Ignite Creation Date:
2024-05-06 @ 6:51 PM
Last Modification Date:
2024-10-26 @ 2:55 PM
Study NCT ID:
NCT05805202
Status:
RECRUITING
Last Update Posted:
2023-04-28
First Post:
2023-03-28
Brief Title:
Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy
Sponsor:
Mario Negri Institute for Pharmacological Research
Organization:
Mario Negri Institute for Pharmacological Research
Study Overview
Official Title:
Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy
Status:
RECRUITING
Status Verified Date:
2023-04
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:
aHUS-iPSC-EC
Brief Summary:
Hemolytic Uremic Syndrome HUS is a rare disease characterized by rupture of red blood cells hemolytic anemia low platelet count thrombocytopenia and thrombotic occlusion of small vessels thrombotic microangiopathy with prevalent involvement of the kidneys
SEU in its typical form is caused by gastrointestinal infection with Escherichia coli
The atypical form of SEU aSEU which is not caused by an Escherichia coli infection is a very rare disease that may have a genetic origin it affects both children and adults and may occur in a sporadic or familial form Many studies have shown that about 60 of cases of atypical HUS are associated with genetic abnormalities of the complement system particularly the so-called alternative pathway which is a key part of the immune system for responding to infection Complement consists of a series of proteins that when activated create a so-called cascade which leads to the elimination of the infectious agent either directly or through other cells Complement is finely regulated in such a way as to prevent damage to healthy cells in ones own body Genetic defects in some of these complement regulatory proteins cause reduced protection of the endothelial surface thus the vessel wall against complement activation
Recently new mutations have been described in a gene unrelated to the complement pathway the DKGE gene which codes for the intracellular isoform of diacylglycerol kinase In these patients small renal vessel occlusion appears to occur as a result of altered endothelial cell proliferation and angiogenesis through mechanisms apparently unrelated to complement activation However to date these mechanisms are poorly studied Throughout the entire project statistical methods will be applied to optimize the characterization of the abnormalities in phenotype and function of iPSC-EC derived from aHUS patients with either DGKE or MCP genetic abnormalities as compared with control iPSC-EC including identifying potential drugs that could correct the abnormalities
SEU in its typical form is caused by gastrointestinal infection with Escherichia coli
The atypical form of SEU aSEU which is not caused by an Escherichia coli infection is a very rare disease that may have a genetic origin it affects both children and adults and may occur in a sporadic or familial form Many studies have shown that about 60 of cases of atypical HUS are associated with genetic abnormalities of the complement system particularly the so-called alternative pathway which is a key part of the immune system for responding to infection Complement consists of a series of proteins that when activated create a so-called cascade which leads to the elimination of the infectious agent either directly or through other cells Complement is finely regulated in such a way as to prevent damage to healthy cells in ones own body Genetic defects in some of these complement regulatory proteins cause reduced protection of the endothelial surface thus the vessel wall against complement activation
Recently new mutations have been described in a gene unrelated to the complement pathway the DKGE gene which codes for the intracellular isoform of diacylglycerol kinase In these patients small renal vessel occlusion appears to occur as a result of altered endothelial cell proliferation and angiogenesis through mechanisms apparently unrelated to complement activation However to date these mechanisms are poorly studied Throughout the entire project statistical methods will be applied to optimize the characterization of the abnormalities in phenotype and function of iPSC-EC derived from aHUS patients with either DGKE or MCP genetic abnormalities as compared with control iPSC-EC including identifying potential drugs that could correct the abnormalities
Detailed Description:
None
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