Dataset Information

Galantamine attenuates autoinflammation in a mouse model of familial mediterranean fever.

ABSTRACT:

Background

Autoinflammatory diseases, a diverse group of inherited conditions characterized by excessive innate immune activation, have limited therapeutic options. Neuroimmune circuits of the inflammatory reflex control innate immune overactivation and can be stimulated to treat disease using the acetylcholinesterase inhibitor galantamine.

Methods

We tested the efficacy of galantamine in a rodent model of the prototypical autoinflammatory disease familial Mediterranean fever (FMF). Multiple chronic disease markers were evaluated in animals that received long-term galantamine treatment compared to vehicle.

Results

Long-term treatment with galantamine attenuated the associated splenomegaly and anemia which are characteristic features of this disease. Further, treatment reduced inflammatory cell infiltration into affected organs and a subcutaneous air pouch.

Conclusions

These findings suggest that galantamine attenuates chronic inflammation in this mouse model of FMF. Further research is warranted to explore the therapeutic potential of galantamine in FMF and other autoinflammatory diseases.

SUBMITTER: Mughrabi IT

PROVIDER: S-EPMC9733251 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Galantamine attenuates autoinflammation in a mouse model of familial mediterranean fever.

Mughrabi Ibrahim T IT Ochani Mahendar M Tanovic Mirza M Wang Ping P Diamond Betty B Sherry Barbara B Pavlov Valentin A VA Ozen Seza S Kastner Daniel L DL Chae Jae Jin JJ Al-Abed Yousef Y

Molecular medicine (Cambridge, Mass.) 20221209 1

<h4>Background</h4>Autoinflammatory diseases, a diverse group of inherited conditions characterized by excessive innate immune activation, have limited therapeutic options. Neuroimmune circuits of the inflammatory reflex control innate immune overactivation and can be stimulated to treat disease using the acetylcholinesterase inhibitor galantamine.<h4>Methods</h4>We tested the efficacy of galantamine in a rodent model of the prototypical autoinflammatory disease familial Mediterranean fever (FMF ...[more]

PMID: 36494621

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Project description:Inflammatory bowel disease (IBD) and familial Mediterranean fever (FMF) are inflammatory diseases with complex interactions among genetic, immune, and environmental factors. FMF is a monogenic autoinflammatory disease, characterized by recurrent febrile attacks and polyserositis, and is manifested mainly in childhood. FMF is widespread in Armenia. There are reports on the concurrent occurrence of FMF and IBD. MEFV gene mutations may have a disease-modifying effect on IBD. We have investigated the frequency of MEFV mutations and FMF in Armenian children with IBD and their influence on the clinical course. A total of 69 untreated IBD patients under 18 years of age were enrolled: 52.1% (36) had ulcerative colitis (UC), 21.7% (15) had Crohn's disease (CD), and 26.0% (18) had unclassified colitis (IBD-U). The frequency of FMF among them was 36.2% (25/69), and MEFV mutations were identified in 53.6% (37/69). The highest rate of MEFV mutations and FMF was in UC patients (61.1% and 41.6% respectively). In all, 56.7% (21/37) of IBD patients with MEFV mutations had M694V mutated alleles, mainly in compound heterozygous and heterozygous states. There were no associations in the group of IBD patients with coexisting FMF (25), either between any MEFV mutation and type of IBD or coexistence of FMF. Overall, 36.0% (9/25) of them developed VEO IBD and carried mainly the M694V mutation. We concluded that the carrier frequency of MEFV mutations among Armenian pediatric IBD patients was rather high (53.6%), especially for UC. It was suggested that the MEFV gene is not necessarily a susceptibility gene but most likely modifies the course of IBD. MEFV genetic testing was recommended for Armenian pediatric IBD patients, especially for VEO UC and IBD-U, atypical IBD course, or resistance to the conventional treatment. They should also be asked for isolated febrile attacks, recurrent arthritis, and family history, even in the absence of FMF typical symptoms, to rule out FMF and its complications.

Dataset Information

Galantamine attenuates autoinflammation in a mouse model of familial mediterranean fever.

Background

Methods

Results

Conclusions

Publications

Galantamine attenuates autoinflammation in a mouse model of familial mediterranean fever.

Similar Datasets

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