Cerebrolysin

What it is

Cerebrolysin is a complex peptide preparation derived from purified porcine brain tissue, containing a mixture of low-molecular-weight neuropeptides and amino acids. The molecular weights of the components are below 10 kDa. In laboratory studies, some of its peptide fragments have been reported to show activity resembling brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).

Cerebrolysin was originally developed by Ebewe Pharmaceuticals (now part of Ever Neuro Pharma) in Austria and has been marketed outside the US since the 1950s. It is approved in over 50 countries for neurological indications including ischemic stroke, traumatic brain injury, and dementia. It is not FDA-approved for any use in the United States.

Cerebrolysin has been the subject of many published clinical trials, mostly conducted outside the US. FDA approval has not been pursued, partly due to the complex nature of the preparation (a peptide mixture rather than a single defined molecule) and partly due to regulatory and commercial factors.

Mechanism of action

Proposed mechanisms come from laboratory and animal research:

• BDNF-like activity: in laboratory studies, components have been reported to mimic some effects of brain-derived neurotrophic factor on neuronal survival and synaptic plasticity.
• NGF-like activity: nerve growth factor-like effects on cholinergic neurons have been reported in cell and animal models.
• Cell survival signaling: in animal models of ischemic injury, Cerebrolysin was associated with changes in markers of programmed neuronal death.
• Inflammatory signaling: in animal models, it was associated with changes in markers of neuroinflammation.
• Glutamate excitotoxicity: laboratory studies have reported changes in glutamate-mediated neuronal damage.
• Synaptic plasticity: animal studies have reported changes in synaptic markers after exposure.
• Mitochondrial function: changes in neuronal energy metabolism markers have been reported in laboratory models.

Research findings

Studies conducted mainly in Europe and Asia have reported the following; these findings have not been evaluated by the FDA:

Ischemic stroke: multiple RCTs and Cochrane reviews have evaluated Cerebrolysin in acute and subacute ischemic stroke. Results are mixed, and Cochrane reviews did not find clear evidence of benefit on mortality or dependency.

Traumatic brain injury: studies in moderate-to-severe TBI have been published; benefit in people has not been established.

Vascular cognitive impairment and Alzheimer disease: studies have been published; benefit in people has not been established.

Pediatric neurodevelopmental conditions: it has been studied in some countries in developmental conditions; evidence is limited.

Post-COVID neurological symptoms: formal trial data are limited.

Well-controlled human trials establishing effectiveness and safety by US regulatory standards are lacking.

Side effects and contraindications

Human safety has not been established by the FDA, and long-term effects are unknown. Reported concerns include allergic-type reactions, particular caution in people with porcine product allergy, severe renal impairment, or seizure disorders, and the absence of safety data in pregnancy and breastfeeding. Products sold outside regulated channels may vary in purity, dose, and sterility.

What we don’t yet know

Despite the international literature, clinical trial results have been mixed, and Cerebrolysin’s role remains contested. Which people, if any, might benefit is not defined. Long-term outcomes are less well characterized than short-term outcomes. How Cerebrolysin compares with other interventions has not been established in head-to-head studies. The complex multi-component nature of the preparation makes precise mechanistic characterization difficult and complicates regulatory pathways.