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J01 Triheptanoin is associated with clinical stability and decreased caudate atrophy in huntington disease
  1. Fanny Mochel1,
  2. Aurélie Meneret1,
  3. Isaac Adanyeguh1,
  4. Camille Giron1,
  5. Elodie Hainque1,
  6. Marie-Pierre Luton1,
  7. Marie-Pierre Luton1,
  8. Mariana Atencio1,
  9. Milou Jacobs2,
  10. Fleur Veldkamp2,
  11. Emma Coppen2,
  12. Kasper van der Zwaan2,
  13. Eric Vicaut3,
  14. Raymund AC Roos2,
  15. Alexandra Durr1
  1. 1Paris Brain Institute, Paris, France
  2. 2LUMC dept Neurology, Leiden, the Netherlands
  3. 3APHP, Paris, France


Objective To assess the efficacy of triheptanoin, a medium chain triglyceride with an odd number of carbons that targets the Krebs cycle, on key brain imaging and clinical measures in HD.

Background We previously showed that energy deficit in HD is associated with increased substrate requirements for the Krebs cycle. Using brain MR spectroscopy, we then demonstrated that triheptanoin can restore a normal brain energetic profile in HD patients.

Methods We conducted a 6-month randomized controlled bi-centric trial (Paris and Leiden) called TRIHEP3 (NCT02453061), comparing triheptanoin 1g/kg/day vs placebo in 100 patients (ratio 1/1) at an early stage of HD, followed by a 6-month open label phase. Patients could then opt for a one-year extension study. To compare triheptanoin versus placebo over one year, we used the placebo arm of a one-year randomized controlled trial (NCT02336633), conducted in parallel with identical methods, in HD patients with similar clinical characteristics (age, UHDRS-TMS, CAG).

Results 86 patients completed the one-year TRIHEP3 study and 42 completed the consecutive 12-month extension. Triheptanoin was well tolerated. We saw no difference in cBSI at 6 months between triheptanoin and placebo. TMS at 12 months tended to stabilize in patients treated with triheptanoin for one year (mean 0.6 ± 5.1) compared to patients treated for 6 months (2.5 ± 4.5) (p= 0.072), with a significant difference between 6 and 12 months (-0.7 ± 3.9 vs 1.9 ± 4.7, p= 0.024). Diffusion tensor imaging showed improved fiber trophicity at 24 months in both groups. Compared to the external placebo control group, at one year, TMS confirmed clinical stability in patients treated with triheptanoin (2.6 ± 4.6 vs 0.6 ± 5.1, p= 0.057) and caudate atrophy was significantly less (-3% vs -6.7% compared to baseline, p< 0.001) (figure 1).

Conclusion These results showed that treatment with triheptanoin was associated with clinical stability and decreased caudate atrophy in HD.

  • triheptanoin
  • krebs cycle
  • clinical trial
  • caudate atrophy
  • diffusion tensor imaging

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