Objectives: There is a need for precision medicine and an unspoken promise of an optimal approach for identification of the right patients for value-based medicine based on big data. However, there may be a misconception that measurement of proteins is more valuable than measurement of fewer selecte...
August 26, 2021
Journal:
Clin Biochem
Author:
Karsdal MA, Rasmussen DGK, Bay-Jensen AC, Mortensen JH, Holm Nielsen S, Willumsen N, Jensen C, Manon-Jensen T, Jennings L, Reese-Petersen AL, Henriksen K, Leeming DJ, Bager CL, Genovese F, Bülow Sand JM
Abstract Objective: Dual amylin and calcitonin receptor agonists (DACRAs) are novel therapeutic agents that not only improve insulin sensitivity but also work as an adjunct to established T2DM therapies. DACRAs are currently administered once daily, though it is unknown whether DACRAs with increa...
June 29, 2021
Journal:
Molecular Metabolism
Author:
Andreassen KV, Larsen AT, Sonne N, Mohamed KE, Karsdal MA, Henriksen K
There is a need for antidiabetic agents successfully targeting insulin sensitivity and treating obesity control at the same time. The aim of this first-in-human study was (a) to evaluate safety and tolerability, (b) to evaluate pharmacokinetics and (c) to assess indications of receptor engagement of...
May 21, 2021
Journal:
Br J Clin Pharmacol
Author:
Henriksen K, Broekhuizen K, de Boon MIW, Karsdal MA, Christiansen C, Dillingh RM, de Kam M, Kumar R, Burggraaf J, Kamerling MCI, Bihlet AR
Osteogenesis imperfecta (OI), a heritable disorder caused by abnormalities in synthesis or processing of type I collagen, is characterized by skeletal fragility. Type I collagen interacts with multiple components of the extracellular matrix (ECM) including other collagens types. Thus, alterations in...
January 4, 2021
Journal:
Bone
Author:
Nicol L, Srikanth P, Henriksen K, Sun S, Smith R, Karsdal MA, Nagamani SCS, Shapiro J, Lee B, Leder BZ, Orwoll E
Osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, all have one clear common denominator; an altered turnover of bone. However, this may be more complex than a simple change in bone matrix and mineral turnover. While these diseases share a common tissue axis, thei...
December 21, 2020
Journal:
BMC Musculoskelet Disord.
Author:
Thudium CS, Nielsen SH, Sardar S, Mobasheri A, van Spil WE, Lories R, Henriksen K, Bay-Jensen AC, Karsdal MA.
Objective: Dysregulation of type I collagen metabolism has a great impact on human health. We have previously seen that matrix metalloproteinase-degraded type I collagen (C1M) is associated with early death and age-related pathologies. To dissect the biological impact of type I collagen dysregulatio...
September 20, 2020
Journal:
Neurol Genet
Author:
Tang ME, Blair JPM, Bager CL, Bay-Jensen AC, Henriksen K, Christiansen C, Karsdal MA.
Evidence indicate that the brain-specific protein, brevican, is proteolytically cleaved during neurodegeneration, hence positioning fragments of brevican as potential blood biomarkers of neurodegenerative diseases, such as dementia. We aimed to develop two assays capable of detecting the brevican N-...
Background: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene. Methods: IMO iPSCs were generated from a patient carrying a homozygous ...
May 15, 2020
Journal:
Stem Cells Res Ther
Author:
Xian X, Moraghebi R, Löfvall H, Fasth A, Henriksen K, Richter J, Woods NB, Moscatelli I
Dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for treatment of type 2 diabetes and obesity because of their beneficial effects on body weight, blood glucose, insulin sensitivity, and food preference, at least short-term. DACRAs activate the receptors for a prolonged time...
May 4, 2020
Journal:
J Pharmacol Exp Ther
Author:
Larsen AT, Sonne N, Andreassen KV, Karsdal MA, Henriksen K
Amylin treatment improves body weight and glucose control, although it is limited by a short action and need for high doses. Dual amylin and calcitonin receptor agonists (DACRAs) are dual amylin and calcitonin receptor agonists with beneficial effects beyond those of amylin. However, to what extent ...
April 21, 2020
Journal:
J Pharmacol Exp Ther
Author:
Larsen AT, Sonne N, Andreassen KV, Karsdal MA, Henriksen K
Pharmacological treatment with dual amylin and calcitonin receptor agonists (DACRAs) cause significant weight loss and improvement of glucose homeostasis. In this study, the maximally efficacious dose of the novel DACRA, KeyBiosciencePeptide (KBP)-066, was investigated. Two different rat models were...
April 14, 2020
Journal:
J Pharmacol Exp Ther
Author:
Sonne N, Larsen AT, Andreassen KV, Karsdal MA, Henriksen K
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essenti...
January 6, 2020
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Daniels SJ, Leeming DJ, Detlefsen S, Bruun MF, Hjuler ST, Henriksen K, Hein P, Krag A, Karsdal MA, Nielsen MJ, Brockbank S, Cruwys S
Blood levels of Glial Fibrillary Acidic protein (GFAP) reflect processes associated with different types of CNS injury. Evidence suggests that GFAP is cleaved by caspases during CNS injury, hence positioning GFAP fragments as potential biomarkers of injury-associated processes. We set out to develop...
November 6, 2019
Journal:
PLoS One
Author:
Jonesco DS, Hassager C, Frydland M, Kjærgaard J, Karsdal MA, Henriksen K
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th...
