Purinergic Compounds in Pseudoxanthoma Elasticum

Официальное название

Role of Purinergic Compounds in the Vascular Pathology of Pseudoxanthoma Elasticum

Обзор

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.

Вмешательства

• Биопрепарат supplementary tubes
  * One 2.5 ml EDTA blood tube for PPi measurement. * Special blotting paper for collecting blood drops for ADO measurement. * 7.5 ml whole blood for ectoenzyme measurement
• Лучевая терапия SCANNER
  non-injected coronary and lower limb scanner

Первичные конечные точки

• potential role of the ADO [Срок оценки: at inclusion]

Вторичные конечные точки (2)

• correlation between ADO, PPi and ectoenzymatic activities [Срок оценки: at inclusion]
• correlation between ADO, PPi and calcification score [Срок оценки: at inclusion]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Франция · 2 центра

• Angers University hospital — Angers
• Nice University hospital — Nice

Идентификаторы

NCT: NCT07323082 · 25-PP-14

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