Growth factor

IGF-1 DES is IGF-1 with its first three amino acids — glycine, proline, glutamate — clipped off. Unlike most designer peptides it is a real thing that occurs in the body: it has been isolated from bovine colostrum, human brain and porcine uterus, and an acid protease in serum makes it from intact IGF-1. Losing the glutamate at position 3 costs it almost all of its affinity for the IGF binding proteins, so it is about ten times more potent than IGF-1 at growing cells in a dish. In rats it is cleared roughly four times faster than IGF-1 and distributes into tissue far more readily, and in catabolic models it improved nitrogen balance and slowed muscle protein breakdown. Thirty years on from the review that said its clinical opportunities had not yet been evaluated, they still have not been: there is no published human trial.

IGF-1 LR3 is a laboratory-engineered version of insulin-like growth factor-1: the natural protein with glutamate at position 3 swapped for arginine and a 13-amino-acid extension bolted onto the N terminus. Both changes weaken its grip on the IGF binding proteins that normally hold IGF-1 in circulation, so more of it reaches the IGF-1 receptor. It was designed as a cell-culture and livestock research reagent, never as a medicine, and it has never been given to a person in a published trial. The animal work is not the story the bodybuilding market tells: in pigs a four-day infusion reduced daily weight gain and food intake and suppressed growth hormone, and in guinea pigs it enlarged the gut, kidneys, adrenals and spleen without increasing overall growth. It is prohibited in sport, and at least one black-market vial turned out to contain the His-tagged purification reagent rather than anything intended for injection.

Mechano growth factor is a splice variant of the IGF-1 gene, IGF-1Ec in humans, switched on in muscle after mechanical loading or damage. Its distinctive part is the E domain, and what is sold as "MGF" is a synthetic 24-amino-acid peptide copied from the end of that domain. PEG-MGF adds polyethylene glycol to slow its disappearance. The E peptide has real preclinical credentials: it pushes human muscle satellite cells to proliferate and fuse, and it does so through a receptor that is not the IGF-1 receptor. It also has three problems. It did not work on satellite cells from old muscle, the age group the sarcopenia pitch targets; the same peptide drives growth in prostate cancer cells, and the IGF-1Ec transcript is overexpressed in prostate and colorectal tumours; and there is no published study of the PEGylated form in any species, let alone a human trial.