Trofinetide (acetate)

Trofinetide is a derivative of the neuroprotective tripeptide Gly-Pro-Glu, an N-terminal sequence found in insulin-like growth factor-1 (IGF-1).¹ It decreases cell death induced by the protein phosphatase inhibitor okadaic acid in primary rat embryonic striatal neurons when used at a concentration of 10 nM. Trofinetide reduces brain expression of mRNA encoding IL-1β, TNF-α, IL-6, and E-selectin in a rat model of neuroinflammation induced by a penetrating ballistic-like brain injury.² It reduces cortical and striatal infarct area in a rat model of brain injury induced by middle cerebral artery occlusion (MCAO) when administered at doses of 30 and 60 mg/kg.¹ Trofinetide (100 mg/kg per day) reduces the number of dendritic spines and reverses deficits in social recognition and contextual fear conditioning, as well as decreases testicular weight gain, in an fmr1^-/- knockout mouse model of fragile X syndrome.³ Formulations containing trofinetide have been used in the treatment of Rett syndrome.