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A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS.

Abstract：

:Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease, characterized by motor neuron (MN) death, for which there are no truly effective treatments. Here, we describe a new small molecule survival screen carried out using MNs from both wild-type and mutant SOD1 mouse embryonic stem cells. Among the hits we found, kenpaullone had a particularly impressive ability to prolong the healthy survival of both types of MNs that can be attributed to its dual inhibition of GSK-3 and HGK kinases. Furthermore, kenpaullone also strongly improved the survival of human MNs derived from ALS-patient-induced pluripotent stem cells and was more active than either of two compounds, olesoxime and dexpramipexole, that recently failed in ALS clinical trials. Our studies demonstrate the value of a stem cell approach to drug discovery and point to a new paradigm for identification and preclinical testing of future ALS therapeutics.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Yang YM,Gupta SK,Kim KJ,Powers BE,Cerqueira A,Wainger BJ,Ngo HD,Rosowski KA,Schein PA,Ackeifi CA,Arvanites AC,Davidow LS,Woolf CJ,Rubin LL

doi

10.1016/j.stem.2013.04.003

subject

Has Abstract

pub_date

2013-06-06 00:00:00

pages

713-26

issue

6

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(13)00139-2

journal_volume

12

pub_type

杂志文章

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