title: Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency.
abstract: OBJECTIVE
  On the basis of our previous work with triheptanoin, which provides key substrates to the Krebs cycle in the brain, we wished to assess its therapeutic effect in patients with glucose transporter type 1 deficiency syndrome (GLUT1-DS) who objected to or did not tolerate ketogenic diets.
  
  
  METHODS
  We performed an open-label pilot study with three phases of 2 months each (baseline, treatment and withdrawal) in eight patients with GLUT1-DS (7-47 years old) with non-epileptic paroxysmal manifestations. We used a comprehensive patient diary to record motor and non-motor paroxysmal events. Functional (31)P-NMR spectroscopy was performed to quantify phosphocreatine (PCr) and inorganic phosphate (Pi) within the occipital cortex during (activation) and after (recovery) a visual stimulus.
  
  
  RESULTS
  Patients with GLUT1-DS experienced a mean of 30.8 (± 27.7) paroxysmal manifestations (52% motor events) at baseline that dropped to 2.8 (± 2.9, 76% motor events) during the treatment phase (p = 0.028). After withdrawal, paroxysmal manifestations recurred with a mean of 24.2 (± 21.9, 52% motor events; p = 0.043). Furthermore, brain energy metabolism normalised with triheptanoin, that is, increased Pi/PCr ratio during brain activation compared to the recovery phase (p = 0.021), and deteriorated when triheptanoin was withdrawn.
  
  
  CONCLUSIONS
  Treatment with triheptanoin resulted in a 90% clinical improvement in non-epileptic paroxysmal manifestations and a normalised brain bioenergetics profile in patients with GLUT1-DS.
  
  
  BACKGROUND
  NCT02014883.
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France Department of Genetics, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Mochel
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France Department of Neurology, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Hainque
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France Department of Neuropediatrics, AP-HP, Robert Debré University Hospital, Paris, France.
authors.forename: Domitille
authors.initials: D
authors.lastname: Gras
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
authors.forename: Isaac M
authors.initials: IM
authors.lastname: Adanyeguh
authors.affiliation: Department of Dietetics, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: Samantha
authors.initials: S
authors.lastname: Caillet
authors.affiliation: Department of Neuropediatrics, AP-HP, Armand Trousseau University Hospital, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Héron
authors.affiliation: Department of Neuropediatrics, Gui de Chauliac Hospital, Montpellier, France INSERM, U-1051, Institute of Neuroscience, Montpellier, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Roubertie
authors.affiliation: Department of Neurology, AP-HM, La Timone University Hospital, Marseille, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Kaphan
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France Center for NeuroImaging Research (CENIR), Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Valabregue
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
authors.forename: Daisy
authors.initials: D
authors.lastname: Rinaldi
authors.affiliation: Biochemistry and Genetic Laboratory, AP-HP, Bichat-Claude Bernard Hospital, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Vuillaumier
authors.affiliation: Baylor Research Institute, Institute of Metabolic Disease, Dallas, Texas, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.affiliation: Metabolic Biochemistry Lab, AP-HP, Necker University Hospital, Paris, France University Paris Descartes, Paris, France.
authors.forename: Chris
authors.initials: C
authors.lastname: Ottolenghi
authors.affiliation: Neuromuscular Physiology and Evaluation Lab, Institute of Myology, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
authors.affiliation: Service of Clinical Research and Databases, Institute of Myology, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Servais
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France Department of Neurology, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roze
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002819:Chorea / Q000188:drug therapy* / Q000235:genetics*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D059907:Functional Neuroimaging; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010865:Pilot Projects; D014280:Triglycerides / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D051272:Glucose Transporter Type 1; D010710:Phosphates; C495677:SLC2A1 protein, human; D014280:Triglycerides; D010725:Phosphocreatine; C531010:triheptanoin
keywords: METABOLIC DISEASE; MOVEMENT DISORDERS