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https://www.readbyqxmd.com/read/29792929/recent-advances-in-intra-articular-drug-delivery-systems-for-osteoarthritis-therapy
#1
REVIEW
Pierre Maudens, Olivier Jordan, Eric Allémann
Osteoarthritis (OA) is the most common degenerative disease of the joint. Despite many reports and numerous clinical trials, OA is not entirely understood, and there is no effective treatment available for this disease. To satisfy this unmet medical need, drug delivery systems (DDSs) containing disease-modifying OA drugs (DMOADs) for intra-articular (IA) administration are required to improve the health of OA patients. DDSs should provide controlled and/or sustained drug release, enabling long-term treatment with a reduced number of injections...
May 21, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29787833/dehydroepiandrosterone-molecular-mechanisms-and-therapeutic-implications-in-osteoarthritis
#2
REVIEW
Kai Huang, Li-Dong Wu
Dehydroepiandrosterone (DHEA), a 19-carbon steroid hormone primarily synthesized in the adrenal gland, exerts a chondroprotective effect against osteoarthritis (OA) and has been considered an effective candidate of disease-modifying OA drugs (DMOADs) that slow disease progression. We and others previously demonstrated that DHEA exerted a beneficial effect on osteoarthritic cartilage by positively modulating the balance between anabolic and catabolic factors (e.g., MMPs/TIMP-1, ADAMTS/TIMP-3 and cysteine proteinases/cystatin C), inhibiting catabolic signaling pathways (e...
May 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29775732/il4-10-fusion-protein-has-chondroprotective-anti-inflammatory-and-potentially-analgesic-effects-in-the-treatment-of-osteoarthritis
#3
C Steen-Louws, J Popov-Celeketic, S C Mastbergen, K Coeleveld, C E Hack, N Eijkelkamp, M Tryfonidou, S Spruijt, J A G van Roon, F P J G Lafeber
OBJECTIVE: Effective disease-modifying drugs for osteoarthritis (DMOAD) should preferably have chondroprotective, anti-inflammatory, and analgesic activity combined in a single molecule. We developed a fusion protein of IL4 and IL10 (IL4-10 FP), in which the biological activity of both cytokines is preserved. The present study evaluates the chondroprotective, anti-inflammatory, and analgesic activity of IL4-10 FP in in vitro and in vivo models of osteoarthritis. METHODS: Human osteoarthritic cartilage tissue and synovial tissue were cultured with IL4-10 FP...
May 15, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29752462/the-role-of-radiography-and-mri-for-eligibility-assessment-in-dmoad-trials-of-knee-oa
#4
REVIEW
Frank W Roemer, C Kent Kwoh, Daichi Hayashi, David T Felson, Ali Guermazi
Currently, no disease-modifying osteoarthritis drugs (DMOADs) have been approved. Past clinical trials have failed for several reasons, including the commonly applied definition of eligibility based on radiographic assessment of joint structure. In the context of precision medicine, finding the appropriate patient for a specific treatment approach will be of increasing relevance. Phenotypic stratification by use of imaging at the time of determining eligibility for clinical trials will be paramount and cannot be achieved using radiography alone...
May 11, 2018: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/29233174/sprifermin-rhfgf18-modulates-extracellular-matrix-turnover-in-cartilage-explants-ex-vivo
#5
Ditte Reker, Cecilie F Kjelgaard-Petersen, Anne Sofie Siebuhr, Martin Michaelis, Anne Gigout, Morten A Karsdal, Christoph Ladel, Anne C Bay-Jensen
BACKGROUND: Sprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix (ECM) production. To gain further insight into the process of sprifermin in the cartilage tissue, this study aimed at investigating the ECM turnover of articular cartilage explants in a longitudinal manner...
December 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29205258/sustained-intra-cartilage-delivery-of-low-dose-dexamethasone-using-a-cationic-carrier-for-treatment-of-post-traumatic-osteoarthritis
#6
A G Bajpayee, R E De la Vega, M Scheu, N H Varady, I A Yannatos, L A Brown, Y Krishnan, T J Fitzsimons, P Bhattacharya, E H Frank, A J Grodzinsky, R M Porter
Disease-modifying osteoarthritis drugs (DMOADs) should reach their intra-tissue target sites at optimal doses for clinical efficacy. The dense, negatively charged matrix of cartilage poses a major hindrance to the transport of potential therapeutics. In this work, electrostatic interactions were utilised to overcome this challenge and enable higher uptake, full-thickness penetration and enhanced retention of dexamethasone (Dex) inside rabbit cartilage. This was accomplished by using the positively charged glycoprotein avidin as nanocarrier, conjugated to Dex by releasable linkers...
