Cortagen

What it is. Cortagen is Ala-Glu-Asp-Pro (AEDP), designed from brain cortex extract amino acid composition in the Khavinson programme - the short-peptide counterpart to Cortexin, the cortical extract used clinically in Russia [5].

The nerve regeneration result. Rats had the sciatic nerve transected and sutured, then received 10 µg/kg cortagen intramuscularly daily for ten days. The growth rate of regenerating nerve fibres rose 27% and conduction velocity in them rose 40% [1]. A second paper examined the delayed effect on restoration of injured nerve function [2].

This deserves credit for what it is: a defined model, a stated per-kilogram dose, and two quantified physiological outcomes. Across the whole Khavinson short-peptide literature, that combination is rare - most of it is chromatin in cultured cells or gene expression counts. It is still a single group's result in a single model, unreplicated elsewhere.

The rest. A DNA microarray study of cortagen's effect on gene expression in mouse heart [3], work on tissue-specific effects of peptides [6], and a study of short peptides on thymocyte blast transformation and sphingomyelin-pathway signalling [7].

The human report. One Russian-language paper describes Cortexin and Cortagen as correcting agents in functional and metabolic brain disorders in chronic ischaemia [4]. It combines the peptide with a different preparation, is not a controlled trial, and is available in English only as an abstract.

Context worth carrying. Cortexin, the cortical extract, is a hydrolysate of the same kind as Cerebroprotein Hydrolysate - and where that class has been assessed by Cochrane, the results have been unfavourable [8]. Cortagen is a defined peptide rather than a hydrolysate, which is a genuine difference, but it inherits the same clinical tradition and the same absence of independent trials.

The family mechanism applies: a short peptide entering cells and the nucleus and altering gene expression [9][10]. The microarray work in mouse heart is cortagen's contribution to that case [3], alongside the programme's broader claim of tissue-specific effects demonstrated in organ culture [6].

For the nerve result specifically, no mechanism has been established. The paper reports faster fibre growth and higher conduction velocity after nerve injury [1]; it does not identify what cortagen does to Schwann cells, axons or the regenerating growth cone to produce that. The effect on thymocyte sphingomyelin signalling [7] is a separate observation in a different cell type and does not obviously connect.

So there is a measured physiological effect without a mechanism, and a proposed mechanism without a demonstrated link to the physiological effect. Both halves are real; the bridge between them has not been built.

The free tetrapeptide Ala-Glu-Asp-Pro, supplied lyophilised and given intramuscularly in the animal work [1]. Oral products are sold in Russia without a published absorption study.

No adverse effects are reported in the available literature, and no safety or toxicology study has been published. There is no pharmacokinetic data in any species and no human safety data.

The dosing in the nerve study - 10 µg/kg for ten days [1] - is very low by the standards of most injected peptides, which limits the plausible magnitude of any off-target effect at that exposure. It also means nothing is known about what higher or longer exposure does, and nothing in the published literature has tested it.

The provenance caveat applies as it does across this group: one programme, largely one journal family, no independent replication.

No interaction studies exist. The human report pairs Cortagen with Cortexin, the cortical extract [4], but describes them as correcting agents in the same clinical setting rather than studying the combination as such.