Format

Send to

Choose Destination
EBioMedicine. 2018 Nov 28. pii: S2352-3964(18)30546-2. doi: 10.1016/j.ebiom.2018.11.042. [Epub ahead of print]

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

Author information

1
Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; Department of Experimental Pain Research, Medical Faculty Mannheim of Heidelberg University, Germany; Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University, 52074 Aachen, Germany.
2
Department of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
3
Department of Anesthesiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
4
Department of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; Department of Anesthesiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
5
Department of Neurology, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
6
Institute of Physiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
7
Icagen, Durham, NC 27703, USA.
8
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
9
Nanion Technologies GmbH, 80636 Munich, Germany.
10
Department of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
11
Department of Neurology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; Section of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
12
Department of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; Center of Rare Diseases Erlangen (ZSEER), Germany. Electronic address: beate.winner@fau.de.
13
Institute of Physiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany. Electronic address: alampert@ukaachen.de.

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.

KEYWORDS:

Human nociceptors; Microneurography; Multi-electrode-array; Patch-clamp; Personalized therapy; Small fiber neuropathy

PMID:
30503201
DOI:
10.1016/j.ebiom.2018.11.042
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center