Dodecyl creatine ester therapy: from promise to reality

Cell Mol Life Sci. 2024 Apr 17;81(1):186. doi: 10.1007/s00018-024-05218-y.

Abstract

Pathogenic variants in SLC6A8, the gene which encodes creatine transporter SLC6A8, prevent creatine uptake in the brain and result in a variable degree of intellectual disability, behavioral disorders (e.g., autism spectrum disorder), epilepsy, and severe speech and language delay. There are no treatments to improve neurodevelopmental outcomes for creatine transporter deficiency (CTD). In this spotlight, we summarize recent advances in innovative molecules to treat CTD, with a focus on dodecyl creatine ester, the most promising drug candidate.

Keywords: Biomarkers; Blood–brain barrier; Clinical trial; Cognitive functions; Creatine transporter deficiency; Nose-to-brain drug delivery; Proton MRS.

MeSH terms

  • Autism Spectrum Disorder*
  • Brain Diseases, Metabolic, Inborn* / drug therapy
  • Brain Diseases, Metabolic, Inborn* / genetics
  • Creatine / deficiency*
  • Creatine / genetics
  • Creatine / therapeutic use
  • Humans
  • Intellectual Disability* / genetics
  • Mental Retardation, X-Linked* / drug therapy
  • Mental Retardation, X-Linked* / genetics
  • Plasma Membrane Neurotransmitter Transport Proteins / deficiency*

Substances

  • Creatine
  • Plasma Membrane Neurotransmitter Transport Proteins

Supplementary concepts

  • Creatine deficiency, X-linked