The Situation of Chemokine Ligands and Receptors Gene Expression, Following the Oral Administration of Drug Mannuronic Acid in Rheumatoid Arthritis Patients.
Administration, Oral
Adolescent
Adult
Aged
Anti-Inflammatory Agents, Non-Steroidal
/ administration & dosage
Arthritis, Rheumatoid
/ drug therapy
Chemokines
/ metabolism
Female
Gene Expression Regulation
/ drug effects
Hexuronic Acids
/ administration & dosage
Humans
Leukocytes, Mononuclear
/ drug effects
Male
Middle Aged
Patents as Topic
Receptors, Chemokine
/ genetics
Young Adult
Chemokine
Clinical trial
DMARDs
M2000
Mannuronic acid
NSAIDs.
Journal
Recent patents on inflammation & allergy drug discovery
ISSN: 1872-213X
Titre abrégé: Recent Pat Inflamm Allergy Drug Discov
Pays: United Arab Emirates
ID NLM: 101309297
Informations de publication
Date de publication:
2020
2020
Historique:
received:
08
05
2019
revised:
02
11
2019
accepted:
02
11
2019
pubmed:
16
11
2019
medline:
15
12
2020
entrez:
16
11
2019
Statut:
ppublish
Résumé
Regarding the leukocytes infiltration into the synovium of Rheumatoid Arthritis (RA) patients is mostly mediated by chemokine ligands and receptors, and following the efficient and motivating results of international Phase III clinical trial of β-D-Mannuronic acid (M2000) patented EP067919 (2017), as a novel anti-inflammatory drug, in patients with RA, the present research was designed. This study aimed to assess the oral administration effects of this new drug on gene expression of some chemokine receptors and ligands, including CXCR4, CXCR3, CCR2, CCR5 and CCL2/MCP-1 in PBMCs of patients with active form of RA. Twelve patients suffering from RA, with inadequate response to conventional drugs were selected (Clinical trial identifier IRCT2017100213739N10) and 1000mg/day of M2000 was orally administrated to them for 12 weeks. The mRNA expression of target molecules was then evaluated in PBMCs of the patients before and after treatment with M2000 using real-time PCR and was compared to healthy controls. Patents related to this study were also reviewed. The results showed that M2000 was able to significantly down-regulate the mRNA expression of CXCR4, CCR2 and CCL2/MCP-1 in the PBMCs of the RA patients. It should be noted that the gene expression situation of the target molecules was in coordinate with the clinical and paraclinical assessments in the patients. Taken together, the results of this investigation revealed the part of molecular and immunological mechanisms of drug Mannuronic acid (M2000) in the treatment of RA, based on chemokine ligands and receptors mediated processes.
Sections du résumé
BACKGROUND
BACKGROUND
Regarding the leukocytes infiltration into the synovium of Rheumatoid Arthritis (RA) patients is mostly mediated by chemokine ligands and receptors, and following the efficient and motivating results of international Phase III clinical trial of β-D-Mannuronic acid (M2000) patented EP067919 (2017), as a novel anti-inflammatory drug, in patients with RA, the present research was designed.
OBJECTIVES
OBJECTIVE
This study aimed to assess the oral administration effects of this new drug on gene expression of some chemokine receptors and ligands, including CXCR4, CXCR3, CCR2, CCR5 and CCL2/MCP-1 in PBMCs of patients with active form of RA.
METHODS
METHODS
Twelve patients suffering from RA, with inadequate response to conventional drugs were selected (Clinical trial identifier IRCT2017100213739N10) and 1000mg/day of M2000 was orally administrated to them for 12 weeks. The mRNA expression of target molecules was then evaluated in PBMCs of the patients before and after treatment with M2000 using real-time PCR and was compared to healthy controls. Patents related to this study were also reviewed.
RESULTS
RESULTS
The results showed that M2000 was able to significantly down-regulate the mRNA expression of CXCR4, CCR2 and CCL2/MCP-1 in the PBMCs of the RA patients. It should be noted that the gene expression situation of the target molecules was in coordinate with the clinical and paraclinical assessments in the patients.
CONCLUSION
CONCLUSIONS
Taken together, the results of this investigation revealed the part of molecular and immunological mechanisms of drug Mannuronic acid (M2000) in the treatment of RA, based on chemokine ligands and receptors mediated processes.
Identifiants
pubmed: 31729947
pii: IAD-EPUB-102354
doi: 10.2174/1872213X13666191114111822
pmc: PMC7509734
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Chemokines
0
Hexuronic Acids
0
Receptors, Chemokine
0
mannuronic acid
980IT47Y34
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
69-77Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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