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lupus biologic drug research

Aikaterini Thanou, Joan T Merrill
PURPOSE OF REVIEW: To review progress in the field of clinical trials for SLE. RECENT FINDINGS: Treatment development for SLE has been marked by failures of many later phase studies, representing billions of dollars of lost research and development funding. Recently, more successful Phase II trials have tested reductions in background medications, novel stringent endpoints, and identification of informative immunologic subsets to achieve greater treatment effects...
May 3, 2018: Current Rheumatology Reports
Nirupama Gupta, Cuong Q Nguyen, Renee F Modica, Melissa E Elder, Eduardo H Garin
BACKGROUND: BK virus (BKV) is a ubiquitous polyoma virus that lies dormant in the genitourinary tract once acquired in early childhood. In states of cellular immunodeficiency, the virus can reactivate to cause hemorrhagic cystitis and nephritis. Children with systemic lupus erythematosus (SLE) have an increased risk of developing infectious complications secondary to their immunocompromised state from the administration of several immuno-modulatory drugs. Currently, there are no data regarding the prevalence of BK viruria or viremia in children with SLE...
April 11, 2017: Pediatric Rheumatology Online Journal
R Pikman, S Kivity, Y Levy, M-T Arango, J Chapman, H Yonath, Y Shoenfeld, S G Gofrit
Animal models are a key element in disease research and treatment. In the field of neuropsychiatric lupus research, inbred, transgenic and disease-induced mice provide an opportunity to study the pathogenic routes of this multifactorial illness. In addition to achieving a better understanding of the immune mechanisms underlying the disease onset, supplementary metabolic and endocrine influences have been discovered and investigated. The ever-expanding knowledge about the pathologic events that occur at disease inception enables us to explore new drugs and therapeutic approaches further and to test them using the same animal models...
April 2017: Lupus
Haijing Wu, Jinrong Zeng, Jinghua Yin, Qiao Peng, Ming Zhao, Qianjin Lu
Systemic lupus erythematosus (SLE) is a complex and highly heterogeneous disease, which affects multiple organs, including joints, skin, kidneys, heart, hematopoietic system, and nerve system. While the etiopathogenesis of SLE still remains unclear, genetic susceptibilities and aberrant epigenetic modifications are believed to be involved. For precision therapy, it is necessary to assess accurately and objectively organ involvements and disease activity, which is difficult by current clinical laboratory tests...
April 2017: Autoimmunity Reviews
Maliha F Shaikh, Natasha Jordan, David P D'Cruz
Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease that is highly heterogeneous in its presentation. This can pose significant challenges for physicians responsible for the diagnosis and treatment of such patients. SLE arises from a combination of genetic, epigenetic and environmental factors. Pathologically, the disease is primarily driven by loss of immune tolerance and abnormal B- and T-cell function. Major organ involvement may lead to significant morbidity and mortality. Classification criteria for SLE have been developed largely for research purposes; however, these are also widely used in clinical practice...
February 2017: Clinical Medicine: Journal of the Royal College of Physicians of London
Hongxu Wang, Ju Cao, Xiaofei Lai
Interleukin-34 (IL-34) was initially identified as an alternative ligand for the colony-stimulating factor-1 receptor (CSF-1R) to mediate the biology of mononuclear phagocytic cells. Recently, IL-34 was found to be associated with chronic inflammation, such as in rheumatoid arthritis (RA). Both RA and systemic lupus erythematosus (SLE) are multifactorial autoimmune diseases and are characterized by excessive immune and inflammatory responses. Thus, we investigated whether IL-34 is involved in the pathogenesis of SLE...
December 28, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Rahul Nagar
Autophagy, literally meaning "self-eating," is an intracellular catabolic process of delivering cytosol and/or its specific content to the lysosomes for degradation.The resulting macromolecular constituents are recycled and utilized again by the cells. Basal level autophagy plays an important role in cellular homeostasis through the elimination of the old or damaged organelles, as well as aggregated intracellular proteins. Autophagy refers to sequestration of intact organelles along with a portion of cytosol, into a double-or multi-membrane structure known as phagophore, which elongates, and after closure, forms a vesicular structure known as the autophagosome...
