Dataset Information

Advances in Patient-Specific Induced Pluripotent Stem Cells Shed Light on Drug Discovery for Amyotrophic Lateral Sclerosis.

ABSTRACT: Induced pluripotent stem cells (iPSCs), which are generated through reprogramming adult somatic cells by expressing specific transcription factors, can differentiate into derivatives of the three embryonic germ layers and accelerate rapid advances in stem cell research. Neurological diseases such as amyotrophic lateral sclerosis (ALS) have benefited enormously from iPSC technology. This approach can be particularly important for creating iPSCs from patients with familial or sporadic forms of ALS. Motor neurons differentiated from the ALS-patient-derived iPSC can help to determine the relationship between cellular phenotype and genotype. Patient-derived iPSCs facilitate the development of new drugs and/or drug screening for ALS treatment and allow the exploration of the possible mechanism of ALS disease. In this article, we reviewed ALS-patient-specific iPSCs with various genetic mutations, progress in drug development for ALS disease, functional assays showing the differentiation of iPSCs into mature motor neurons, and promising biomarkers in ALS patients for the evaluation of drug candidates.

SUBMITTER: Lee JH

PROVIDER: S-EPMC6168987 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Advances in Patient-Specific Induced Pluripotent Stem Cells Shed Light on Drug Discovery for Amyotrophic Lateral Sclerosis.

Lee Jui-Hao JH Liu Jen-Wei JW Lin Shinn-Zong SZ Harn Horng-Jyh HJ Chiou Tzyy-Wen TW

Cell transplantation 20180723 9

Induced pluripotent stem cells (iPSCs), which are generated through reprogramming adult somatic cells by expressing specific transcription factors, can differentiate into derivatives of the three embryonic germ layers and accelerate rapid advances in stem cell research. Neurological diseases such as amyotrophic lateral sclerosis (ALS) have benefited enormously from iPSC technology. This approach can be particularly important for creating iPSCs from patients with familial or sporadic forms of ALS ...[more]

PMID: 30033758

Similar Datasets

Project description:IntroductionAmyotrophic lateral sclerosis (ALS) is a progressive and severe neurodegenerative disease caused by motor neuron death. There have as yet been no fundamental curative medicines, and the development of a medicine for ALS is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified an Src/c-Abl inhibitor, bosutinib, as a candidate molecular targeted therapy for ALS. The objectives of this study are to evaluate the safety and tolerability of bosutinib for the treatment of patients with ALS and to explore the efficacy of bosutinib on ALS. This study is the first clinical trial of administered bosutinib for patients with ALS.Methods and analysisAn open-label, multicentre phase I dose escalation study has been designed. The study consists of a 12-week observation period, a 1-week transitional period, a 12-week study treatment period and a 4-week follow-up period. After completion of the transitional period, subjects whose total ALS Functional Rating Scale-Revised (ALSFRS-R) score decreased by 1-3 points during the 12-week observation period receive bosutinib for 12 weeks. Three to six patients with ALS are enrolled in each of the four bosutinib dose levels (100, 200, 300 or 400 mg/day) to evaluate the safety and tolerability under a 3+3 dose escalation study design. Dose escalation and maximum tolerated dose are determined by the safety assessment committee comprising oncologists/haematologists and neurologists based on the incidence of dose-limiting toxicity in the first 4 weeks of the treatment at each dose level. A recommended phase II dose is determined by the safety assessment committee on completion of the 12-week study treatment in all subjects at all dose levels. The efficacy of bosutinib is also evaluated exploratorily using ALS clinical scores and biomarkers.Ethics and disseminationThis study received full ethical approval from the institutional review board of each participating site. The findings of the study will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberUMIN000036295; Pre-results, JMA-IIA00419; Pre-results.

Dataset Information

Advances in Patient-Specific Induced Pluripotent Stem Cells Shed Light on Drug Discovery for Amyotrophic Lateral Sclerosis.

Publications

Advances in Patient-Specific Induced Pluripotent Stem Cells Shed Light on Drug Discovery for Amyotrophic Lateral Sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets