Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors

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Details zur Publikation

Autorinnen und Autoren: Namer B, Schmidt D, Eberhardt E, Maroni M, Dorfmeister E, Kleggetveit IP, Kaluza L, Meents J, Gerlach A, Lin Z, Winterpacht A, Dragicevic E, Kohl Z, Schüttler J, Kurth I, Warncke T, Jorum E, Winner B, Lampert A
Zeitschrift: EBioMedicine
Jahr der Veröffentlichung: 2018
ISSN: 2352-3964


Abstract

BACKGROUND: Small fiber neuropathy (SFN) is a severe and disabling chronic pain syndrome with no causal and limited symptomatic treatment options. Mechanistically based individual treatment is not available. We report an in-vitro predicted individualized treatment success in one therapy-refractory Caucasian patient suffering from SFN for over ten years.
METHODS: Intrinsic excitability of human induced pluripotent stem cell (iPSC) derived nociceptors from this patient and respective controls were recorded on multi-electrode (MEA) arrays, in the presence and absence of lacosamide. The patient's pain ratings were assessed by a visual analogue scale (10: worst pain, 0: no pain) and treatment effect was objectified by microneurography recordings of the patient's single nerve C-fibers.
FINDINGS: We identified patient-specific changes in iPSC-derived nociceptor excitability in MEA recordings, which were reverted by the FDA-approved compound lacosamide in vitro. Using this drug for individualized treatment of this patient, the patient's pain ratings decreased from 7.5 to 1.5. Consistent with the pain relief reported by the patient, microneurography recordings of the patient's single nerve fibers mirrored a reduced spontaneous nociceptor (C-fiber) activity in the patient during lacosamide treatment. Microneurography recordings yielded an objective measurement of altered peripheral nociceptor activity following treatment.
INTERPRETATION: Thus, we are here presenting one example of successful patient specific precision medicine using iPSC technology and individualized therapeutic treatment based on patient-derived sensory neurons.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Eberhardt, Esther Dr. med.
Winner, Beate Prof. Dr.
Anästhesiologische Klinik
Humangenetisches Institut
Kohl, Zacharias PD Dr.
Medizinische Fakultät
Maroni, Michele
Anästhesiologische Klinik
Namer, Barbara PD Dr.
Medizinische Fakultät
Schmidt, Diana
Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe III
Schüttler, Jürgen Prof. Dr.
Lehrstuhl für Anästhesiologie
Winterpacht, Andreas Prof. Dr.
Professur für Humangenetik


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Zitierweisen

APA:
Namer, B., Schmidt, D., Eberhardt, E., Maroni, M., Dorfmeister, E., Kleggetveit, I.P.,... Lampert, A. (2018). Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors. EBioMedicine. https://dx.doi.org/10.1016/j.ebiom.2018.11.042

MLA:
Namer, Barbara, et al. "Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors." EBioMedicine (2018).

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Zuletzt aktualisiert 2019-21-01 um 09:23