Trofinetide is an Orally active IGF-1 Peptide Synthetic Analog for Rett Syndrome

Rett syndrome (RTT) is a severe neurodevelopmental disease with complex medical comorbidities. Generally, Methyl-CpG-binding protein 2 (MECP2) is a ubiquitously expressed transcriptional regulator. However, MECP2 can cause Rett syndrome. Researchers have found that mice deficient in MeCP2 have a range of physiological and neurological abnormalities.

Insulin-like Growth Factor 1 (IGF-1) is a pleiotropic growth factor. Firstly, It strongly promotes neuronal cell survival and synaptic maturation. Next, IGF-1 also facilitates the maturation of functional plasticity in the developing cortex. Thirdly, treatment with IGF-1 peptide increases the brain weight of the mutant mice. In addition, treatment with IGF-1 peptide not only partially restores spine density and synaptic amplitude, but also increases PSD-95 and stabilizes cortical plasticity to wild-type levels. In summary, IGF-1 may be a strategy for the research of RTT. Today, we will introduce an IGF-1 peptide synthetic analog – Trofinetide.

Trofinetide is an Oral active IGF-1 Peptide Synthetic Analog for Rett Syndrome

Trofinetide (NNZ-2566) is an IGF-1 peptide synthetic analog with neuroprotective activity in animal models of brain injury. It has a good elimination half-life and oral bioavailability.

 In vitro, Trofinetide significantly attenuates apoptotic cell death in primary striatal cultures. It suggests attenuation of apoptosis may be a mechanism of action underlying its neuroprotective effects. In vivo, Trofinetide can reduce injury size in rats subjected to focal stroke. Secondly, Trofinetide (intravenous infusion, 3 – 10 mg/kg/h, 4 h) significantly reduced the infarct area as assessed on day 5. Thirdly, Trofinetide (oral, 30 – 60 mg/kg) has neuroprotective efficacy in the MCAO model. MeCP2 mutant mice with an active peptide fragment of IGF-1 extend the life span of the mice, improve locomotor function, ameliorate breathing patterns, and reduce irregularity in heart rate.

In brief, Trofinetide is an orally active IGF-1 peptide synthetic analog and can be used for the research of RTT or CNS disorders.



[1] Neul JL, et al. Ann Neurol. 2010;68(6):944-950.

[2] Tropea D, et al. Proc Natl Acad Sci U S A. 2009;106(6):2029-2034.