A randomized controlled trial of Everolimus for neurocognitive symptoms in PTEN hamartoma tumor syndrome. Human molecular genetics Srivastava, S., Jo, B., Zhang, B., Frazier, T., Gallagher, A. S., Peck, F., Levin, A. R., Mondal, S., Li, Z., Filip-Dhima, R., Geisel, G., Dies, K. A., Diplock, A., Eng, C., Hanna, R., Sahin, M., Hardan, A. 2022


PTEN hamartoma tumor syndrome (PHTS) is a complex neurodevelopmental disorder characterized by mTOR (mechanistic target of rapamycin) overactivity. Limited data suggest that mTOR inhibitors may be therapeutic. No placebo-controlled studies have examined mTOR inhibition on cognition and behavior in humans with PHTS with/without autism.We conducted a 6-month phase II, randomized, double-blinded, placebo-controlled trial to examine the safety profile and efficacy of everolimus (4.5 mg/m2) in individuals (5-45 years) with PHTS. We measured several cognitive and behavioral outcomes, and electroencephalography (EEG) biomarkers. The primary endpoint was a neurocognitive composite derived from Stanford Binet-5 (SB-5) nonverbal working memory score, SB-5 verbal working memory, Conners' Continuous Performance Test hit reaction time, and Purdue Pegboard Test score.Forty-six participants underwent 1:1 randomization: n?=?24 (everolimus) and n?=?22 (placebo). Gastrointestinal adverse events were more common in the everolimus group (p?

View details for DOI 10.1093/hmg/ddac111

View details for PubMedID 35594551