IGF-1

In simple words

IGF-1 (mecasermin) is the protein through which growth hormone acts on tissues; its recombinant version is approved as a drug. It is used for severe primary IGF-1 deficiency, when the body does not respond to growth hormone, and is being studied in Rett syndrome.

What this molecule is

70 aa, 3 disulfide bonds (A6-A11, A7-B7, A20-B19). Recombinant human IGF-1. ~7649 Da. ~50% homology with proinsulin.

Why it is studied

FDA-approved (Increlex®, 2005). Severe primary IGF-1 deficiency and Laron syndrome (GH insensitivity). The only therapy when the GH axis is not working. 2025 systematic review (PMID: 41174329): effective in Rett syndrome.

How it works

IGF-1R (tyrosine kinase) → IRS-1/2 → PI3K/Akt (↑cell survival, ↑GLUT4 translocation) + RAS/MAPK/ERK (↑proliferation). In the CNS: ↑neurogenesis, ↑synaptic plasticity, ↑myelination. In muscle: ↑protein synthesis via mTOR/S6K1.

Doses used in studies

Per the FDA label, it was given SC 2 times a day, within 20 min before or after a meal. Starting dose 0.04 mg/kg, increased by 0.04 mg/kg every 1-2 weeks up to a maximum of 0.12 mg/kg 2 times a day. The label requires food intake (hypoglycemia in 65%).

Combined with in studies

• IGFBP-3 — complex ↑T½
• GH — NOT at the same time: supraphysiological levels

Level of evidence

Level A Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. FDA-approved 2005. Many clinical studies.

Important to know

⚠️ Rx only: by doctor's prescription only. Hypoglycemia in 65%! Adenoid hypertrophy, ↑intracranial pressure, scoliosis. Contraindicated in tumors (IGF-1 is a mitogen). DO NOT confuse with IGF-1 LR3.

Studies in PubMed

1. Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndrome. (Eur J Endocrinol, 2021)
2. Mecasermin for the treatment of Rett Syndrome: a systematic review. (Neurogenetics, 2025)
3. Molecular Signatures of Response to Mecasermin in Children With Rett Syndrome. (Front Neurosci, 2022)
4. Alterations in Stem Cell Populations in IGF-1 Deficient Pediatric Patients Subjected to Mecasermin (Increlex) Treatment. (Stem Cell Rev Rep, 2023)
5. Clinical characteristics and treatment efficacy in patients with primary severe IGF-1 deficiency treated with recombinant IGF-1. (Front Pediatr, 2024)
6. Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. (Int J Biochem Cell Biol, 1996)