Journal article
Improving the Pharmacological Properties of Ciclopirox for Its Use in Congenital Erythropoietic Porphyria
Journal of personalized medicine, v 11(6), 485
28 May 2021
PMID: 34071291
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Congenital erythropoietic porphyria (CEP), also known as Gunther's disease, results from a deficient activity in the fourth enzyme, uroporphyrinogen III synthase (UROIIIS), of the heme pathway. Ciclopirox (CPX) is an off-label drug, topically prescribed as an antifungal. It has been recently shown that it also acts as a pharmacological chaperone in CEP, presenting a specific activity in deleterious mutations in UROIIIS. Despite CPX is active at subtoxic concentrations, acute gastrointestinal (GI) toxicity was found due to the precipitation in the stomach of the active compound and subsequent accumulation in the intestine. To increase its systemic availability, we carried out pharmacokinetic (PK) and pharmacodynamic (PD) studies using alternative formulations for CPX. Such strategy effectively suppressed GI toxicity in WT mice and in a mouse model of the CEP disease (UROIIISP248Q/P248Q). In terms of activity, phosphorylation of CPX yielded good results in CEP cellular models but showed limited activity when administered to the CEP mouse model. These results highlight the need of a proper formulation for pharmacological chaperones used in the treatment of rare diseases.
Metrics
1 Record Views
Details
- Title
- Improving the Pharmacological Properties of Ciclopirox for Its Use in Congenital Erythropoietic Porphyria
- Creators
- Ganeko Bernardo-Seisdedos - United States Department of EducationJorge M. Charco - United States Department of EducationItxaso SanJuan - CIC bioGUNESandra Garcia-Martinez - United States Department of EducationPedro Urquiza - CIC bioGUNEHasier Erana - United States Department of EducationJoaquin Castilla - IkerbasqueOscar Millet - CIC bioGUNE
- Publication Details
- Journal of personalized medicine, v 11(6), 485
- Publisher
- Mdpi
- Grant note
- Department of Industry, Tourism and Trade of the Government of the Autonomous Community of the Basque Country SEV-2016-0644 / Severo Ochoa Excellence Accreditation from MCIU RTI2018-101269-B-I00 / Agencia Estatal de Investigacion (Spain); Spanish Government
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000667411800001
- Scopus ID
- 2-s2.0-85107868187
- Other Identifier
- 991022197351304721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
Source: SDGs in the Output
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Health Care Sciences & Services