2. Academic Validation
  3. Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling

Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling

  • Nat Commun. 2018 Jan 16;9(1):4. doi: 10.1038/s41467-017-02244-2.
Josephine Elia 1 2 3,  Grace Ungal 4,  Charlly Kao 5,  Alexander Ambrosini 6,  Nilsa De Jesus-Rosario 7,  Lene Larsen 7,  Rosetta Chiavacci 5,  Tiancheng Wang 5,  Christine Kurian 8,  Kanani Titchen 9 8,  Brian Sykes 9 8,  Sharon Hwang 9 8,  Bhumi Kumar 9 8,  Jacqueline Potts 8,  Joshua Davis 9 8,  Jeffrey Malatack 9,  Emma Slattery 8,  Ganesh Moorthy 10,  Athena Zuppa 10,  Andrew Weller 7,  Enda Byrne 5,  Yun R Li 5 11,  Walter K Kraft 8,  Hakon Hakonarson 5 10 12
Affiliations

Affiliations

  • 1 Nemours, du Pont Hospital for Children, Wilmington, 19803, DE, USA. Josephine.Elia@nemours.org.
  • 2 Department of Pediatrics Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, 19107, PA, USA. Josephine.Elia@nemours.org.
  • 3 Department of Psychiatry Sidney Kimmel Medical College of Thomas Jefferson University, 19107, Philadelphia, USA. Josephine.Elia@nemours.org.
  • 4 Drexel University College of Medicine, Philadelphia, 19129, PA, USA.
  • 5 The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 19104, PA, USA.
  • 6 University of Pennsylvania, Philadelphia, 19104, PA, USA.
  • 7 Department of Psychiatry Sidney Kimmel Medical College of Thomas Jefferson University, 19107, Philadelphia, USA.
  • 8 Department of Pediatrics Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, 19107, PA, USA.
  • 9 Nemours, du Pont Hospital for Children, Wilmington, 19803, DE, USA.
  • 10 Department of Pediatrics Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, PA, USA.
  • 11 Department of Radiation Oncology, Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, 94143, CA, USA.
  • 12 Divisions of Human Genetics and Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, 19104, PA, USA.
PMID: 29339723 DOI: 10.1038/s41467-017-02244-2
Abstract

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 .

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