A prostaglandin D2 metabolite is elevated in the urine of Duchenne muscular dystrophy patients and increases further from 8years old

Nagao, Taku; Takeuchi, Atsuko; Kakiuchi, R.; Lee, Tomoko; Yagi, Minoru; Awano, Hiroyuki; Iijima, Kazumoto; Takeshima, Yasuhiro; Urade, Yoshihiro; Matsuo, Masafumi

doi:10.1016/j.cca.2013.03.031

Cited by 33 publications

(27 citation statements)

References 36 publications

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“…We are therefore planning a next study to investigate the long‐term dosing benefits of TAS‐205 in a greater DMD patient population. Furthermore, it has been previously reported that steroid therapy does not alter levels of tPGDM/Cre in DMD patients even though steroid treatment has been shown to inhibit prostaglandin biosynthesis . Therefore, the interaction between steroid treatment and the selective HPGDS inhibitor, TAS‐205, requires more consideration.…”

Section: Discussionmentioning

confidence: 99%

“…Urinary tPGDM is the primary metabolite of PGD 2 in both mice and humans, and therefore, can be used as a marker of PGD 2 production in vivo . It has been reported that the urinary excretion of tPGDM increased in DMD patients compared with age‐matched healthy subjects or children with other diseases . Therefore, PGD 2 ‐mediated inflammation is suggested to be involved in the pathology of DMD, and inhibition of PGD 2 production via HPGDS inhibition may be an effective therapeutic modality.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16] Clinical research on PGD 2 activity shows that HPGDS is expressed in myonecrotic areas in DMD patients and that PGD 2mediated inflammation is associated with the development of muscle necrosis over time. 17 In a DMD mouse model, a PGD 2 inhibitor decreased the excretion of the PGD 2 urinary metabolite, tetranor-PGDM (tPGDM), and inhibited myonecrosis. 16 Urinary tPGDM is the primary metabolite of PGD 2 in both mice and humans, and therefore, can be used as a marker of PGD 2 production in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy

Komaki

Maegaki

Matsumura

et al. 2020

Ann Clin Transl Neurol

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Objective Duchenne muscular dystrophy (DMD) is a progressive muscular disease characterized by chronic cycles of inflammatory and necrotic processes. Prostaglandin D2 (PGD2) is produced by hematopoietic PGD synthase (HPGDS), which is pathologically implicated in muscle necrosis. This randomized, double‐blind, placebo‐controlled early phase 2 study (NCT02752048) aimed to assess the efficacy and safety of the novel selective HPGDS inhibitor, TAS‐205, with exploratory measures in male DMD patients aged ≥5 years. Methods Patients were randomized 1:1:1 to receive low‐dose TAS‐205 (6.67–13.33 mg/kg/dose), high‐dose TAS‐205 (13.33–26.67 mg/kg/dose), or placebo. The primary endpoint was the change from baseline in a 6‐minute walk distance (6MWD) at Week 24. Results Thirty‐six patients were enrolled, of whom 35 patients were analysed for safety. The mean (standard error) changes from baseline to Week 24 in 6MWD were −17.0 (17.6) m in the placebo group (n = 10), −3.5 (20.3) m in the TAS‐205 low‐dose group (n = 11), and −7.5 (11.2) m in the TAS‐205 high‐dose group (n = 11). The mean (95% confidence interval) difference from the placebo group was 13.5 (−43.3 to 70.2) m in the TAS‐205 low‐dose group and 9.5 (−33.3 to 52.4) m in the TAS‐205 high‐dose group. No obvious differences were observed in the incidences of adverse events between treatment groups. No adverse drug reactions specific to TAS‐205 treatment were observed. Interpretation The HPGDS inhibitor TAS‐205 showed a favorable safety profile in DMD patients. Further research is required to examine the effectiveness of TAS‐205 in a larger trial.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy

Komaki

Maegaki

Matsumura

et al. 2020

Ann Clin Transl Neurol

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“…All metabolites were confirmed by MS/MS spectra and fragments found were compared with the literature and databases such as METLIN, Human Metabolome Database and Mass Bank.…”

Section: Resultsmentioning

confidence: 99%

A discovery‐driven approach to elucidate urinary metabolome changes after a regular and moderate consumption of beer and nonalcoholic beer in subjects at high cardiovascular risk

Quifer-Rada

Chiva‐Blanch

Jáuregui

et al. 2017

Molecular Nutrition Food Res

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“…While levels of total unmodified prostaglandin in urine have been correlated with only a few diseases (e.g., cardiovascular disease (Raatz et al , ) and anaphylaxis (Lieberman, )), levels of prostaglandin metabolites in urine have attracted more scrutiny. High levels of the PGD 2 metabolite tetranor PGDM in urine have been correlated with Duchenne muscular dystrophy, systemic mastocytosis, rheumatoid arthritis, colitis, and colon cancer (Nakagawa et al , ,b; Iwanaga et al , ; Cho et al , ). High levels of urinary PGE 2 metabolite levels appear to be associated with colorectal adenoma (Shrubsole et al , ; Davenport et al , ), pancreatic cancer (Zhao et al , ), and breast cancer in postmenopausal women (Cui et al , ).…”

Section: Lipid Mediators In Body Fluidsmentioning

confidence: 99%

Regulation of inflammation by lipid mediators in oral diseases

Sommakia

Baker

2016

Oral Diseases

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Lipid mediators (LM) of inflammation are a class of compounds derived from ω-3 and ω-6 fatty acids that play a wide role in modulating inflammatory responses. Some LM possess pro-inflammatory properties, while others possess pro-resolving characteristics, and the class switch from pro-inflammatory to pro-resolving is crucial for tissue homeostasis. In this article, we review the major classes of LM, focusing on their biosynthesis and signaling pathways, and their role in systemic and, especially, oral health and disease. We discuss the detection of these LM in various body fluids, focusing on diagnostic and therapeutic applications. We also present data showing gender-related differences in salivary LM levels in healthy controls, leading to a hypothesis on the etiology of inflammatory diseases, particularly, Sjögren’s Syndrome. We conclude by enumerating open areas of research where further investigation of LM is likely to result in therapeutic and diagnostic advances.

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A prostaglandin D2 metabolite is elevated in the urine of Duchenne muscular dystrophy patients and increases further from 8years old

Cited by 33 publications

References 36 publications

Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy

Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy

A discovery‐driven approach to elucidate urinary metabolome changes after a regular and moderate consumption of beer and nonalcoholic beer in subjects at high cardiovascular risk

Regulation of inflammation by lipid mediators in oral diseases

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