December 5, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/29098574/immune-contributions-to-osteoarthritis
#7
REVIEW
Erika Barboza Prado Lopes, Adrian Filiberti, Syed Ali Husain, Mary Beth Humphrey
PURPOSE OF THE REVIEW: Mounting evidence supports a role of low-grade inflammation in the pathophysiology of osteoarthritis (OA). We review and discuss the role of synovitis, complement activation, cytokines, and immune cell population in OA. RECENT FINDINGS: Using newer imaging modalities, synovitis is found in the majority of knees with OA. Complement activation and pro-inflammatory cytokines play a significant role in the development of cartilage destruction and synovitis...
December 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/29079516/pharmacological-blockade-of-the-wnt-beta-catenin-signaling-a-possible-first-in-kind-dmoad
#8
EDITORIAL
F Dell'Accio, F Cailotto
No abstract text is available yet for this article.
January 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29040157/development-and-use-of-biochemical-markers-in-osteoarthritis-current-update
#9
Anne C Bay-Jensen, Christian S Thudium, Ali Mobasheri
PURPOSE OF REVIEW: There is an increasing demand for noninvasive and descriptive biochemical markers (biomarkers) in osteoarthritis; for enabling early drug development (including translational research), evaluating clinical trial at an early stage and for subtyping. Purpose of the review is to review and comment on current availability of such biomarkers. RECENT FINDINGS: Many different biomarkers have been tested in the last 18 months. The main focus has been on testing whether the biomarkers, whether is reflect joint tissue turnover or inflammatory status, can differentiate osteoarthritis patients from healthy controls or whether the biomarkers are associated with progression...
January 2018: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29038075/biochemical-marker-discovery-testing-and-evaluation-for-facilitating-oa-drug-discovery-and-development
#10
REVIEW
Anne-Christine Bay-Jensen, Christian S Thudium, Oreste Gualillo, Ali Mobasheri
Osteoarthritis (OA) is the most common form of joint disease. This presents the OA research community and pharmaceutical companies developing disease-modifying OA drugs (DMOADs) with great opportunities. The different OA subtypes complicate the traditional approaches for developing new treatments. If we can identify new markers that can distinguish different subtypes this could greatly facilitate drug development from early discovery to late clinical development. Nevertheless, the current approaches result in poorly targeted treatments and the inability to recruit the right patients for clinical trials...
February 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/28978991/osteoarthritis-wnt-inhibitor-shows-potential-as-a-dmoad
#11
Sarah Onuora
No abstract text is available yet for this article.
November 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28955780/pharmacological-treatment-with-diacerein-combined-with-mechanical-stimulation-affects-the-expression-of-growth-factors-in-human-chondrocytes
#12
Bibiane Steinecker-Frohnwieser, Heike Kaltenegger, Lukas Weigl, Anda Mann, Werner Kullich, Andreas Leithner, Birgit Lohberger
BACKGROUND: Osteoarthritis (OA) as the main chronic joint disease arises from a disturbed balance between anabolic and catabolic processes leading to destructions of articular cartilage of the joints. While mechanical stress can be disastrous for the metabolism of chondrocytes, mechanical stimulation at the physiological level is known to improve cell function. The disease modifying OA drug (DMOAD) diacerein functions as a slowly-acting drug in OA by exhibiting anti-inflammatory, anti-catabolic, and pro-anabolic properties on cartilage...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28711582/a-novel-wnt-pathway-inhibitor-sm04690-for-the-treatment-of-moderate-to-severe-osteoarthritis-of-the-knee-results-of-a-24-week-randomized-controlled-phase-1-study
#13
Y Yazici, T E McAlindon, R Fleischmann, A Gibofsky, N E Lane, A J Kivitz, N Skrepnik, E Armas, C J Swearingen, A DiFrancesco, J R S Tambiah, J Hood, M C Hochberg
OBJECTIVE: To assess the safety, pharmacokinetics, and exploratory efficacy of SM04690, a novel Wnt pathway inhibitor, as a potential disease modifying treatment for knee osteoarthritis (OA). DESIGN: Subjects with Kellgren-Lawrence grade 2-3 knee OA were randomized in successive dose-escalation cohorts to receive a knee intra-articular (IA) injection with 0.03, 0.07, or 0.23 mg SM04690, or placebo (PBO) (4:1 ratio). Safety, pharmacokinetics, efficacy (WOMAC Total/Function/Pain, Pain VAS, Physician Global Assessment [MDGA], and OMERACT-OARSI Response), OA-related biomarker (P1NP, ß-CTX, and cartilage oligomeric matrix protein [COMP]), and radiographic/imaging data were collected at baseline and during 24-week follow-up...