May 2017: Indian Journal of Dermatology, Venereology and Leprology
Brigitte Papahadjopoulos-Sternberg
Freeze-fracture electron microscopy (FFEM) as a cryofixation, replica, and transmission electron microscopy technique is unique in membrane bilayer and lipid monolayer research because it enables us to excess and visualize pattern such as domains in the hydrophobic center of lipid bilayer as well as the lipid/gas interface of lipid monolayer. Since one of the preparation steps of this technique includes fracturing the frozen sample and since during this fracturing process the fracture plane follows the area of weakest forces, these areas are exposed allowing us to explore pattern built up by lipids and/or intrinsic proteins but also initiated by peptides, drugs, and toxins reaching into these normally hard to access areas...
2017: Methods in Molecular Biology
Andrea Doria, M Eric Gershwin, Carlo Selmi
The significant decrease in mortality rates worldwide, the increased proportion of patients achieving a durable remission, and the recent approval of a new drug after several decades are encouraging advances in the tangled history of systemic lupus erythematosus (SLE). However, when data are observed more closely, the research findings on disease pathogenesis and targeted treatments have been quite misleading, as illustrated by the central role of B cells but the missed endpoints in rituximab clinical trials which are burdened by the wide variability of SLE manifestations or the ethnic determinants of disease severity...
November 2016: Journal of Autoimmunity
A Boneparth, S E Wenderfer, L Nandini Moorthy, S M Radhakrishna, A C P Sagcal-Gironella, E von Scheven
Objective The objective of this article is to describe and compare clinical features, treatment, and renal outcomes of children with membranous lupus nephritis (MLN), through analysis of a national multicenter registry. Methods Patients with pediatric systemic lupus erythematosus (SLE) and MLN from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry were included. Demographic, disease and medication-related data were collected between 2010 and 2014 from 59 CARRA Legacy Registry sites...
March 2017: Lupus
K C Kalunian
Clinical trials of investigational agents in systemic lupus erythematosus (SLE) have focused on targeting dysregulated B and T cells; however, recent translational research findings of the importance of the dysregulation of the innate immune system in SLE have led to clinical trials that target interferon. Three biologics that target type I interferons have been tested for their efficacy and safety in active SLE patients; these phase II trials have tested the hypothesis that down-regulation of interferon-regulated gene expression (the interferon signature) lessen the clinical burden of SLE...
September 2016: Lupus
Jorge Medina-Rosas, Hanan Al-Rayes, Ahmed T Moustafa, Zahi Touma
INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting different organs. The improved knowledge of the disease's pathogenesis has contributed to the emergence of immune targets and new biologic drugs directed at them. Although rheumatologists continue to use off-label biologics in SLE resistant to other immunosuppressants, only belimumab has been approved as a biological therapy since 2011. AREAS COVERED: In this review, an overview is provided on: 1) the classification of the biologic drugs in clinical trials and of those under research; 2) the results of clinical trials of biologic therapy with an interpretation of pitfalls and syntheses of potential approaches to overcome these pitfalls and, 3) the commonly used disease activity metrics and composite indices for assessing response to drugs...
October 2016: Expert Opinion on Biological Therapy
Robert A Mook, Jiangbo Wang, Xiu-Rong Ren, Minyong Chen, Ivan Spasojevic, Larry S Barak, H Kim Lyerly, Wei Chen
The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. Niclosamide is a multi-functional drug that possesses important biological activity in addition to inhibition of Wnt/β-catenin signaling...
September 1, 2015: Bioorganic & Medicinal Chemistry
Guixiu Shi, Yuan Liu
No abstract text is available yet for this article.
2014: Current Pharmaceutical Biotechnology
Xiao-Jiaoyang Li, Zhen-Zhou Jiang, Lu-yong Zhang
ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook. f. (Tripterygium wilfordii), also known as Huangteng and gelsemium elegan, is a traditional Chinese medicine that has been marketed in China as Tripterygium wilfordii glycoside tablets. Triptolide (TP), an active component in Tripterygium wilfordii extracts, has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. This review summarizes recent developments in the research on the pharmacodynamics, pharmacokinetics, pharmacy and toxicology of TP, with a focus on its novel mechanism of reducing toxicity...
