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Paul M. Ridker is a cardiovascular epidemiologist and biomedical researcher. He is currently the Eugene Braunwald Professor of Medicine at Harvard University and Brigham and Women's Hospital, where he directs the Center for Cardiovascular Disease Prevention. Ridker also holds an appointment as Professor in the Department of Epidemiology at the Harvard T.H. Chan School of Public Health.
A CETP inhibitor is a member of a class of drugs that inhibit cholesterylester transfer protein (CETP). They are intended to reduce the risk of atherosclerosis by improving blood lipid levels. At least three medications within this class have failed to demonstrate a beneficial effect.
Reslizumab, sold under the brand names Cinqair and Cinqaero, is a humanized monoclonal antibody against human interleukin-5 (IL-5). Reslizumab binds specifically to IL-5, a key cytokine responsible for the differentiation, maturation, recruitment and activation of human eosinophils. By binding to human IL-5, it blocks its biological function; consequently survival and activity of eosinophils are reduced. The benefits with reslizumab are its ability to reduce the exacerbation rate and improve lung function and asthma-related quality of life in patients with severe eosinophilic asthma and with at least one previous asthma exacerbation in the preceding year. The most common side effects are increased blood creatine phosphokinase, myalgia and anaphylactic reactions.
Priliximab is a human-mouse chimeric anti-CD4 monoclonal antibody. It has been tested on patients with Crohn's disease and multiple sclerosis but has not yet received U.S. Food and Drug Administration licensing. The patent belongs to the biotechnology company Centocor.
Canakinumab, sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis, active Still's disease, including adult-onset Still's disease, gout flares. It is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha.
Tanox was a biopharmaceutical company based in Houston, Texas. The company was founded by two biomedical research scientists, Nancy T. Chang and Tse Wen Chang in March 1986 with $250,000, which was a large part of their family savings at that time. Both Changs grew up and received college education in chemistry in National Tsing Hua University in Taiwan and obtained Ph.D. degrees from Harvard University. For postdoctoral training, Tse Wen shifted to immunology and did research with Herman N. Eisen at the Center for Cancer Research, M.I.T. The two Changs successively became research managers and worked with a range of monoclonal antibody projects in Centocor, Inc. based in Malvern, Pennsylvania, from 1981 to 1985. The Changs were recruited by Baylor College of Medicine toward the end of 1985 and offered faculty positions in the Division of Molecular Virology. Soon after their arrival, they were encouraged by a high-ranking Baylor official and local business leaders to start a biotech venture in Houston. This was in a period of time when the economy of Houston was in slump as the result of the collapse of the oil industry.
Lebrikizumab, sold under the brand name Ebglyss is a humanized monoclonal antibody used for the treatment of atopic dermatitis.
Tesofensine (NS2330) is a serotonin–noradrenaline–dopamine reuptake inhibitor from the phenyltropane family of drugs, which is being developed for the treatment of obesity. Tesofensine was originally developed by a Danish biotechnology company, NeuroSearch, who transferred the rights to Saniona in 2014.
Pitrakinra is a 15-kDa human recombinant protein of wild-type human interleukin-4 (IL-4). It is an IL-4 and IL-13 antagonist that has been studied in a phase IIb clinical trial for the treatment of asthma. Two point mutations on pitrakinra confer its ability to block signaling of IL-4 and interleukin-13 (IL-13) by preventing assembly of IL-4 receptor alpha (IL-4Rα) with either IL-2Rγ or IL-13Rα. Upregulation of Th2 cytokines, including IL-4 and IL-13, is thought to be critical for the allergic inflammation associated with atopic diseases such as asthma and eczema. The targets of pitrakinra action are inflammatory cells and structural cells that express IL-4Rα. The drug has been applied both as a subcutaneous injection and as an inhalation, but the latter formulation proved to be more effective.
Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene.
Dalcetrapib is a CETP inhibitor which was being developed by Hoffmann–La Roche until May 2012. The drug was aimed at raising the blood levels of HDL cholesterol. Prevailing observations indicate that high HDL levels correlate with better overall cardiovascular health, though it remains unclear whether raising HDL levels consequently leads to an increase in cardiovascular health.
Siltuximab (INN), sold under the brand name Sylvant, is used for the treatment of people with multicentric Castleman's disease. It is a chimeric monoclonal antibody that binds to interleukin-6. It is an interleukin-6 (IL-6) antagonist.
Clazakizumab, an investigational drug, is an aglycosylated, humanized rabbit monoclonal antibody against interleukin-6. Clazakizumab was developed by Bristol Myers Squib and Alder Biopharmaceuticals. A preliminary randomized, double-blind, placebo-controlled, phase 2 dose-ranging study of clazakizumab in psoriatic arthritis patients, funded by the manufacturer, suggested that clazakizumab may be an effective treatment option for musculoskeletal aspects of psoriatic arthritis; however, the antibody lacked a dose-response effect.
Ixekizumab, sold under the brand name Taltz, is an injectable medication for the treatment of autoimmune diseases. Chemically, it is a form of a humanized monoclonal antibody. The substance acts by binding interleukin 17A and neutralizing it, reducing inflammation.
