401–2416), one of the few mechanism papers with no manufacturer involvement.

Conventional pharmacokinetics do not exist for this product. The Austrian labeling states that because the peptide fraction consists of short peptides similar or identical to endogenous ones, pharmacokinetic parameters cannot be measured directly, that blood-brain barrier passage is inferred from preclinical experiments showing identical central effects after intracerebroventricular and peripheral administration, and that a neurotrophic activity is detectable in plasma for up to 24 hours after a single dose by pharmacodynamic rather than analytical measurement.

Research status

Cerebrolysin has one of the largest clinical literatures of any entry in this library, much of it in English-language journals with pre-registered trials. The evidence is heterogeneous in quality, heavily sponsor-shaped, positive on short-term composite and functional scales in several trials, null on the hardest endpoints, and not approved by the FDA, under the EU centralized procedure, or by the UK MHRA.

Acute ischemic stroke — the largest trial was negative. CASTA randomized 1,070 patients in four Asian countries within 12 hours of hemispheric stroke to Cerebrolysin infusions for 10 days or saline, both on aspirin. The confirmatory endpoint, a combined global test of modified Rankin Scale, Barthel Index, and NIHSS at 90 days, showed no difference. A post hoc analysis in patients with NIHSS above 12 reported a trend favoring Cerebrolysin and 90-day mortality of 10.5% versus 20.2% (Heiss et al., Stroke, 2012;43(3):630–636; NCT00868283); the sponsor was EVER Neuro Pharma, and that mortality subgroup, which its materials feature prominently, was exploratory.

The Cochrane review of acute ischemic stroke, in its 2023 update, included seven RCTs with 1,773 participants (one of them the Cortexin trial). At moderate certainty, Cerebrolysin or Cerebrolysin-like peptide mixtures probably make little or no difference to all-cause death (RR 0.96, 95% CI 0.65 to 1.41; 6 trials, 1,689 participants). The review also found a probable increase in the number of people with non-fatal serious adverse events (RR 2.39, 95% CI 1.10 to 5.23; 3 trials, 1,335 participants; moderate certainty), more pronounced with the highest-exposure schedule (RR 2.87, 95% CI 1.24 to 6.69; 2 trials, 1,189 participants). The reviewers judged selective-outcome-reporting risk unclear across all Cerebrolysin trials and noted that the manufacturer supported the three multicenter studies with drug, placebo, randomization codes, grants, or statisticians (Ziganshina et al., Cochrane Database of Systematic Reviews, 2023;10:CD007026).

Two other meta-analyses point the other way on safety: a pooled analysis of twelve RCTs (2,202 patients) from the Cluj-Napoca group that runs the CARS and CAPTAIN programs found no significant difference in serious adverse events versus placebo (Strilciuc et al., Pharmaceuticals, 2021;14(12):1297), and an independent 2025 meta-analysis of fourteen RCTs (2,884 patients) reported a 1.39-point greater NIHSS improvement with Cerebrolysin (95% CI 0.53 to 2.25) and no difference in functional independence, serious adverse events, or mortality (Patel et al., Cureus, 2025;17(8):e91054). The discrepancy with Cochrane comes from trial selection and from how non-fatal and fatal events are split.

Post-stroke rehabilitation — the positive trial, and its confirmatory successor. CARS randomized 208 patients with ischemic stroke to 30 mL daily or saline for 21 days starting 24–72 hours after onset, alongside a standardized rehabilitation program. The primary endpoint, Action Research Arm Test score at day 90, favored Cerebrolysin with a Mann-Whitney estimator of 0.71 (95% CI 0.63 to 0.79; P<0.0001), and a multivariate analysis across twelve scales gave a small-to-medium effect (MW 0.62). The authors themselves described the study as exploratory and called for confirmation in a large trial (Muresanu et al., Stroke, 2016;47(1):151–159). An identically designed second trial, CARS-2, followed; a pre-planned individual-patient-data meta-analysis of both (N=442) reported a smaller pooled ARAT effect (MW 0.62) that remained significant (Guekht et al., Neurological Sciences, 2017;38(10):1761–1769). A separate Korean Phase 4 trial in 70 patients is reported as positive mainly for the severely impaired subgroup (Chang et al., BMC Neurology, 2016;16:31). The confirmatory trial the CARS authors asked for — CARS-CT, 416 patients, placebo-controlled, double-blind, sponsored by a non-commercial foundation in Cluj-Napoca — was authorized in the EU in July 2025 and began recruiting in Romania in October 2025 (EU CT 2025-521350-41-01). Until it reports, the rehabilitation claim rests on two trials totaling 442 patients, the first of which was labeled exploratory by its own authors.

