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Disease modifying drugs

Claire Daien, Charlotte Hua, Cécile Gaujoux-Viala, Alain Cantagrel, Madeleine Dubremetz, Maxime Dougados, Bruno Fautrel, Xavier Mariette, Nathalie Nayral, Christophe Richez, Alain Saraux, Gérard Thibaud, Daniel Wendling, Laure Gossec, Bernard Combe
The 2014 French Society for Rheumatology (Société Française de Rheumatologie, SFR) recommendations about the management of rheumatoid arthritis (RA) have been updated by a task force composed of 12 expert rheumatologists, 2 patient self-help group representatives, and an occupational therapist. The material used by the task force included recent EULAR recommendations, a systematic literature review, and expert opinion. Four general principles and 15 recommendations were developed. The general principles emphasize the need for shared decision-making between the rheumatologist and the patient and for a global management program including both pharmacological and nonpharmacological treatments...
October 10, 2018: Joint, Bone, Spine: Revue du Rhumatisme
Stefanie Kuerten, Leila J Jackson, Joel Kaye, Timothy L Vollmer
Growing evidence indicates that B cells play a key role in the pathogenesis of multiple sclerosis (MS). B cells occupy distinct central nervous system (CNS) compartments in MS, including the cerebrospinal fluid and white matter lesions. Also, it is now known that, in addition to entering the CNS, B cells can circulate into the periphery via a functional lymphatic system. Data suggest that the role of B cells in MS mainly involves their in situ activation in demyelinating lesions, leading to altered pro- and anti-inflammatory cytokine secretion, and a highly effective antigen-presenting cell function, resulting in activation of memory or naïve T cells...
October 12, 2018: CNS Drugs
Niko M Perttila, Hanna Öhman, Timo E Strandberg, Hannu Kautiainen, Minna Raivio, Marja-Liisa Laakkonen, Niina Savikko, Reijo S Tilvis, Kaisu H Pitkälä
INTRODUCTION: No study has investigated how exercise modifies the effect of fall-related drugs (FRDs) on falls among people with Alzheimer's disease (AD). OBJECTIVE: The aim of this study was to investigate how exercise intervention and FRDs interact with fall risk among patients with AD. METHODS: In the FINALEX trial, community-dwelling persons with AD received either home-based or group-based exercise twice weekly for 1 year (n =129); the control group received normal care (n =65)...
October 13, 2018: Drugs & Aging
Man Ki Kwok, Shi Lin Lin, C Mary Schooling
BACKGROUND: Alzheimer's disease (AD) is a devastating condition with no known effective drug treatments. Existing drugs only alleviate symptoms. Given repeated expensive drug failures, we assessed systematically whether approved and investigational AD drugs are targeting products of genes strongly associated with AD and whether these genes are targeted by existing drugs for other indications which could be re-purposed. METHODS: We identified genes strongly associated with late-onset AD from the loci of genetic variants associated with AD at genome-wide-significance and from a gene-based test applied to the most extensively genotyped late-onset AD case (n = 17,008)-control (n = 37,154) study, the International Genomics of Alzheimer's Project...
October 9, 2018: EBioMedicine
Cara M Altimus, Kirstie Keller, Patrick Brannelly, Erin Ross, Chang-Ting Lin, Ekemini A U Riley, LaTese Briggs, Jeremy Smith, Melissa Stevens
Neurodegenerative diseases encompass a range of diagnoses, such as Alzheimer's disease and Parkinson's disease. Despite decades of advancements in understanding the neurobiology of individual diseases, this class has few disease-modifying therapeutics and a paucity of biomarkers for diagnosis or progression. However, tau protein aggregation has emerged as a potential unifying factor across several neurodegenerative diseases, which has prompted a rapid growth in tau-related funding. In spite of this growth, research funding in this area is not in line with the immense magnitude of disease burden, and drug discovery and clinical research remain underfunded...
October 3, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Ludovico Abenavoli, Tetyana Falalyeyeva, Luigi Boccuto, Olena Tsyryuk, Nazarii Kobyliak
The main treatments for patients with nonalcoholic fatty liver disease (NAFLD) are currently based on lifestyle changes, including ponderal decrease and dietary management. However, a subgroup of patients with nonalcoholic steatohepatitis (NASH), who are unable to modify their lifestyle successfully, may benefit from pharmaceutical support. Several drugs targeting pathogenic mechanisms of NAFLD have been evaluated in clinical trials for the treatment of NASH. Farnesoid X receptor (FXR) is a nuclear key regulator controlling several processes of the hepatic metabolism...