KBP-088 (KeyBiosciencePeptide 088) is a potent dual amylin and calcitonin receptor agonist (DACRA). DACRAs are known to elicit potent activity in terms of typical amylin-induced responses, such as reducing food intake and body weight. However, to what extent amylin infusion can mimic the effects of ...
July 1, 2019
Journal:
J Pharmacol Exp Ther
Author:
Larsen AT, Sonne N, Andreassen KV, Gehring K, Karsdal MA, Henriksen K
Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by nonfunctional osteoclasts. Approximately 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. Gene therapy represents a potential alternative treatment ...
June 10, 2019
Journal:
Hum Gene Ther
Author:
Löfvall H, Rothe M, Schambach A, Henriksen K, Richter J, Moscatelli I
OBJECTIVES: Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor ag...
June 5, 2019
Journal:
Osteoarthritis Cartilage
Author:
Katri A, Dabrowska A, Karsdal MA, Andreassen KV, Thudium CS, Henriksen K, Löfvall H
BACKGROUND: Biomarkers that predict response to anabolic therapies could expedite the development of function promoting anabolic drugs. This study aimed to identify serum biomarkers that are responsive to testosterone administration and associated with increases in fat-free mass (FFM). METHODS: Ser...
May 23, 2019
Journal:
J Clin Endocrinol Metab
Author:
Huang G, Rocha GV, Pencina KM, Cox K, Krishnan V, Henriksen K, Sissons SE, Li Z, Nedergaard AF, Karsdal MA, Sun S, Storer TW, Basaria S, Bhasin S, Mitchell PG
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a prevalent disease that is highly associated with the metabolic syndrome and type II diabetes. The development of in vivo models that reflect all nuances of the human NASH pathology is essential for drug discovery and development. We aimed to furt...
March 1, 2019
Journal:
biomed pharmacother
Author:
Daniels SJ, Leeming DJ, Detlefsen S, Bruun MF, Hjuler ST, Henriksen K, Hein P, Karsdal MA, Brockbank S, Cruwys S
C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe...
February 28, 2019
Journal:
Sci Rep
Author:
Löfvall H, Katri A, Dabrowska A, Karsdal MA, Luo Y, He Y, Manon-Jensen T, Dziegiel MH, Bay-Jensen AC, Thudium CS, Henriksen K
BACKGROUND: Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction wh...
February 22, 2019
Journal:
Arthritis Res Ther
Author:
Katri A, Dabrowska A, Löfvall H, Ding M, Karsdal MA, Andreassen KV, Henriksen K, Thudium CS
Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast p...
January 12, 2019
Journal:
Hum Genet.
Author:
Segovia-Silvestre T, Neutzsky-Wulff AV, Sorensen MG, Christiansen C, Bollerslev J, Karsdal MA, Henriksen K
N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH₂-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utili...
November 6, 2018
Journal:
Int J Mol Sci
Author:
Luo Y, He Y, Gudmann NS, Henriksen K, Simonsen O, Ladel C, Mobasheri A, Karsdal MA, Bay-Jensen AC, Michaelis M
Osteogenesis imperfecta (OI) is a rare disorder of connective tissue caused by abnormalities in the synthesis or processing of type I collagen. Type I collagen is the most abundant type of collagen and is expressed in almost all connective tissues. Given that type I collagen interacts with other col...
October 2, 2018
Journal:
Bone
Author:
Nicol L, Morar P, Wang Y, Henriksen K, Sun S, Karsdal MA, Smith R, Nagamani SCS, Shapiro J, Lee B, Orwoll E
BACKGROUND: Truncated tau appears to be specifically related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer\u0027s disease (AD); however, the relevance of truncated Tau measurement...
April 11, 2018
Journal:
PLoS One
Author:
Neergaard JS, Dragsbæk K, Christiansen C, Karsdal MA, Brix S, Henriksen K
BACKGROUND: Osteoclasts have been strongly implicated in osteoarthritic cartilage degradation, at least indirectly via bone resorption, and have been shown to degrade cartilage in vitro. The osteoclast resorption processes required to degrade subchondral bone and cartilage-the remodeling of which is...
April 10, 2018
Journal:
Arthritis Res Ther
Author:
Löfvall H, Newbould H, Karsdal MA, Dziegiel MH, Richter J, Henriksen K, Thudium CS
The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small c...
March 29, 2018
Journal:
PLoS One
Author:
Kehlet SN, Willumsen N, Armbrecht G, Dietzel R, Brix S, Henriksen K, Karsdal MA
BACKGROUND: Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer\u0027s disease have failed. OBJECTIVES: The objective of this study was to identify subgroups of individuals with object...
December 1, 2017
Journal:
J Prev Alzheimers Dis
Author:
Neergaard JS, Dragsbæk K, Christiansen C, Karsdal MA, Brix S, Henriksen K
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically...
July 20, 2017
Journal:
Hum Gene Ther
Author:
Moscatelli I, Löfvall H, Rothe M, Montano C, Kertész Z, Sirin M, Schulz AS, Schambach A, Henriksen K, Richter J, Thudium CS
There has been limited success with blood-based biomarkers of neurodegeneration. One perceived reason is that blood has no direct contact to the brain. Recently developed blood-based biomarkers of tau-degradation have shown promise as potential tools for peripheral assessment of neurodegeneration; h...
May 10, 2017
Journal:
Neurochem Int
Author:
Karsdal MA, Henriksen K, Brix S, Workman CT, Christiansen C, Dragsbæk K, Neergaard JS, Nielsen Bay H
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