NCT04671719: GNAS-AUTAX

Determination of Circulating Autotaxin in Patients With GNAS or PTH Abnormalities

Completed Last updated 24 March 2023

What this trial tests

trial testing blood sample in Fibrous Dysplasia in 33 participants. Completed in 11 January 2023.

Timeline

10 March 2021

Primary endpoint
11 January 2023

11 January 2023

Quick facts

Lead sponsor	Hospices Civils de Lyon
Status	Completed
Study type	OBSERVATIONAL
Enrollment	33
Start date	10 March 2021
Primary completion	11 January 2023
Estimated completion	11 January 2023
Sites	3 locations across France

Drugs / interventions tested

• blood sample — full drug profile →

Conditions studied

• Fibrous Dysplasia — all drugs for Fibrous Dysplasia →
• Albright Syndrome — all drugs for Albright Syndrome →
• Adult Children — all drugs for Adult Children →
• Hypoparathyroidism — all drugs for Hypoparathyroidism →

Sponsor

Hospices Civils de Lyon — full company profile →

Who can join

10 and older, any sex, with Fibrous Dysplasia or Albright Syndrome. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

PTH secretion defects (grouped under the name hypoparathyroidism) are due to abnormalities in the PTH gene, abnormalities in the development of the parathyroid glands which synthesize PTH or abnormalities of the calcium sening receptor whose role is to adapt PTH level to ambient calcium level.

In contrast, primary hyperparathyroidism in children is also exceptional; expressed by hypercalcemia, with a renal and bon risk.

Pseudo-hypoparathyroidism, now known under the term inactivating PTH / PTHrP Signaling Disorder or iPPSD, are rare pathologies characterized by resistance to the action of PTH sometimes associated with other symptoms, in particular chondrodysplasia. They are linked to a defect in the action of a factor in the signaling pathway of G protein-coupled receptors that activate the production of cyclic AMP (cAMP). IPPSDs are most often due to a molecular defect in the GNAS gene, subject to parental imprint.

Fibrous dysplasia / McCune-Albright syndrome is a rare disease caused by somatic "gain-of-function" mutations in the GNAS gene located on chromosome 20q13 leading to activation of the protein Gαs and inappropriate production of intracellular cyclic adenosine monophosphate (cAMP). The clinical phenotype is determined by the location and extent of the tissues affected by this mutation.

Autotaxin (ATX) is a protein secreted by different tissues including the liver, fatty tissue, and bone. Today, ATX is described as the major source of LPA in the bloodstream. LPA interacts with one of its receptors on the surface of the cell membrane. Depending on the receptor engaged, one or more Gα subunits (G12 / 13, GQ, Gi / o or Gs) will activate multiple cell signaling pathways.

In bone, ATX is expressed by osteoclasts and osteoblasts. Recent laboratory data have shown that PTH stimulates ATX expression in osteoblasts in a dose-dependent manner.

The objective of this study is to provide clinical proof of concept that the PTH / Gαs / ATX pathway is truly significant in physiology and pathology, by studying the full spectrum of PTH and GNAS pathologies. If this proof of concept is obtained, therapeutic applications will probably be possible in the long term.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Trends in the Contribution of Genetic Susceptibility Loci to Hyperuricemia and Gout and Associated Novel Mechanisms.
   Zhao J, Guo S, Schrodi SJ, He D. · · 2022 · cited 11× · PMID 35813212 · DOI 10.3389/fcell.2022.937855