The largest recent dataset is not a randomized trial. C-REGS2, an open-label comparative-effectiveness study across 16 countries (2018–2024), analyzed 1,769 patients with moderate stroke, 1,021 treated and 748 controls, and reported superiority on 90-day mRS (MW 0.6157; 95% CI 0.5910 to 0.6404) with no safety differences (Vosko et al., International Journal of Stroke, 2025;20(9):1060–1070); several authors, including the biostatistician, disclose EVER Neuro Pharma honoraria, and an observational registry cannot replace the blinded confirmation that CASTA failed to supply.

Post-stroke aphasia. ESCAS, a randomized, double-blind, placebo-controlled pilot of speech therapy with or without Cerebrolysin in 132 patients with nonfluent aphasia at two Romanian centers, reported a 14.8-point greater improvement on the Western Aphasia Battery (95% CI 9.5 to 20.1) (Homberg et al., Stroke, 2025;56(4):937–947). It is a pilot and is labeled as one.

Vascular dementia. The 2019 Cochrane update identified six RCTs with 597 participants, none new since 2013, with industry funding wherever funding was reported. Pooled cognition data (three studies, 420 people) gave an SMD of 0.36 (95% CI 0.13 to 0.58) and pooled global response (two studies, 379 people) a risk ratio of 2.69 (95% CI 1.82 to 3.98), both very-low-quality evidence; the authors concluded that any benefit may be too small to be clinically meaningful (Cui et al., Cochrane Database of Systematic Reviews, 2019;11:CD008900). The single best trial in that set, a 242-patient Russian multicenter double-blind study, reported 24-week ADAS-cog+ responder rates of 82.1% versus 52.2% (Guekht et al., Journal of Stroke and Cerebrovascular Diseases, 2011;20(4):310–318).

Alzheimer’s disease. The Alzheimer’s trials are older and mostly from the manufacturer’s own network: a 28-week double-blind trial in 149 patients reported a CGI responder rate of 63.5% versus 41.4% (Ruether et al., International Clinical Psychopharmacology, 2001;16(5):253–263); a 24-week dose-ranging trial in 279 patients found cognition improved only at the lowest of three doses, an inverted-U dose-response the authors acknowledged (Alvarez et al., European Journal of Neurology, 2006;13(1):43–54); and a three-arm trial against donepezil and the combination found no significant between-group differences on cognitive, functional, or behavioral measures (Alvarez et al., Current Alzheimer Research, 2011;8(5):583–591). A meta-analysis of six placebo-controlled trials found a significant cognitive effect at 4 weeks (SMD −0.40; 95% CI −0.66 to −0.13) that was no longer significant at 6 months; two of its authors were an EVER employee and the sponsor’s contract statistician (Gauthier et al., Dementia and Geriatric Cognitive Disorders, 2015;39(5–6):332–347). Cerebrolysin is not a licensed Alzheimer’s treatment in the United States or the United Kingdom and has never been through the EU centralized procedure.

Traumatic brain injury. CAPTAIN II, a single-center randomized double-blind placebo-controlled trial, analyzed 139 patients with moderate-to-severe TBI and reported a small-to-medium effect on a 13-scale composite at day 90 (MW 0.59; 95% CI 0.52 to 0.66) with comparable safety (Muresanu et al., Neurological Sciences, 2020;41(5):1171–1181); a prospective meta-analysis of the two CAPTAIN trials, 185 patients in total, reported MW 0.60 (Vester et al., Neurological Sciences, 2021;42(11):4531–4541). These are the best TBI data, fewer than 200 patients, with the sponsor’s contract biostatistician as first author of the pooled analysis.

