Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies

• Published in: Cells (Basel, Switzerland) Switzerland), 2022-11, Vol.11 (22), p.3668
• Main Authors: Braconi, Daniela, Geminiani, Michela, Psarelli, Eftychia Eirini, Giustarini, Daniela, Marzocchi, Barbara, Rossi, Ranieri, Bernardini, Giulia, Spiga, Ottavia, Gallagher, James A, Le Quan Sang, Kim-Hanh, Arnoux, Jean-Baptiste, Imrich, Richard, Al-Sbou, Mohammed S, Gornall, Matthew, Jackson, Richard, Ranganath, Lakshminarayan R, Santucci, Annalisa
• Format: Article
• Language: English
• Subjects: Advanced Oxidation Protein Products - metabolism; Advanced Oxidation Protein Products - therapeutic use; Alkaptonuria; Alkaptonuria - complications; Alkaptonuria - drug therapy; Alkaptonuria - metabolism; Amyloid; Amyloidosis; Arthritis; Biological markers; biomarkers; Biomarkers - metabolism; Carbonyl compounds; Care and treatment; Consortia; Diagnosis; disease severity; Health aspects; Humans; inborn errors of metabolism; Inflammation; Inflammation - metabolism; Interleukin 8; Laboratories; Life sciences; Morbidity; Osteoarthritis; Oxidative Stress; Patients; Proteins; Quality of Life; Questionnaires; Risk factors; Serum Amyloid A Protein - metabolism; Software; Spectrophotometry; Statistical analysis
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11223668

Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA > 10 mg/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA > 10 mg/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis.