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The use of human neurons for novel drug discovery in dementia research

The use of human neurons for novel drug discovery in dementia research
The use of human neurons for novel drug discovery in dementia research
Although many disease models exist for neurodegenerative disease, the translation of basic research findings to clinic is very limited. Studies using freshly resected human brain tissue, commonly discarded from neurosurgical procedures, should complement on-going work using stem cell-derived human neurons and glia thus increasing the likelihood of success in clinical trials.

Areas covered: Herein, the authors discuss key issues in the lack of translation from basic research to clinic. They also review the evidence that human neurons, both freshly resected brain tissue and stem cell-derived neurons, such as induced pluripotent stem cells (iPSCs), can be used for analysis of physiological and molecular mechanisms in health and disease. Furthermore, the authors compare and contrast studies using live human brain tissue and studies using induced human stem cell-derived neuron models. Using an example from the area of neurodegeneration, the authors suggest that replicating elements of research findings from animals and stem cell models in resected human brain tissue would strengthen our understanding of disease mechanisms and the therapeutic strategies and aid translation.

Expert opinion: The use of human brain tissue alongside iPSC-derived neural models can validate molecular mechanisms identified in rodent disease models and strengthen their relevance to humans. If drug target engagement and mechanism of cellular action can be validated in human brain tissue, this will increase the success rate in clinical research. The combined use of resected human brain tissue, alongside iPSC-derived neural models, could be considered a standard step in pre-clinical research and help to bridge the gap to clinical trials.
human, neurons, brain, disease, mouse models, translation
1746-0441
1-35
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Willaime-Morawek, Sandrine
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Bulters, Diedrik
1d6ebbd0-eee4-47fe-8602-5b4ba22f2db0
Mudher, Amrit
ce0ccb35-ac49-4b6c-92b4-8dd5e78ac119
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Willaime-Morawek, Sandrine
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Bulters, Diedrik
1d6ebbd0-eee4-47fe-8602-5b4ba22f2db0
Mudher, Amrit
ce0ccb35-ac49-4b6c-92b4-8dd5e78ac119

Vargas-Caballero, Mariana, Willaime-Morawek, Sandrine, Gomez-Nicola, Diego, Perry, V. Hugh, Bulters, Diedrik and Mudher, Amrit (2016) The use of human neurons for novel drug discovery in dementia research. Expert Opinion on Drug Discovery, 1-35. (doi:10.1517/17460441.2016.1154528). (PMID:26878555)

Record type: Review

Abstract

Although many disease models exist for neurodegenerative disease, the translation of basic research findings to clinic is very limited. Studies using freshly resected human brain tissue, commonly discarded from neurosurgical procedures, should complement on-going work using stem cell-derived human neurons and glia thus increasing the likelihood of success in clinical trials.

Areas covered: Herein, the authors discuss key issues in the lack of translation from basic research to clinic. They also review the evidence that human neurons, both freshly resected brain tissue and stem cell-derived neurons, such as induced pluripotent stem cells (iPSCs), can be used for analysis of physiological and molecular mechanisms in health and disease. Furthermore, the authors compare and contrast studies using live human brain tissue and studies using induced human stem cell-derived neuron models. Using an example from the area of neurodegeneration, the authors suggest that replicating elements of research findings from animals and stem cell models in resected human brain tissue would strengthen our understanding of disease mechanisms and the therapeutic strategies and aid translation.

Expert opinion: The use of human brain tissue alongside iPSC-derived neural models can validate molecular mechanisms identified in rodent disease models and strengthen their relevance to humans. If drug target engagement and mechanism of cellular action can be validated in human brain tissue, this will increase the success rate in clinical research. The combined use of resected human brain tissue, alongside iPSC-derived neural models, could be considered a standard step in pre-clinical research and help to bridge the gap to clinical trials.

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More information

e-pub ahead of print date: 11 February 2016
Published date: 15 February 2016
Keywords: human, neurons, brain, disease, mouse models, translation
Organisations: Biomedicine

Identifiers

Local EPrints ID: 388178
URI: https://eprints.soton.ac.uk/id/eprint/388178
ISSN: 1746-0441
PURE UUID: be38bda6-4cf5-415a-8b3f-8af9912d7edb
ORCID for Mariana Vargas-Caballero: ORCID iD orcid.org/0000-0003-2326-4001
ORCID for Sandrine Willaime-Morawek: ORCID iD orcid.org/0000-0002-1121-6419
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 19 Feb 2016 14:52
Last modified: 06 Jun 2018 12:37

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