Intrathecal magnesium delivery for Mg++-insensitive NMDA receptor activity due to GRIN1 mutation

Sara A. Lewis, Sheetal Shetty, Sean Gamble, Jennifer Heim, Ningning Zhao, Gideon Stitt, Matthew Pankratz, Tara Mangum, Iris Marku, Robert B. Rosenberg, Angus A. Wilfong, Michael C. Fahey, Sukhan Kim, Scott J. Myers, Brian Appavu, Michael C. Kruer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Mutations in the NMDA receptor are known to disrupt glutamatergic signaling crucial for early neurodevelopment, often leading to severe global developmental delay/intellectual disability, epileptic encephalopathy, and cerebral palsy phenotypes. Both seizures and movement disorders can be highly treatment-refractory. Results: We describe a targeted ABA n-of-1 treatment trial with intrathecal MgSO4, rationally designed based on the electrophysiologic properties of this gain of function mutation in the GRIN1 NMDA subunit. Conclusion: Although the invasive nature of the trial necessitated a short-term, non-randomized, unblinded intervention, quantitative longitudinal neurophysiologic monitoring indicated benefit, providing class II evidence in support of intrathecal MgSO4 for select forms of GRIN disorders.

Original languageEnglish (US)
Article number225
JournalOrphanet Journal of Rare Diseases
Issue number1
StatePublished - Dec 2023


  • /Terms epileptic encephalopathy
  • Cerebral palsy
  • Dystonia
  • GRIN Disorders
  • N-of-1 treatment trial
  • Neurodevelopmental Disorders
  • NMDA receptor
  • Precision Medicine

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)


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