Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling.
The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50-800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at baseline vs. 2.33 at week 5 (P < 0.001) and 4.83 at baseline vs. 3.86 at week 5 (P < 0.001). Parental Vanderbilt scores showed significant improvement for subjects with mGluR Tier 1 variants (P < 0.035). There were no differences in the incidence of adverse events between placebo week and weeks on active drug. The trial is registered at https://clinicaltrials.gov/ct2/show/study/NCT02286817 .
Elia, Josephine; Ungal, Grace; Kao, Charlly; Ambrosini, Alexander; De Jesus-Rosario, Nilsa; Larsen, Lene; Chiavacci, Rosetta; Wang, Tiancheng; Kurian, Christine; Titchen, Kanani; Sykes, Brian; Hwang, Sharon; Kumar, Bhumi; Potts, Jacqueline; Davis, Joshua; Malatack, Jeffrey; Slattery, Emma; Moorthy, Ganesh; Zuppa, Athena; Weller, Andrew; Byrne, Enda; Li, Yun R.; Kraft, Walter K.; and Hakonarson, Hakon, "Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling." (2018). Department of Pediatrics Faculty Papers. Paper 75.
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This article has been peer reviewed. It is the author’s final published version in Nature Communications
Volume 9, Issue 1, December 2018, Article number 4.
The published version is available at https://doi.org/10.1038/s41467-017-02244-2. Copyright © Elia et al.