Cortagen
AEDP peptide, Ala-Glu-Asp-Pro, cortexin-derived tetrapeptide
Cortagen is a four-amino-acid peptide from the Khavinson series, designed by amino acid analysis of Cortexin, a crude bovine brain cortex extract used in Russian neurology. Its published record runs to about fifteen indexed papers and is concentrated on peripheral nerve regeneration in rats in the early 2000s. There is no controlled human trial and no independent replication outside the originating research network.
Mechanism
Cortagen is a tetrapeptide with no identified receptor, and the mechanism attributed to it is the standard Khavinson model: nuclear entry and sequence-selective binding to promoter DNA or to histones, altering chromatin accessibility and gene transcription. Its design logic is worth understanding because it is characteristic of the whole series. Cortexin is a polypeptide extract of calf brain cortex, long used in Russia for neurological indications. Amino acid analysis of that extract identified which residues were abundant, and a short peptide was then synthesised from those residues on the assumption that the extract's activity resided in a short motif of that composition. This is an inference from composition, not from isolation of an active fraction, and it is a weak basis for asserting that the resulting synthetic peptide reproduces the extract's biology.
The one piece of mechanistic work with a defined readout is a 2004 microarray study in Neuroendocrinology Letters that profiled gene expression changes in mouse heart after Cortagen administration and reported effects on multiple transcripts. Microarray studies of this vintage were notoriously prone to false discovery, and the finding has not been followed up with modern transcriptomics or validated at the protein level. Note also the oddity that a peptide nominally assigned to brain cortex was profiled in heart tissue, which is difficult to square with the organ-matching premise of the series.
What the research shows
The Cortagen literature is thin and old, at about fifteen indexed records. The most concrete results are two rat sciatic nerve studies from 2000 and 2002 reporting accelerated functional recovery after nerve crush injury, published in Bulletin of Experimental Biology and Medicine and Doklady Biological Sciences respectively. A 2007 rat study reported that injections of Cortagen and Epitalon reduced lipid peroxidation products and oxidative modification of proteins in serum and cerebral cortex, though the same study reported that antioxidant activity was suppressed rather than raised, which complicates a simple antioxidant reading. A 2011 Russian pharmacology paper examined Cortexin and Cortagen as correcting agents in metabolic and functional brain disturbances in a chronic cerebral ischaemia model. A 2004 microarray paper profiled gene expression changes in mouse heart. There is also a set of in vitro studies examining tetrapeptides including Cortagen on lymphocyte chromatin structure.
What does not exist is equally important. There is no registered clinical trial of Cortagen. There is no published human pharmacokinetic or toxicology study. There is no independent replication of the nerve regeneration findings by a laboratory outside the Russian network. There is essentially no modern work: the field has been static for over a decade, which for a compound with claimed neuroregenerative activity is itself informative. A genuinely promising nerve regeneration agent would normally attract follow-up.
Evidence assessment
Preclinical only
The published record is confined to rat nerve injury and oxidative stress models, one dated microarray study and in vitro chromatin work, all from the originating research network, with no human trial and no independent replication.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
Effect of tetrapeptide cortagen on regeneration of sciatic nerve Preclinical only
Cortagen accelerated functional recovery of the injured nerve compared with control.
The delayed effect of cortagen on the restoration of injured nerve function Preclinical only
Reported persisting improvement in nerve function recovery after Cortagen administration.
Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray Preclinical only
Reported changes in expression of multiple transcripts after Cortagen administration.
Effects of bioactive tetrapeptides on free-radical processes Preclinical only
Both peptides decreased lipid peroxidation products and oxidative modification of proteins, though serum and cortical antioxidant activity was suppressed rather than increased.
Cortexin and cortagen as correcting agents in functional and metabolic disorders in the brain in chronic ischemia Preclinical only
Both the crude extract and the synthetic tetrapeptide were reported to correct functional and metabolic brain disturbances.
Effects of short peptides on lymphocyte chromatin in senile subjects Preclinical only
Short peptides including Cortagen were reported to alter heterochromatin structure in lymphocytes from elderly subjects.
Safety
No formal safety data. No toxicology, no human adverse event record, no dose-ranging study. Absence of reported harm reflects absence of investigation. Material sold online is unregulated, and although the AEDP sequence is now confirmable against NLM indexing, no published analytical reference standard exists against which a buyer could check identity or purity.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | No MHRA marketing authorisation. Supply for human use engages the Human Medicines Regulations 2012 irrespective of a 'research use only' designation. |
| United States | Not approved by the FDA, never the subject of an investigational new drug application, and not present in any clinical trial registry. Sold only as a research chemical. |
| WADA (sport) | Not individually named on the Prohibited List but captured by section S0 (non-approved substances), prohibited at all times. |
Questions
It was designed by amino acid analysis of Cortexin, a crude bovine brain cortex extract used in Russian neurology. Researchers identified abundant residues in the extract and synthesised a short peptide from them. That is an inference from composition, not isolation of an active fraction, so it does not follow that the peptide reproduces the extract's biology.
No. There is no registered clinical trial, no human pharmacokinetic study and no controlled human outcome data. The published record consists of rat nerve injury and oxidative stress studies, one dated microarray experiment and ex vivo chromatin work.
Two rat sciatic nerve crush studies from 2000 and 2002 reported accelerated functional recovery. Neither has been independently replicated in over twenty years, and no human study has tested the claim.
Ala-Glu-Asp-Pro (AEDP). This is confirmable: the US National Library of Medicine indexes Cortagen as a named chemical supplementary concept with Ala-Glu-Asp-Pro as an entry term, so the assignment does not rest only on vendor descriptions.