Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy.
Animals
Cells, Cultured
Computational Biology
Disease Models, Animal
Drug Repositioning
/ methods
Gene Expression Profiling
/ methods
Harmine
/ pharmacology
Humans
Mice
Muscle, Skeletal
/ metabolism
Muscular Atrophy, Spinal
/ drug therapy
Neuromuscular Agents
/ pharmacology
Proteomics
/ methods
Survival of Motor Neuron 1 Protein
/ metabolism
Bioinformatics
Drug therapy
Genetic diseases
Muscle Biology
Neuroscience
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
08 07 2021
08 07 2021
Historique:
received:
09
03
2021
accepted:
17
05
2021
entrez:
8
7
2021
pubmed:
9
7
2021
medline:
12
2
2022
Statut:
epublish
Résumé
Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by loss of survival motor neuron (SMN) protein. While SMN restoration therapies are beneficial, they are not a cure. We aimed to identify potentially novel treatments to alleviate muscle pathology combining transcriptomics, proteomics, and perturbational data sets. This revealed potential drug candidates for repurposing in SMA. One of the candidates, harmine, was further investigated in cell and animal models, improving multiple disease phenotypes, including lifespan, weight, and key molecular networks in skeletal muscle. Our work highlights the potential of multiple and parallel data-driven approaches for the development of potentially novel treatments for use in combination with SMN restoration therapies.
Identifiants
pubmed: 34236053
pii: e149446
doi: 10.1172/jci.insight.149446
pmc: PMC8410072
doi:
pii:
Substances chimiques
Neuromuscular Agents
0
Survival of Motor Neuron 1 Protein
0
Harmine
4FHH5G48T7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105178803
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R025312/1
Pays : United Kingdom
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