Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors
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 C...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-01-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418305462 |
| _version_ | 1818083529796354048 |
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| author | Barbara Namer Diana Schmidt Esther Eberhardt Michele Maroni Eva Dorfmeister Inge Petter Kleggetveit Luisa Kaluza Jannis Meents Aaron Gerlach Zhixin Lin Andreas Winterpacht Elena Dragicevic Zacharias Kohl Jürgen Schüttler Ingo Kurth Torhild Warncke Ellen Jorum Beate Winner Angelika Lampert |
| author_facet | Barbara Namer Diana Schmidt Esther Eberhardt Michele Maroni Eva Dorfmeister Inge Petter Kleggetveit Luisa Kaluza Jannis Meents Aaron Gerlach Zhixin Lin Andreas Winterpacht Elena Dragicevic Zacharias Kohl Jürgen Schüttler Ingo Kurth Torhild Warncke Ellen Jorum Beate Winner Angelika Lampert |
| author_sort | Barbara Namer |
| collection | DOAJ |
| description | 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: Personalized therapy, Human nociceptors, Small fiber neuropathy, Microneurography, Patch-clamp, Multi-electrode-array |
| first_indexed | 2024-12-10T19:39:27Z |
| format | Article |
| id | doaj.art-91146ae9315e46b38077f020b2157149 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-10T19:39:27Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-91146ae9315e46b38077f020b21571492022-12-22T01:36:01ZengElsevierEBioMedicine2352-39642019-01-0139401408Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptorsBarbara Namer0Diana Schmidt1Esther Eberhardt2Michele Maroni3Eva Dorfmeister4Inge Petter Kleggetveit5Luisa Kaluza6Jannis Meents7Aaron Gerlach8Zhixin Lin9Andreas Winterpacht10Elena Dragicevic11Zacharias Kohl12Jürgen Schüttler13Ingo Kurth14Torhild Warncke15Ellen Jorum16Beate Winner17Angelika Lampert18Institute 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, GermanyDepartment of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Anesthesiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; Department of Anesthesiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Neurology, Oslo University Hospital-Rikshospitalet, Oslo, NorwayInstitute of Physiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyInstitute of Physiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyIcagen, Durham, NC 27703, USAIcagen, Durham, NC 27703, USAInstitute of Human Genetics, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyNanion Technologies GmbH, 80636 Munich, GermanyDepartment of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Anesthesiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Human Genetics, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Anesthesiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Neurology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; Section of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital-Rikshospitalet, Oslo, NorwayDepartment of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; Center of Rare Diseases Erlangen (ZSEER), Germany; Correspondence to: B. Winner, Glückstr. 6, 91054 Erlagen, Germany.Institute of Physiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany; Correspondence to: A. Lampert, Pauwelsstr. 30, 52074 Aachen, Germany.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: Personalized therapy, Human nociceptors, Small fiber neuropathy, Microneurography, Patch-clamp, Multi-electrode-arrayhttp://www.sciencedirect.com/science/article/pii/S2352396418305462 |
| spellingShingle | Barbara Namer Diana Schmidt Esther Eberhardt Michele Maroni Eva Dorfmeister Inge Petter Kleggetveit Luisa Kaluza Jannis Meents Aaron Gerlach Zhixin Lin Andreas Winterpacht Elena Dragicevic Zacharias Kohl Jürgen Schüttler Ingo Kurth Torhild Warncke Ellen Jorum Beate Winner Angelika Lampert Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors EBioMedicine |
| title | Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors |
| title_full | Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors |
| title_fullStr | Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors |
| title_full_unstemmed | Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors |
| title_short | Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors |
| title_sort | pain relief in a neuropathy patient by lacosamide proof of principle of clinical translation from patient specific ips cell derived nociceptors |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418305462 |
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