October 11, 2018: Pharmaceuticals
Vicente E Torres
No treatment until now has directly targeted the mechanisms responsible for the development and growth of cysts in autosomal dominant polycystic kidney disease (ADPKD). Strong rationale and preclinical studies using in vitro and in vivo models justified the launching of two large phase 3 clinical trials of tolvaptan in early and later stages of ADPKD. Their design was based on preliminary studies informing on the pharmacokinetics, pharmacodynamics, short-term safety and self-reported tolerability in patients with ADPKD...
October 12, 2018: Nephrology, Dialysis, Transplantation
Nikki Tirada, Mireille Aujero, Gauri Khorjekar, Stephanie Richards, Jasleen Chopra, Sergio Dromi, Olga Ioffe
An understanding of prognostic factors in breast cancer is imperative for guiding patient care. Increased tumor size and more advanced nodal status are established independent prognostic factors of poor outcomes and are incorporated into the American Joint Committee on Cancer (AJCC) TNM (primary tumor, regional lymph node, distant metastasis) staging system. However, other factors including imaging findings, histologic evaluation results, and molecular findings can have a direct effect on a patient's prognosis, including risk of recurrence and relative survival...
October 12, 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
J A Walsh, A B Gottlieb, B Hoepken, T Nurminen, P J Mease
The above article originally published with an error present in Discussion section and presented correctly in this article. The original article was corrected.
October 11, 2018: Clinical Rheumatology
Petra Hissink Muller, Danielle M C Brinkman, Dieneke Schonenberg-Meinema, Wytse Bastiaan van den Bosch, Yvonne Koopman-Keemink, Isabel C J Brederije, Peter W Bekkering, Taco W Kuijpers, Marion Van Rossum, Lisette Wa van Suijlekom-Smit, J Merlijn van den Berg, Stefan Boehringer, Cornelia F Allaart, R Ten Cate
QUESTION: Which is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)? METHODS: In a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease...
October 11, 2018: Annals of the Rheumatic Diseases
Maura C O'Leary, Xiaobin Lu, Ying Huang, Xue Lin, Iftekhar Mahmood, Donna Przepiorka, Denise Gavin, Shiowjen Lee, Ke Liu, Bindu George, Wilson Bryan, Marc R Theoret, Richard Pazdur
Tisagenlecleucel (Kymriah, Novartis Pharmaceuticals, East Hanover, NJ) is a CD19-directed genetically-modified autologous T-cell immunotherapy. On August 30, 2017, the U.S. Food and Drug Administration approved tisagenlecleucel for treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Approval was based on the complete remission (CR) rate, durability of CR and minimal residual disease (MRD) < 0.01% in a cohort of 63 children and young adults with relapsed or refractory ALL treated on a single-arm trial (CCTL019B2202)...
October 11, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Glenville Jones, Martin Kaufmann
Ever since the metabolism of vitamin D was elucidated in the early 1970s, organic chemists and pharmacologists have sought to design and synthesize vitamin D analogs that would mimic some, if not all, of the biological actions of the parent vitamin. Thousands of molecules have been prepared and tested but only a few of these have been successfully translated into marketed drug forms that can be used to treat bone disease or in other areas of clinical medicine. These synthetic vitamin D analogs have been reviewed extensively in recent years [1-5] and this chapter will not attempt to duplicate those reviews...
October 11, 2018: British Journal of Clinical Pharmacology
Natalia Valencia-Enciso, Carlos O Mendivil
Disorders of lipid and lipoprotein metabolism play a central role in the pathogenesis of atherosclerotic cardiovascular diseases (CVDs). Despite the widespread use of efficacious lipid-modifying therapies, the residual risk of CVD remains unacceptably high. The purpose of this manuscript is to review the application of new technologies in the treatment of lipid disorders. New therapies work mostly at the gene expression level and are, therefore, different from traditional small-molecule drugs that work mainly by inhibiting already synthesized proteins...
2018: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
Annika Steffen, Jakob Holstiege, Kerstin Klimke, Manas K Akmatov, Jörg Bätzing
This study aimed at providing a current and nearly complete picture of the patterns of the initiation of disease-modifying antirheumatic drugs (DMARDs) in patients with newly diagnosed RA. Based on ambulatory drug prescription data and physician billing claims data covering 87% of the German population, we assembled a cohort of incident RA patients aged 15-79 years (n = 54,896) and assessed the prescription frequency of total DMARDs, conventional synthetic (csDMARDs) and biologic DMARDs (bDMARDs) within the first year of disease...
