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Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases

A “Leap-of-Faith” approach is used to treat patients with previously unknown ultrarare pathogenic mutations, often based on evidence from patients having dissimilar but more prevalent mutations. This uncertainty reflects the need to develop personalized prescreening platforms for these patients to a...

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Autores principales: Sequiera, Glen Lester, Srivastava, Abhay, Sareen, Niketa, Yan, Weiang, Alagarsamy, Keshav Narayan, Verma, Elika, Aghanoori, Mohamad Reza, Aliani, Michel, Kumar, Ashok, Fernyhough, Paul, Rockman-Greenberg, Cheryl, Dhingra, Sanjiv
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993122/
https://www.ncbi.nlm.nih.gov/pubmed/35394834
http://dx.doi.org/10.1126/sciadv.abl4370
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author Sequiera, Glen Lester
Srivastava, Abhay
Sareen, Niketa
Yan, Weiang
Alagarsamy, Keshav Narayan
Verma, Elika
Aghanoori, Mohamad Reza
Aliani, Michel
Kumar, Ashok
Fernyhough, Paul
Rockman-Greenberg, Cheryl
Dhingra, Sanjiv
author_facet Sequiera, Glen Lester
Srivastava, Abhay
Sareen, Niketa
Yan, Weiang
Alagarsamy, Keshav Narayan
Verma, Elika
Aghanoori, Mohamad Reza
Aliani, Michel
Kumar, Ashok
Fernyhough, Paul
Rockman-Greenberg, Cheryl
Dhingra, Sanjiv
author_sort Sequiera, Glen Lester
collection PubMed
description A “Leap-of-Faith” approach is used to treat patients with previously unknown ultrarare pathogenic mutations, often based on evidence from patients having dissimilar but more prevalent mutations. This uncertainty reflects the need to develop personalized prescreening platforms for these patients to assess drug efficacy before considering clinical trial enrollment. In this study, we report an 18-year-old patient with ultrarare Leigh-like syndrome. This patient had previously participated in two clinical trials with unfavorable responses. We established an induced pluripotent stem cell (iPSC)–based platform for this patient, and assessed the efficacy of a panel of drugs. The iPSC platform validated the safety and efficacy of the screened drugs. The efficacy of three of the screened drugs was also investigated in the patient. After 3 years of treatment, the drugs were effective in shifting the metabolic profile of this patient toward healthy control. Therefore, this personalized iPSC-based platform can act as a prescreening tool to help in decision-making with respect to patient’s participation in future clinical trials.
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spelling pubmed-89931222022-04-22 Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases Sequiera, Glen Lester Srivastava, Abhay Sareen, Niketa Yan, Weiang Alagarsamy, Keshav Narayan Verma, Elika Aghanoori, Mohamad Reza Aliani, Michel Kumar, Ashok Fernyhough, Paul Rockman-Greenberg, Cheryl Dhingra, Sanjiv Sci Adv Biomedicine and Life Sciences A “Leap-of-Faith” approach is used to treat patients with previously unknown ultrarare pathogenic mutations, often based on evidence from patients having dissimilar but more prevalent mutations. This uncertainty reflects the need to develop personalized prescreening platforms for these patients to assess drug efficacy before considering clinical trial enrollment. In this study, we report an 18-year-old patient with ultrarare Leigh-like syndrome. This patient had previously participated in two clinical trials with unfavorable responses. We established an induced pluripotent stem cell (iPSC)–based platform for this patient, and assessed the efficacy of a panel of drugs. The iPSC platform validated the safety and efficacy of the screened drugs. The efficacy of three of the screened drugs was also investigated in the patient. After 3 years of treatment, the drugs were effective in shifting the metabolic profile of this patient toward healthy control. Therefore, this personalized iPSC-based platform can act as a prescreening tool to help in decision-making with respect to patient’s participation in future clinical trials. American Association for the Advancement of Science 2022-04-08 /pmc/articles/PMC8993122/ /pubmed/35394834 http://dx.doi.org/10.1126/sciadv.abl4370 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Sequiera, Glen Lester
Srivastava, Abhay
Sareen, Niketa
Yan, Weiang
Alagarsamy, Keshav Narayan
Verma, Elika
Aghanoori, Mohamad Reza
Aliani, Michel
Kumar, Ashok
Fernyhough, Paul
Rockman-Greenberg, Cheryl
Dhingra, Sanjiv
Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases
title Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases
title_full Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases
title_fullStr Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases
title_full_unstemmed Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases
title_short Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases
title_sort development of ipsc-based clinical trial selection platform for patients with ultrarare diseases
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993122/
https://www.ncbi.nlm.nih.gov/pubmed/35394834
http://dx.doi.org/10.1126/sciadv.abl4370
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