Olokizumab (OKZ) sold under the name Artlegia, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis and COVID-19. It is a humanized monoclonal antibody against the interleukin-6 (IL-6). IL-6 is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases. Olokizumab is the first interleukin-6 (IL-6) inhibitor approved for treatment of rheumatoid arthritis which blocks directly cytokine instead of its receptor. Olokizumab specifically binds to IL-6 at Site 3, blocking IL-6 ability to form hexameric complex. Olokizumab was developed by R-Pharm group, and was launched in 2020.
Ocaratuzumab is a humanized monoclonal antibody designed for the treatment of cancer and autoimmune disorders. The antibody is engineered for enhanced affinity to the CD20 antigen on B-lymphocytes, increased antibody-dependent cell-mediated cytotoxicity (ADCC), and for improved treatment of low-affinity FcγRIIIa allotypes.
Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody blocking interleukin 4 and interleukin 13, used for allergic diseases such as atopic dermatitis (eczema), asthma and nasal polyps which result in chronic sinusitis. It is also used for the treatment of eosinophilic esophagitis and prurigo nodularis.
Tildrakizumab, sold under the brand names Ilumya and Ilumetri, is a monoclonal antibody designed for the treatment of immunologically mediated inflammatory disorders. It is approved for the treatment of adult patients with moderate-to-severe plaque psoriasis in the United States and the European Union.
Risankizumab, sold under the brand name Skyrizi, is a humanized monoclonal antibody used for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease. It is designed to target interleukin 23A (IL-23A). It is given by subcutaneous injection.
A cholesterol crystal is a solid, crystalline form of cholesterol found in gallstones and atherosclerosis. Gallstones occurring in industrialized societies typically contain more than 70-90% cholesterol by weight, much of which is crystalline. Cholesterol crystals are a hallmark of atherosclerosis, which is believed to be an early cause of atherosclerotic inflammation. Cholesterol phase transition from liquid to crystalline form is linked to inflammation. Cholesterol crystals are believed to induce inflammation by activation of the NLRP3 inflammasome.
References
- ↑ Wada, Yukihiro; Jensen, Camilla; Meyer, Anna Sina Pettersson; Zonoozi, Amir Abbas Mohseni; Honda, Hirokazu (October 2023). "Efficacy and safety of interleukin-6 inhibition with ziltivekimab in patients at high risk of atherosclerotic events in Japan (RESCUE-2): A randomized, double-blind, placebo-controlled, phase 2 trial". Journal of Cardiology. 82 (4): 279–285. doi: 10.1016/j.jjcc.2023.05.006 . PMID 37211246.
- ↑ Adamstein, Nicholas H.; Cornel, Jan Hein; Davidson, Michael; Libby, Peter; de Remigis, Alessandra; Jensen, Camilla; Ekström, Kathrine; Ridker, Paul M (1 February 2023). "Association of Interleukin 6 Inhibition With Ziltivekimab and the Neutrophil-Lymphocyte Ratio: A Secondary Analysis of the RESCUE Clinical Trial". JAMA Cardiology. 8 (2): 177–181. doi: 10.1001/jamacardio.2022.4277 . PMC 9713672 . PMID 36449307.
- ↑ Pergola, Pablo E.; Devalaraja, Matt; Fishbane, Steven; Chonchol, Michel; Mathur, Vandana S.; Smith, Mark T.; Lo, Larry; Herzog, Kurt; Kakkar, Rahul; Davidson, Michael H. (January 2021). "Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial". Journal of the American Society of Nephrology. 32 (1): 211–222. doi: 10.1681/ASN.2020050595 . PMC 7894678 . PMID 33272965.
- ↑ Ridker, Paul M; Devalaraja, Matt; Baeres, Florian M M; Engelmann, Mads D M; Hovingh, G Kees; Ivkovic, Milana; Lo, Larry; Kling, Douglas; Pergola, Pablo; Raj, Dominic; Libby, Peter; Davidson, Michael (May 2021). "IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial". The Lancet. 397 (10289): 2060–2069. doi:10.1016/S0140-6736(21)00520-1. PMID 34015342. S2CID 235073253.
- ↑ Wada, Y; Jensen, C; Meyer, S; Yamamoto, Y; Honda, H (3 October 2022). "Effects of interleukin-6 inhibition with ziltivekimab in patients at high risk of atherosclerotic events in Japan: results from the phase 2 RESCUE-2 trial". European Heart Journal. 43 (Supplement_2). doi: 10.1093/eurheartj/ehac544.2618 .
- ↑ Adamstein, N; Cornel, J; Davidson, M; Libby, P; De Remigis, A; Jensen, C; Rajan, S; Ridker, P (3 October 2022). "The effect of ziltivekimab on the neutrophil-lymphocyte ratio: analysis from RESCUE". European Heart Journal. 43 (Supplement_2). doi: 10.1093/eurheartj/ehac544.2290 .
- ↑ Nowak, Kristen L.; Kakkar, Rahul; Devalaraja, Matt; Lo, Larry; Park, Wansu; Gobburu, Joga; Kling, Douglas; Davidson, Michael; Chonchol, Michel (February 2021). "A Phase 1 Randomized Dose-Escalation Study of a Human Monoclonal Antibody to IL-6 in CKD". Kidney360. 2 (2): 224–235. doi: 10.34067/KID.0005862020 . PMC 8741001 . PMID 35373026.