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Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy

NCT05805202 · Status: RECRUITING · Phase: NA · Type: INTERVENTIONAL · Enrollment: 112

Last updated 2025-09-29

No results posted yet for this study

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 one's 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

Conditions

  • Atypical Hemolytic Uremic Syndrome

Interventions

OTHER

Blood sampling and urine analysis

A blood sample of 10- 20 ml from pediatric patients, 30-50 ml from adult patients will be collected for each patient and healthy voluntarees

Sponsors & Collaborators

  • Mario Negri Institute for Pharmacological Research

    lead OTHER

Study Design

Allocation
NON_RANDOMIZED
Purpose
SCREENING
Masking
NONE
Model
PARALLEL

Eligibility

Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2023-05-03
Primary Completion
2026-12-31
Completion
2026-12-31

Countries

  • Italy

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05805202 on ClinicalTrials.gov