Nordic Bioscience A/S, 2730 Herlev, Denmark.
Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool L69 3BX, UK.
Int J Mol Sci. 2023 Jul 1;24(13):10996. doi: 10.3390/ijms241310996.
Nitisinone has been approved for treatment of alkaptonuria (AKU). Non-invasive biomarkers of joint tissue remodelling could aid in understanding the molecular changes in AKU pathogenesis and how these can be affected by treatment. Serological and urinary biomarkers of type I collagen and II collagen in AKU were investigated in patients enrolled in the randomized SONIA 2 (NCT01916382) clinical study at baseline and yearly until the end of the study (Year 4). The trajectories of the biomarkers over time were observed. After treatment with nitisinone, the biomarkers of type I collagen remodelling increased at Year 1 (19% and 40% increase in CTX-I and PRO-C1, respectively), which was potentially reflected in the higher degree of mobility seen following treatment. The biomarkers of type II collagen remodelling decreased over time in the nitisinone group: C2M showed a 9.7% decline at Year 1, and levels then remained stable over the following visits; CTX-II showed a 26% decline at Year 3 and 4 in the nitisinone-treated patients. Nitisinone treatment induced changes in biomarkers of bone and cartilage remodelling. These biomarkers can aid patient management and deepen our knowledge of the molecular mechanisms of this rare disease.
尼替西农已被批准用于治疗尿黑酸尿症（AKU）。关节组织重塑的非侵入性生物标志物可帮助了解 AKU 发病机制中的分子变化，以及这些变化如何受到治疗的影响。在 SONIA 2 （NCT01916382）随机临床试验中招募的患者在基线和每年研究结束时（第 4 年）检查了 AKU 中 I 型和 II 型胶原的血清学和尿生物标志物。观察了生物标志物随时间的变化轨迹。尼替西农治疗后，I 型胶原重塑的生物标志物在第 1 年增加（CTX-I 和 PRO-C1 分别增加 19%和 40%），这可能反映了治疗后更高的活动度。尼替西农组的 II 型胶原重塑生物标志物随时间逐渐下降：C2M 在第 1 年下降 9.7%，随后在接下来的访视中保持稳定；CTX-II 在尼替西农治疗的患者中在第 3 年和第 4 年下降了 26%。尼替西农治疗诱导了骨和软骨重塑的生物标志物变化。这些生物标志物可以辅助患者管理，并加深我们对这种罕见疾病的分子机制的认识。