October 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28645453/choice-of-knee-cartilage-thickness-change-metric-for-different-treatment-goals-in-efficacy-studies
#14
Robert J Buck, Marie-Pierre Hellio Le Graverand, Wolfgang Wirth, Felix Eckstein
INTRODUCTION: In knee osteoarthritis, local increase and decrease in cartilage thickness has been observed over short time intervals. Hence, averaging cartilage change across large regions may not capture the complexity of structural alterations in disease progression. This study aims to examine the relative performance of different metrics of cartilage thickness change for different clinical studies scenarios. MATERIALS AND METHODS: Metrics for assessing cartilage thickness change were characterized by conventional measures of change versus absolute values (the magnitude) of change, and by different methods of summarizing change over (sub-) regions...
May 30, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28092725/strontium-ranelate-a-promising-disease-modifying-osteoarthritis-drug
#15
REVIEW
Weiyu Han, Shicai Fan, Xiaochun Bai, Changhai Ding
The articular cartilage and subchondral bone may have potential crosstalk in the development and progression of osteoarthritis (OA). Strontium ranelate (SrR) has the ability to dissociate the bone remodeling process and to change the balance between bone resorption and bone formation. Its effect on subchondral bone makes it a potential disease- modifying osteoarthritis drug (DMOAD) in the treatment of OA. The aim of the current review is to summarize up-to-date pharmacological and clinical data of SrR for OA treatment...
March 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27562879/monoclonal-antibodies-for-the-treatment-of-osteoarthritis
#16
REVIEW
Shuang Zheng, David J Hunter, Jianhua Xu, Changhai Ding
Osteoarthritis (OA) is a multifactorial chronic joint disease, and so far, there are no approved disease-modifying anti-OA drugs (DMOADs). There is an urgent need to develop therapies for different phenotypes of OA. Monoclonal antibodies (mAb) may slow structural progression, control inflammation and relieve pain, and thus have the potential to be DMOADs. Areas covered: In this review, the authors searched the literature on PubMed, EMBASE and the Cochrane Library using keywords, including mAbs, biological agents, OA and osteoarthritis, electronically up to May 2016...
December 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27546496/an-update-on-the-pathophysiology-of-osteoarthritis
#17
REVIEW
Ali Mobasheri, Mark Batt
INTRODUCTION: Osteoarthritis (OA) is one of the most common forms of arthritis. There is accumulating evidence to suggest that OA is an inflammatory disease of the entire synovial joint and has multiple phenotypes. This presents the OA research community with new challenges and opportunities. The main challenge is to understand the root cause of the disease and identify differences and similarities between OA phenotypes. The key opportunity is the possibility of developing personalized and individualized prevention and treatment strategies for OA patients with different phenotypes of the disease...
December 2016: Annals of Physical and Rehabilitation Medicine
https://www.readbyqxmd.com/read/27492463/disease-modifying-treatments-for-osteoarthritis-dmoads-of-the-knee-and-hip-lessons-learned-from-failures-and-opportunities-for-the-future
#18
REVIEW
M A Karsdal, M Michaelis, C Ladel, A S Siebuhr, A R Bihlet, J R Andersen, H Guehring, C Christiansen, A C Bay-Jensen, V B Kraus
Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying treatments for OA. Insights gleaned from these attempts suggest that these failures arose from unrealistic hypotheses, sub-optimal selection of patient populations or drug dose, and/or inadequate sensitivity of the trial endpoints...
December 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27463798/current-opinion-where-are-we-in-our-understanding-and-treatment-of-osteoarthritis
#19
REVIEW
Anthony Robin Poole
There has been important recent progress in our understanding of the molecular pathology of osteoarthritis (OA) and how it might be treated. New technologies have been developed and others refined to identify patients for recruitment in clinical trials who exhibit measurable progression. Combined with the ability to determine more effectively short-term efficacy of treatment, significant obstacles are being removed that have negated or led to the failure of earlier trials. The future for disease-modifying osteoarthritis drug (DMOAD) development and more effective pain control is therefore much more encouraging...
2016: Swiss Medical Weekly
https://www.readbyqxmd.com/read/26980567/chondroitin-sulfate-and-glucosamine-as-disease-modifying-anti-osteoarthritis-dru-gs-dmoads
#20
REVIEW
Veronica Mantovani, Francesca Maccari, Nicola Volpi
Osteoarthritis is a disabling affliction expected to increase in the coming decades, and disease- modifying osteoarthritis drugs (DMOADs) would be highly desirable adjuncts to symptomatic relief and structure reconstruction as they may delay the disease process. Chondroitin sulfate and glucosamine have been observed to exert beneficial effects on the metabolism of various cells involved in osteoarthritis as well as in animal models and clinical trials. Clinical trials have reported beneficial effects of both these biological agents, alone or in combination, on pain and functions as well as their structure-modifying capacity reported and analyzed in recent meta-analyses...
2016: Current Medicinal Chemistry
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