MedTrace Logo

Protection Response to Cellular Stress in BPAN's Patient Study

NCT05954494 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 21

Last updated 2025-12-19

No results posted yet for this study

Summary

BPAN (beta-propeller associated neurodegeneration) is caused by mutations in the autophagy gene WDR45, also known as WIPI4, located on the X chromosome. Mutations in WDR45 result in neurodevelopmental impairment in girls and early-onset epileptic encephalopathy in boys, followed by neurodegeneration in adults (SENDA). This condition is a subtype of neurodegeneration with brain iron overload (NBIA). BPAN is the most recently identified subtype of NBIA and it is important to understand how mutations in WDR45, present in patients∙e∙s, cause cell death.

Autophagy is a cell survival mechanism responsible for the degradation and recycling of cell contents. It has been proposed that autophagy becomes less efficient during normal aging, which could cause neuronal death and thus lead to neurodegeneration.

Reduced autophagic activity has been observed in lymphoblastic cells of BPAN patients and in brains of KO mice for WDR45. The current hypothesis to explain the pathology associated with WDR45 mutations is that a defect in autophagy leads to neurodegeneration. However, we do not know if the autophagy defect is causal or if other deregulations of cellular responses contribute to neurodegeneration. Preliminary results from Pr. Bertrand Mollereau's team suggest that a global deregulation of cellular stress responses may be induced in patient cells. This includes in particular the endoplasmic reticulum response to stress (UPR response) as well as lipid storage mechanisms.

The investigators hypothesize that cells from patients carrying pathogenic variants of WDR45 will exhibit deregulation of cellular stress response pathways.

Conditions

  • Children and Adults With BPAN Carrying Pathogenic Variants of WDR45

Interventions

BIOLOGICAL

BPAN Patients

Patients, children or adults with a neurological impairment (epilepsy, dystonia, cognitive impairment...) related to a pathogenic variant of the WDR45 gene

Sponsors & Collaborators

  • Hospices Civils de Lyon

    lead OTHER

Eligibility

Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-10-23
Primary Completion
2025-10-23
Completion
2025-10-23

Countries

  • France

Study Locations

More Related Trials

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 NCT05954494 on ClinicalTrials.gov