A Study of the Long Term Treatment of Rheumatoid Arthritis with Benorylate Suspension

Pavelka, Karel; Geirregat, R.; Vojtísĕk, O; Brémová, A

doi:10.1093/rheumatology/xii.suppl.48

Cited by 2 publications

(1 citation statement)

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“…Given the effect of uro-I on protein aggregation, we tested whether uro-I treatment initiates unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. We observed upregulation of BiP, consistent with UPR and ER stress 21 (Fig. 3C).…”

Section: Uro-i Impairs Osteoblastic Mineralization By Aggregating Matsupporting

confidence: 82%

Acitretin mitigates uroporphyrin-induced bone defects in congenital erythropoietic porphyria models

Cunha

Elenbaas

Maitra

et al. 2021

Preprint

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Congenital erythropoietic porphyria (CEP) is a rare genetic disorder leading to accumulation of uro/coproporphyrin-I in tissues due to inhibition of uroporphyrinogen-III synthase. Clinical manifestations of CEP include bone fragility, severe photosensitivity and photomutilation. Currently there is no specific treatment for CEP, except bone marrow transplantation, and there is an unmet need for treating this orphan disease. Fluorescent porphyrins cause protein aggregation, which led us to hypothesize that uroporphyrin-I accumulation leads to protein aggregation and CEP-related bone phenotype. We developed a zebrafish model that phenocopies features of CEP. As in human patients, uroporphyrin-I accumulated in the bones of zebrafish, leading to impaired bone development. Furthermore, in an osteoblast-like cell line, uroporphyrin-I decreased mineralization, aggregated bone matrix proteins, activated endoplasmic reticulum stress and disrupted autophagy. Using high-throughput drug screening, we identified acitretin, a second-generation retinoid, and showed that it reduced uroporphyrin-I accumulation and its deleterious effects on bones. Our findings provide a new CEP experimental model and a potential repurposed therapeutic.

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Section: Uro-i Impairs Osteoblastic Mineralization By Aggregating Matsupporting

confidence: 82%