F Genovese1, A S Siebuhr2, K Musa2, J A Gallagher3, A M Milan3,4, M A Karsdal2, J Rovensky5, A C Bay-Jensen2, L R Ranganath3,4. 1. Nordic Bioscience, Herlev Hovedgade 205, 2730, Herlev, Denmark. fge@nordicbioscience.com. 2. Nordic Bioscience, Herlev Hovedgade 205, 2730, Herlev, Denmark. 3. Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L69 3GE, UK. 4. Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital Trust, Prescot Street, Liverpool, L7 8XP, UK. 5. National Institute of Rheumatic Diseases, Nabrezie, Ivana Krasku 4, 921 01, Piešťany, Slovakia.
Abstract
BACKGROUND AND AIM: Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKU patients. We tested a panel of serum and urinary biomarkers reflecting extracellular matrix remodelling (ECMR) of cartilage, bone and connective tissue in SONIA 1 patients to identify non-invasive and diagnostic biomarkers of tissue turnover in AKU. METHODS: Fasted serum and urine were retrieved from 40 SONIA 1 patients and 44 healthy controls. Established biomarkers of bone remodelling (CTX-I, P1NP, OC), cartilage remodelling (CTX-II, C2M, AGNx1) and inflammation (CRPM) as well as exploratory biomarkers of ECMR (C6M, VCANM, MIM, TIM) were measured at baseline in serum and urine by means of enzyme-linked immunosorbent assays (ELISAs) or automated systems (Elecsys 2010). RESULTS: The levels of bone resorption (CTX-I) and cartilage degradation (C2M) were elevated in AKU patients as compared to controls (p > 0.0001 and p = 0.03, respectively). Also tissue inflammation (CRPM) was elevated in AKU patients (p = 0.01). In addition all four exploratory biomarkers of ECMR (C6M, VCANM, MIM, TIM) were elevated in AKU patients compared to healthy controls. CTX-II was the only biomarker to be reduced in AKU patients. TIM was the only marker that showed a higher concentration than the normal assay range in AKU patients. CONCLUSIONS: We have identified new potential biomarkers for assessment of cartilage, bone and cardiovascular remodelling in AKU and demonstrated the robustness of the assays used to measure the biomarker concentration in biological fluids.
BACKGROUND AND AIM: Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKUpatients. We tested a panel of serum and urinary biomarkers reflecting extracellular matrix remodelling (ECMR) of cartilage, bone and connective tissue in SONIA 1 patients to identify non-invasive and diagnostic biomarkers of tissue turnover in AKU. METHODS: Fasted serum and urine were retrieved from 40 SONIA 1 patients and 44 healthy controls. Established biomarkers of bone remodelling (CTX-I, P1NP, OC), cartilage remodelling (CTX-II, C2M, AGNx1) and inflammation (CRPM) as well as exploratory biomarkers of ECMR (C6M, VCANM, MIM, TIM) were measured at baseline in serum and urine by means of enzyme-linked immunosorbent assays (ELISAs) or automated systems (Elecsys 2010). RESULTS: The levels of bone resorption (CTX-I) and cartilage degradation (C2M) were elevated in AKUpatients as compared to controls (p > 0.0001 and p = 0.03, respectively). Also tissue inflammation (CRPM) was elevated in AKUpatients (p = 0.01). In addition all four exploratory biomarkers of ECMR (C6M, VCANM, MIM, TIM) were elevated in AKUpatients compared to healthy controls. CTX-II was the only biomarker to be reduced in AKUpatients. TIM was the only marker that showed a higher concentration than the normal assay range in AKUpatients. CONCLUSIONS: We have identified new potential biomarkers for assessment of cartilage, bone and cardiovascular remodelling in AKU and demonstrated the robustness of the assays used to measure the biomarker concentration in biological fluids.
Authors: Erik B Dam; Marco Loog; Claus Christiansen; Inger Byrjalsen; Jenny Folkesson; Mads Nielsen; Arish A Qazi; Paola C Pettersen; Patrick Garnero; Morten A Karsdal Journal: Arthritis Res Ther Date: 2009-07-24 Impact factor: 5.156
Authors: Natasha Barascuk; Federica Genovese; Lise Larsen; Inger Byrjalsen; Qinlong Zheng; Shu Sun; Susanne Hosbond; Tina S Poulsen; Axel Diederichsen; Jesper M Jensen; Hans Mickley; Thomas C Register; Lars M Rasmussen; Diana J Leeming; Claus Christiansen; Morten A Karsdal Journal: Int J Clin Exp Med Date: 2013-03-21
Authors: Andrew S Davison; Brendan P Norman; Gordon A Ross; Andrew T Hughes; Milad Khedr; Anna M Milan; James A Gallagher; Lakshminarayan R Ranganath Journal: JIMD Rep Date: 2019-05-31