CRF awarded Justine Bacchetta, MD, PhD, and Irma Machuca-Gayet, PhD, their first two-year cystinosis research grant in 2018 for the study of cysteamine toxicity on the bone that became known as the CYSTEABONE project. Additional grants have been awarded every two years since then to continue the research on the pathophysiology of bone disease in nephropathic cystinosis. This is the June 2024 scientific report for the CYSTEABONE grant issued in 2022.
Summary/Abstract
Cystinosis metabolic bone disease (CMBD) corresponds to the specific bone impairment observed in patients with infantile nephropathic cystinosis; CMBD has been officially recognized in an international consensus paper in 2019 1. CMBD has a significant impact on patient’s quality of life, because of an increased frequency of bone pains, deformations and fractures occurring as early as late teenage and early adulthood. We have previously shown intrinsic specific cystinosis-related bone impairment in patients independently of mineral and bone abnormalities secondary to chronic kidney disease (CKD) 2–5.
The aims of the 2022 CYSTEABONE project were the following: 1/ to finalize the experimental part of the interleukin 1 project, so as to obtain a strong rationale to further propose a proof-of-concept trial in patients, 2/ to analyze the 1,25VD3 treated Ctns-/- Osteoblastic transcriptome to explore other regulatory pathways involved in CMBD, and 3/ to identify new targets to improve bone health in cystinosis using high-throughput pharmacological screening in a cystinosin CRISPR edited human Osteoblast-dependent osteoclastogenesis.