August 8, 2014: Journal of Ethnopharmacology
Hyoyoung Kim, Won Gi Yoo, Junhyung Park, Heebal Kim, Byeong-Chul Kang
Single-nucleotide polymorphisms (SNPs) have been emerging out of the efforts to research human diseases and ethnic disparities. A semantic network is needed for in-depth understanding of the impacts of SNPs, because phenotypes are modulated by complex networks, including biochemical and physiological pathways. We identified ethnicity-specific SNPs by eliminating overlapped SNPs from HapMap samples, and the ethnicity-specific SNPs were mapped to the UCSC RefGene lists. Ethnicity-specific genes were identified as follows: 22 genes in the USA (CEU) individuals, 25 genes in the Japanese (JPT) individuals, and 332 genes in the African (YRI) individuals...
March 2014: Genomics & Informatics
Sulaiman M Al-Mayouf, Abdullatif Alenazi, Hind AlJasser
OBJECTIVE: To report the indications and safety of biologic agents in childhood rheumatic diseases at a tertiary hospital. METHODS: Children with rheumatic diseases treated with biologic agents at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, from January 2001 to December 2011 were included. All patients were reviewed for: demographic characteristics, diagnosis, concomitant treatment and indications of using biologic agents, age at start of therapy and side effects during the treatment period...
June 2016: International Journal of Rheumatic Diseases
Izabela Kokot, Lilla Pawlik-Sobecka, Sylwia Płaczkowska, Agnieszka Piwowar
Prolactin (PRL) is a hormone synthesized and secreted by lactotroph cells in the anterior pituitary gland. There is also extrapituitary hormone secretion by many cells, including cells of the immune system. In physiological conditions PRL is responsible for lactogenesis and other processes associated with it. PRL plays a significant role during the immune response as a cytokine, affecting proliferation and differentiation of many immune system cells. The biological effect of the hormone depends on binding with the specific prolactin receptor PRL-R, and activation of the transcription factors of targeted genes...
2013: Postȩpy Higieny i Medycyny Doświadczalnej
Frédéric A Houssiau, Bernard R Lauwerys
Despite decades of clinical research aimed at finding the most appropriate immunosuppressive regime, lupus nephritis (LN) remains one of the major disease manifestations of systemic lupus erythematosus (SLE) with a great impact on survival and quality of life. We start this review by defining the disease burden, the real-world challenges and the poor prognostic factors. We then discuss the current anti-inflammatory, cytotoxic and biologic therapies, with special emphasis on the need for optimal global care.
June 2013: Best Practice & Research. Clinical Rheumatology
Geraldina Lionetti, Yukiko Kimura, Laura E Schanberg, Timothy Beukelman, Carol A Wallace, Norman T Ilowite, Jane Winsor, Kathleen Fox, Marc Natter, John S Sundy, Eric Brodsky, Jeffrey R Curtis, Vincent Del Gaizo, Solomon Iyasu, Angelika Jahreis, Ann Meeker-O'Connell, Barbara B Mittleman, Bernard M Murphy, Eric D Peterson, Sandra C Raymond, Soko Setoguchi, Jeffrey N Siegel, Rachel E Sobel, Daniel Solomon, Taunton R Southwood, Richard Vesely, Patience H White, Nico M Wulffraat, Christy I Sandborg
The proven effectiveness of biologics and other immunomodulatory products in inflammatory rheumatic diseases has resulted in their widespread use as well as reports of potential short- and long-term complications such as infection and malignancy. These complications are especially worrisome in children who often have serial exposures to multiple immunomodulatory products. Post-marketing surveillance of immunomodulatory products in juvenile idiopathic arthritis (JIA) and pediatric systemic lupus erythematosus is currently based on product-specific registries and passive surveillance, which may not accurately reflect the safety risks for children owing to low numbers, poor long-term retention, and inadequate comparators...
November 2013: Pediatrics
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