What is registered now. A ClinicalTrials.gov intervention search returned 43 studies as of October 2026, nine of them active: the sponsor’s own Phase 2 crossover trial in 30 patients with CADASIL in Czechia (CERICA, NCT05755997, active but no longer recruiting, no results posted); investigator-initiated Phase 4 studies in Korea on post-stroke aphasia and prolonged disorders of consciousness; a not-yet-recruiting Phase 2 thrombectomy-adjunct study in Taiwan; and smaller academic trials in Poland, Slovenia, Egypt, and Vietnam. None has a US site and none is aimed at a US marketing application. Published pilot-stage work beyond that — the CLINCH protocol for an 88-patient open-label pilot in lobar intracerebral hemorrhage (Kobayashi et al., Frontiers in Neurology, 2025;16:1602956) and a 2026 propensity-matched cohort of thrombectomy patients (Staszewski et al., Translational Stroke Research, 2026;17(2):28) — is feasibility- and observational-grade.

Common dosage forms

Cerebrolysin has exactly one authorized pharmaceutical form in its home market: a sterile aqueous solution of 215.2 mg/mL peptide concentrate, clear and amber, for injection or dilution into an infusion. The Austrian labeling lists:

• Glass ampoules of 1, 2, 5, 10, and 20 mL.
• Multi-dose (piercable) vials of 20, 30, and 50 mL, the hospital infusion presentations.

Two format notes matter outside its registered markets. First, there is no lyophilized or powder presentation of Cerebrolysin anywhere in the labeling: a “Cerebrolysin” sold as powder for reconstitution has no counterpart in the authorized product. Second, what circulates outside Europe and Asia is the finished branded pharmaceutical moved through export channels, not a bulk research chemical; there is no sequence to synthesize, and no FDA-approved product, 503A bulk-substance listing, or licensed US compounding route exists for a porcine brain hydrolysate.

Key considerations

• Approved abroad, never reviewed here. Cerebrolysin is a prescription-only drug in Austria and many other countries. Its Research Market status reflects regional approvals with no US program; the nine active registered trials are academic or sponsor studies outside the United States, none directed at US approval, and do not change that classification. The FDA has not reviewed it, it is not on the section 503A bulk drug substances list, and the manufacturer’s own product page states that it is not registered with the FDA and not approved for sale or distribution in the United States.
• The evidence is large, mixed, and sponsor-shaped. The one adequately powered placebo-controlled trial in acute stroke (CASTA) missed its primary endpoint; the most-cited positive trial (CARS) enrolled 208 patients and was labeled exploratory by its own authors, with its confirmatory successor only recruiting since October 2025. The Cochrane reviews rate the stroke and vascular-dementia evidence as moderate-to-very-low certainty and find no mortality benefit. EVER Neuro Pharma supplied drug, placebo, randomization, grants, or statistics to the major trials, and its staff and contract biostatistician appear as co-authors on CARS, CAPTAIN II, the Alzheimer’s meta-analysis, and C-REGS2; none of this makes the results wrong, but independent replication is thin.
• The safety record is better than the class average but not clean. The approved labeling lists hypersensitivity, status epilepticus, and severe renal impairment as contraindications, warns that seizure frequency may rise in patients with epileptic disorders, records very rare allergic reactions up to shock-like states and isolated grand mal seizures, and flags an interaction with antidepressants and MAO inhibitors. The 2023 Cochrane review’s moderate-certainty finding of roughly doubled non-fatal serious adverse events in acute stroke is the most important independent safety signal and contradicts the uniformly benign tolerability reported in sponsor publications; neither should be quoted without the other.
• Source tissue and lack of a defined active change what verification can mean. Cerebrolysin is made from pig brain, and the label carries no information on sourcing controls. No naturally occurring prion disease has been documented in pigs, which distinguishes porcine from bovine cortical extracts, and no transmission event has ever been attributed to this product, but a central-nervous-system hydrolysate still raises the sourcing question. More practically, there is no reference standard: a certificate of analysis cannot confirm identity and purity for an undefined hydrolysate the way it can for a synthetic peptide, and nothing an independent lab can run on an ampoule will confirm it matches the trial material.
• Several unrelated or near-related products share the name or the niche. Cortexin is a separate cortical lyophilizate from a Russian manufacturer, included in the Cochrane stroke review as a “Cerebrolysin-like agent” but not the same product; Chinese “cerebroprotein hydrolysate” products are domestic hydrolysates marketed as equivalents with no published equivalence study, so trials of them should not be read as trials of Cerebrolysin. Cerebrolysin also carries CAS number 12656-61-0 and the older code FPF-1070, and “Cerebrolysinum” is a Latinized labeling form; any citation offered in support of the drug should be checked for which preparation was studied.