Patient-derived neuronal models for pharmacogenetic pain treatment of sodium channelopathies

Julie Labau

Research output: ThesisDoctoral ThesisInternal

Abstract

Chronic pain affects nearly 1 in 4 individuals worldwide. Despite its global spread, patients systematically report lack of efficacy and severe side effects from available treatments, leading to years of trial-and-error management for little to no improvement. Lacosamide, originally developed for epilepsy, was found to reduce pain in a sub-group of patients. This research shows that some mutations in genes involved with the transmission of pain signals can alter drug effects. Another discovery was that one particular mutation, which completely prevented pain relief in patients, was responsible for linking the lacosamide molecules to their receptors, which then block the pain signal. The identification of such mutations can predict how a patient will respond to the drug before even receiving it. Nowadays, the patient’s own cells can be tested against different drugs. Stem cells can be obtained from a skin sample and turned into neurons. However, they are imperfect copies of the patient’s actual neurons. This thesis shows ways to improve cell quality, notably by injecting them into the rat nervous system and by using electrical stimulation.
Original languageEnglish
Awarding Institution
  • Maastricht University
Supervisors/Advisors
  • Smeets, Bert, Supervisor
  • Faber, Karin, Supervisor
  • Dib-Hajj, S.D., Co-Supervisor, External person
  • Waxman, S.G., Co-Supervisor, External person
Award date21 Apr 2022
DOIs
Publication statusPublished - 2022

Keywords

  • pain
  • lacosamide
  • stem cells
  • sodium channels

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