Purinergic Compounds in Pseudoxanthoma Elasticum

Condition(s) studied

Investigational drug(s) / intervention(s)

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

SCANNER: non-injected coronary and lower limb scanner

Study summary

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.

Eligibility

Primary outcome measure(s)

• potential role of the ADO — at inclusion
  mesure of concentration

Trial sites (2)

More Centre Hospitalier Universitaire de Nice trials in France

Other trials for the same condition