1. Drug Repurposing in Rare Diseases: An Integrative Study of Drug Screening and Transcriptomic Analysis in Nephropathic Cystinosis
- Author
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Francesco Emma, Anna Pastore, Ester De Leo, Francesco Bellomo, Maria Antonietta De Matteis, Laura Giaquinto, Gianna Di Giovamberardino, Diego L. Medina, Laura Rita Rega, Anna Taranta, Sandro Montefusco, Diego di Bernardo, Bellomo, F., De Leo, E., Taranta, A., Giaquinto, L., Di Giovamberardino, G., Montefusco, S., Rega, L. R., Pastore, A., Medina, D. L., Di Bernardo, D., De Matteis, M. A., and Emma, F.
- Subjects
Drug ,QH301-705.5 ,media_common.quotation_subject ,Cystinosis ,Drug Evaluation, Preclinical ,Computational biology ,Disease ,Catalysis ,Article ,Inorganic Chemistry ,Kidney Tubules, Proximal ,cystinosis ,drug repositioning ,high throughput screening ,transcriptome ,high content screening ,Rare Diseases ,Nephropathic Cystinosis ,medicine ,Humans ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,Cells, Cultured ,media_common ,Mechanism (biology) ,business.industry ,Cystinosi ,Organic Chemistry ,Drug Repositioning ,Computational Biology ,General Medicine ,medicine.disease ,Computer Science Applications ,Drug repositioning ,Chemistry ,Amino Acid Transport Systems, Neutral ,Drug development ,High-content screening ,Kidney Diseases ,business ,Transcriptome ,Metabolic Networks and Pathways - Abstract
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.
- Published
- 2021