Drug Repurposing in Rare Diseases: An Integrative Study of Drug Screening and Transcriptomic Analysis in Nephropathic Cystinosis.
Amino Acid Transport Systems, Neutral
/ genetics
Cells, Cultured
Computational Biology
/ methods
Cystinosis
/ drug therapy
Drug Evaluation, Preclinical
/ methods
Drug Repositioning
Humans
Kidney Diseases
/ drug therapy
Kidney Tubules, Proximal
/ drug effects
Metabolic Networks and Pathways
Rare Diseases
/ drug therapy
Transcriptome
cystinosis
drug repositioning
high content screening
high throughput screening
transcriptome
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
27 Nov 2021
27 Nov 2021
Historique:
received:
18
10
2021
revised:
22
11
2021
accepted:
24
11
2021
entrez:
10
12
2021
pubmed:
11
12
2021
medline:
27
1
2022
Statut:
epublish
Résumé
Diagnosis and cure for rare diseases represent a great challenge for the scientific community who often comes up against the complexity and heterogeneity of clinical picture associated to a high cost and time-consuming drug development processes. Here we show a drug repurposing strategy applied to nephropathic cystinosis, a rare inherited disorder belonging to the lysosomal storage diseases. This approach consists in combining mechanism-based and cell-based screenings, coupled with an affordable computational analysis, which could result very useful to predict therapeutic responses at both molecular and system levels. Then, we identified potential drugs and metabolic pathways relevant for the pathophysiology of nephropathic cystinosis by comparing gene-expression signature of drugs that share common mechanisms of action or that involve similar pathways with the disease gene-expression signature achieved with RNA-seq.
Identifiants
pubmed: 34884638
pii: ijms222312829
doi: 10.3390/ijms222312829
pmc: PMC8657658
pii:
doi:
Substances chimiques
Amino Acid Transport Systems, Neutral
0
CTNS protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cystinosis Research Foundation
ID : CRFS-2011
Organisme : Telethon Foundation
ID : TGM11CB1
Organisme : Italian Association for Cancer Research
ID : IG2013_14761
Organisme : Governo Italiano
ID : 5x1000
Organisme : Governo Italiano
ID : Ricerca Corrente
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