Purinergic Compounds in Pseudoxanthoma Elasticum (PURI-PXE)

Centre Hospitalier Universitaire de Nice

Status: Not yet enrolling

Conditions: Pseudoxanthoma Elasticum

Treatments: Biological: supplementary tubes; Radiation: SCANNER

Study type: Interventional

Funder types: Other

Identifiers

NCT07323082

25-PP-14

Details and patient eligibility

About

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder, transmitted as an autosomal recessive trait, affecting approximately 1 in 50,000 people, predominantly women. It is characterised by progressive calcification of tissues rich in elastic fibres, particularly the skin, retina and arteries. It often begins in young adults and can eventually lead to central blindness, peripheral artery disease, strokes, tendon pain, recurrent kidney stones and visible skin changes.

The diagnosis is based on clinical examination (skin papules, angioid streaks) and can be confirmed by biopsy or genotyping of the ABCC6 gene, whose mutation leads to extracellular ATP deficiency. This deficiency reduces the production of pyrophosphate (PPi), a natural inhibitor of calcification, thus promoting abnormal calcium deposits in tissues. To date, there is no curative treatment, but clinical trials are evaluating oral administration of PPi, with encouraging results.

The role of purinergic metabolism is increasingly being explored in PXE. The cascade of conversion of ATP to adenosine (ADO) via ectonucleotidase pyrophosphatase 1 (ENPP1) and 5' ectonucleotidase (NT5E) indirectly regulates the activity of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme that degrades PPi. An imbalance in this cascade could aggravate calcifications. The joint measurement of PPi, ADO and these enzymes, which has recently become possible, could not only refine our understanding of the disease, but also pave the way for new therapeutic strategies.

Enrollment: 45 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female,
• Age >18 years
• Covered by social security,
• Informed and having signed the informed consent form.

PXE patients:

- with PXE defined according to current clinical criteria for PXE (REACT-PXE and PNDS consensus) and with an ABCC6 mutation.

Exclusion criteria

• Patients treated with bisphosphonates, vitamin K antagonists, and dietary supplements containing calcium, phosphates, magnesium, zinc, or iron.
• Treatments likely to alter adenosine levels (caffeine, salbutamol, beta-blockers, etc.).
• Progressive bone diseases (osteoporosis, chondrocalcinosis, gout, etc.).
• Progressive and/or treated cancerous diseases.
• Progressive and/or treated inflammatory or autoimmune diseases.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

45 participants in 2 patient groups

PXE Patient

Experimental group

Description:

PXE Patient

Treatment:

Biological: supplementary tubes

NON PXE Patient

Other group

Description:

NON PXE Patient

Treatment:

Radiation: SCANNER

Biological: supplementary tubes