Ignite Creation Date:
2024-05-06 @ 7:30 PM
Last Modification Date:
2024-10-26 @ 3:08 PM
Study NCT ID:
NCT06033339
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-09-14
First Post:
2023-09-05
Brief Title:
Assessment of microRNAs Role in Familial Mediterranean Fever FMF Pathophysiology
Sponsor:
University Hospital Montpellier
Organization:
University Hospital Montpellier
Study Overview
Official Title:
Etude du rôle Des microARNs Dans la Physiopathologie de la fièvre méditerranéenne Familiale
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
miRinFMF
Brief Summary:
Familial Mediterranean Fever FMF genetic diagnosis is well established for homozygous patients On the other hand although heterozygous individuals are theoretically healthy carriers 13 of them will develop clinical symptoms of FMF and could benefit from prophylactic treatment This suggests that the disorder expression mechanisms are not fully elucidated to date The preliminary results obtained at the Institute for Regenerative Medicine and Biotherapy IRMB suggest the involvement of an epigenetic mechanism in FMF pathogenesis and our laboratory has strong arguments as to the involvement of microRNAs in particular miR-326 which are negative regulators of gene expression
This study is exploratory and aims to validate the role of miRNAs in the clinical expression of FMF in patients thus to explore the epigenetic mechanisms that may explain the variability of expression of this disorder
This study is exploratory and aims to validate the role of miRNAs in the clinical expression of FMF in patients thus to explore the epigenetic mechanisms that may explain the variability of expression of this disorder
Detailed Description:
Familial Mediterranean fever FMF is a rare autoinflammatory disorder due to mutations in the MEFV MEditerranean FeVer gene that causes recurrent episodes of fever and acute serositis peritoneum pleura synovium beginning in early childhood
MEFV gene identification allowed the development of a genomic sequencing test to confirm the diagnosis The most frequent mutations are M680I M694V V726A and M694I located in exon 10 This gene encodes the protein pyrin which following a pro-inflammatory stimulus is capable of assembling a multi-protein complex to form the pyrin inflammasome MEFV gene mutations lead to an alteration of its expression in innate immune system cells in FMF patients causing a dysregulation of the immune response which results in the abnormal secretion of certain proinflammatory cytokines such as IL-1β and IL-18
FMF is an autosomal recessive disorder Thus heterozygous individuals are theoretically healthy carriers Nevertheless in nearly 13 of patients with clinical symptoms of FMF a single heterozygous mutation is found To date there is no biological marker to distinguish heterozygous individuals who will develop the disease from those who remain healthy carriers hence diagnostic errors and delays in treatment Several hypotheses have been put forward to explain this variation in mutation expression whether it is the environment the involvement of other genes or the involvement of epigenetic modifiers
Among the mechanisms that regulate gene expression microRNAs miRNAswhich are small non-coding RNAs negatively regulate gene expression at the post-transcriptional level by binding to sequences located mainly in the region 3UTR of gene mRNA Many publications report that they are abnormally expressed in various pathologies Very recently this has been reported for FMF Several studies have focused on miRNAs as biomarkers of FMF without evaluating their role in FMF pathogenesis
Assessing the role of miRNAs specifically targeting the MEFV gene in myeloid cells especially monocytes and the functional impact of their modulation in these cells would deepen our understanding of FMF physiopathology If a miRNA specifically targeting MEFV has a proven role in FMF pathophysiology it could ultimately prove to be a prognostic biomarker of the disorder for heterozygous patients or even a future therapeutic target
MEFV gene identification allowed the development of a genomic sequencing test to confirm the diagnosis The most frequent mutations are M680I M694V V726A and M694I located in exon 10 This gene encodes the protein pyrin which following a pro-inflammatory stimulus is capable of assembling a multi-protein complex to form the pyrin inflammasome MEFV gene mutations lead to an alteration of its expression in innate immune system cells in FMF patients causing a dysregulation of the immune response which results in the abnormal secretion of certain proinflammatory cytokines such as IL-1β and IL-18
FMF is an autosomal recessive disorder Thus heterozygous individuals are theoretically healthy carriers Nevertheless in nearly 13 of patients with clinical symptoms of FMF a single heterozygous mutation is found To date there is no biological marker to distinguish heterozygous individuals who will develop the disease from those who remain healthy carriers hence diagnostic errors and delays in treatment Several hypotheses have been put forward to explain this variation in mutation expression whether it is the environment the involvement of other genes or the involvement of epigenetic modifiers
Among the mechanisms that regulate gene expression microRNAs miRNAswhich are small non-coding RNAs negatively regulate gene expression at the post-transcriptional level by binding to sequences located mainly in the region 3UTR of gene mRNA Many publications report that they are abnormally expressed in various pathologies Very recently this has been reported for FMF Several studies have focused on miRNAs as biomarkers of FMF without evaluating their role in FMF pathogenesis
Assessing the role of miRNAs specifically targeting the MEFV gene in myeloid cells especially monocytes and the functional impact of their modulation in these cells would deepen our understanding of FMF physiopathology If a miRNA specifically targeting MEFV has a proven role in FMF pathophysiology it could ultimately prove to be a prognostic biomarker of the disorder for heterozygous patients or even a future therapeutic target
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None