October 10, 2018: Rheumatology International
Hooi-Yeen Yap, Sabrina Zi-Yi Tee, Magdelyn Mei-Theng Wong, Sook-Khuan Chow, Suat-Cheng Peh, Sin-Yeang Teow
Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission...
October 9, 2018: Cells
Na Li, Mei-Hao Xiang, Jin-Wen Liu, Hao Tang, Jian-Hui Jiang
Spherical nucleic acid (SNA) constructs are promising new single entity materials, which possess significant advantages in biological applications. Current SNA-based drug delivery system typically employed single-layered ss- or ds-DNA as the drug carriers, resulting in limited drug payload capacity and disease treatment. To advance corresponding applications, we developed a novel DNA-programmed polymeric SNA, a long concatamer DNA polymer that is uniformly distributed on gold nanoparticles (AuNPs), by self-assembling from two short alternating DNA building blocks upon initiation of immobilized capture probes on AuNPs, through a supersandwich hybridization reaction...
October 10, 2018: Analytical Chemistry
Milan Stoiljkovic, Craig Kelley, Tamas L Horvath, Mihály Hajós
BACKGROUND: Translational research in Alzheimer's disease (AD) pathology provides evidence that accumulation of amyloid-β and hyperphosphorylated tau, neuropathological hallmarks of AD, is associated with complex disturbances in synaptic and neuronal function leading to oscillatory abnormalities in the neuronal networks that support memory and cognition. Accordingly, our recent study on transgenic TgF344-AD rats modeling AD showed an age-dependent reduction of stimulation-induced oscillations in the hippocampus, and disrupted long-range connectivity together with enhanced neuronal excitability in the cortex, reflected in greatly increased expression of high-voltage spindles, an epileptic absence seizure-like activity...
October 10, 2018: Alzheimer's Research & Therapy
Asma Elmabruk, Banibrata Das, Deepthi Yedlapudi, Liping Xu, Tamara Antonio, Maarten E A Reith, Aloke K Dutta
We have developed a series of carbazole-derived compounds based on our hybrid D2/D3 agonist template to design multifunctional compounds for the symptomatic and disease-modifying treatment of Parkinson's disease (PD). The lead molecules (-)-11b, (-)-15a and (-)-15c exhibited high affinity for both D2 and D3 receptors where as in GTPγS functional assay, the compounds showed potent agonist activity at both D2 and D3 receptors (EC50 (GTPγS); D2 = 48.7 nM, D3 = 0.96 nM for 11b, D2 = 0.87 nM, D3 = 0.23 nM for 15a and D2 = 2...
October 9, 2018: ACS Chemical Neuroscience
Rosa Pennisi, Jacopo Albanesi, Paolo Ascenzi, Clara Nervi, Alessandra di Masi
Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy characterized by the expansion of hematopoietic stem/progenitor cells (HPCs) blocked at different stages of maturation/differentiation. The poor outcome of AMLs necessitates therapeutic improvement. In AML, genes encoding for myeloid transcription factors, signaling receptors regulating cell proliferation, and epigenetic modifiers can be mutated by somatically acquired genetic mutations or altered by chromosomal translocations. These mutations modify chromatin organization at genes sites regulating HPCs proliferation, terminal differentiation, and DNA repair, contributing to the development and progression of the disease...
October 8, 2018: IUBMB Life
Vappu Rantalaiho, Tia Sandström, Juhani Koski, Pekka Hannonen, Timo Möttönen, Kaipiainen-Seppänen Oili, Timo Yli-Kerttula, Markku J Kauppi, Toini Uutela, Timo Malmi, Heikki Julkunen, Leena Laasonen, Hannu Kautiainen, Marjatta Leirisalo-Repo
OBJECTIVE: The short-term outcomes of remission-targeted treatments of rheumatoid arthritis (RA) are well-established, but the long-term success of such strategies is speculative, as is the role of early add-on biologics. We assessed the 10-year outcomes of patients with early RA treated with initial remission-targeted triple combination of conventional synthetic disease-modifying antirheumatic-drugs (csDMARDs), 7.5 mg prednisolone (PRD) and additional infliximab or placebo infusions...
October 8, 2018: Arthritis Care & Research
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