An observational study in Children and Adults With BPAN Carrying Pathogenic Variants of WDR45, sponsored by Hospices Civils de Lyon. Completed at 2 sites in France. Per ClinicalTrials.gov, last updated 2025-12-19.
Sponsored by Hospices Civils de Lyon · Observational
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.
Hospices Civils de Lyon is the lead sponsor of 1,826 studies on the registry; 439 are open to participants now.
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Community sample of patients, organized with patient's associations and major reference centers. As this is a rare genetic disorder with no treatment, we conduct this research at the request of the above-mentioned patient associations.
At present, about twenty patients are followed for this pathology in France and 2 to 3 patients are diagnosed on average each year. Assuming a refusal rate of 5% (knowing that this study is based on the wishes of the patients' families), we plan to include a total of 20 patients.
Exclusion Criteria:
- According to the order of 12/04/2018 of the Public Health Code : Weight ≤ 12.5 kg for a 10mL sample or For 2 male and 2 female Lyon patients : Weight ≤ 25 kg for a 20mL sample
Patients, children or adults with a neurological impairment (epilepsy, dystonia, cognitive impairment...) related to a pathogenic variant of the WDR45 gene
Autophagic capacity of BPAN cells as marker of cellular stress response
* Expression of LC3 protein * Expression of p62 protein
Time frame: At study completion in an average of 12 months
Plan to share: No
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This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
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Hospices Civils de Lyon