Cystinosis and Mitochondrial Metabolism (CYSTI-MITO)

Civil Hospices of Lyon

Status: Not yet enrolling

Conditions: Cystinosis; Native Kidney

Treatments: Other: Mitochondrial metabolism

Study type: Interventional

Funder types: Other

Identifiers

NCT07319091

69HCL25_0542

Details and patient eligibility

About

Cystinosis is a monogenic autosomal recessive lysosomal storage disease with complete penetrance, caused by a biallelic mutation in the CTNS gene (17p13.2) encoding cystinosin, a ubiquitous membrane protein whose role is to clear cystine into the cytosol. Its dysfunction in patients with cystinosis leads to systemic accumulation of cystine, an oxidised dimer of cysteines linked by a disulphide bridge, in the lysosomal space, and irreversible cellular dysfunction. Renal damage is at the forefront, with Fanconi syndrome (proximal tubulopathy) and chronic renal failure developing early in childhood/adolescence. There are also multi-systemic disorders, notably endocrine and ophthalmological. Cysteamine is an amino thiol which reduces the level of intra-lysosomal cystine by breaking the disulphide strands of cystine, giving two cysteines which complex with cysteamine to leave the lysosome. Since the late 1980s, there has been an immediate-release form of the drug, which has considerably improved overall patient survival despite having a major impact on quality of life. This improvement in survival has also led to the emergence of later complications that were not previously observed. This musculoskeletal complication (described in an international consensus in 2019), known as 'CMBD' for Cystinosis Metabolic Bone Disease, may be explained at least in part by an intrinsic defect in the osteoblast and osteoclast that contribute to the human bone phenotype. This intrinsic bone defect appears to be responsible for premature ageing. In order to identify potential future therapeutic targets for CMBD, it is essential to gain a better understanding of the underlying pathophysiological mechanisms.

To better understand premature aging in extra-renal damage in cystinosis, it seems relevant to investigate energy metabolism dysfunction, particularly mitochondrial dysfunction.

Enrollment: 25 estimated patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patient with genetically confirmed nephropathic cystinosis
• Men and women, children and adults with cystinosis
• Undergoing conservative treatment on native kidneys
• Age ≥ 2 years
• Patients receiving oral cysteamine
• Patients with social security coverage
• Informed consent signed by the participant or parents or legal guardians before participating in the study

Exclusion criteria

• Patient not complying with study procedures
• Transplant or dialysis patient
• Patient on anticalcineurin
• Pregnant or breast-feeding woman
• Person deprived of liberty by a judicial or administrative decision
• Person not affiliated to a social security scheme or beneficiaries of a similar scheme

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Cystinosis patient

Other group

Description:

Patient with genetically confirmed nephropathic cystinosis Men and women, children and adults with cystinosis Undergoing conservative treatment on native kidneys Age ≥ 2 years Patients receiving oral cysteamine Patients with social security coverage Informed consent signed by the participant or parents or legal guardians before participating in the study

Treatment:

Other: Mitochondrial metabolism