Biologics Target bad Bugs

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Hello my dear Pharmainfo friends, I take this marked space to present my blog entry over this topic. What are bad bugs and why to target bag bugs? Infectious diseases account for almost 25% of mortality and morbidity and are emerging as the second most common cause of deaths worldwide as reported by World Health Organization survey [1]. Therefore, there is a need of hour to address the pathogens responsible for such infinite mortality and morbidity rates. FDA categorized bad bugs or pathogenic microorganisms and toxins under six categories of Pathogenic Bacteria, Enterovirulent Escherichia Coli group, Parasitic protozoa and worms, Viruses, Natural Toxins and Other pathogenic agents like Prions [2]. Common infectious diseases include respiratory tract infections like pneumococcal infections, tuberculosis, influenza, HIV/AIDS, diarrhoeal diseases, malaria and deadly bacterial infections of the blood or the brain, causing septicaemia and meningitis[3]. Therefore, prescribing antibiotics has become a "weapon in hands" for RMP's owing to 40% of pharma market, which is poised to grow at the rate of 70% by the year 2017, while assessing the resistance of antibiotics has become a "challenge" to Pharmacists. It is a pungent fact to be agreed that "miracle drugs" which made life easier are not effective all the times and 70 percent of infections are resistant to at least one drug [4]. Therefore, wetting up the dried pipeline of pharma industry, came the concept of targeting the bad bugs especially bacterial bugs causing deaths of 90,000 of people every year. Several attempts made to overcome the problem of bacterial resistance to infectious diseases includes Antivirulence strategies, Antimicrobial peptides, Bacteriophages, Making use of functional genomics and novel screening methods to find new targets, Potentiators of currently used antibiotics, Screening natural products, Therapeutic antibodies and Vaccines. Among the fore mentioned attempts "therapeutic antibodies" (Targeted monoclonal antibodies) has grabbed immense attention owing to advantages of specificity towards particular antigen, non-destruction of commensal flora (otherwise leading to obesity and cancer) and produced against any pathogen [1,5]. Background and Clinical Potentials: Antibacterial antibodies may be categorized based on their mechanism of action as those that directly bind to pathogens, target toxins, or virulence factors and are developed against Staphylococcus Aureus[1]. Ongoing Research: Only palivizumab (Synagis), a humanized mAb directed against respiratory syncytial virus (RSC) has been approved in the treatment of premature infants and infants with bronchopulmonary dysplasia and others are under the phases of clinical and preclinical trials [6]. Most of antibodies have failed due to lack of efficacy in Phase II/Phase III trials, which include veronate developed by Inhibitex of USA against Staphylococcus infections [7,8]. Kenta biotech has publication regarding Phase I study of KBPA101, Pseudomonas monoclonal, that has extended its research against Staphylococci and Acinetobacter [9, 10]. Biosynexus's of USA developed Pagibaximab, monoclonal against Staphylococci infections, which is under Phase II/III trials. It targets lipoteichoic acid (LTA) and causes destruction in the cell walls of Gram-positive bacteria through phagocytosis [5,11,12]. Anthim, ABthrax and Valortim are in clinical trials developed against B.anthracis toxins by research based-companies Elusys, HGS and Medarex of USA [13,14,15,16,17]. Antibody against Shigatoxin-producing E.coli is under clinical trials developed by Thallion Company of Canada and Saul Tzipori of USA [18,19,20,21]. Antibodies for treatment of cystic fibrosis are also marketed by Immune system AB against Pseudomonas and anti-type secretion antibody against Pseudomonas by Kalobios of USA, which is under clinical trails [22,23,24]. Conclusion & Future Prospectives: Today thousand deaths occurred...tomorrow ten thousand and the epidemic continues to climb??? Being a Pharmacist, it is our shoulder pain to avert this catastrophe.... Can we do this??? Think... Rethink... And the answer is "Yes" if we act now. Therefore, it becomes mandatory for the research scholars to focus on the issue as Joseph R. Dalovisio said "As Antibiotic Discovery Stagnates... A Public Health Crisis Brews" " Infectious diseases physicians are alarmed by the prospect that effective antibiotics may not be available to treat seriously ill patients in the near future. There simply aren't 't enough new drugs in the pharmaceutical pipeline to keep pace with drug-resistant bacterial infections, so-called ' super bugs". Focused Research in Biologics are predicted to open new vistas in the treatment of viral infections and bacterial toxins and use of two or more antibodies along with antibiotics evidenced by C. difficile is going to bash the rising pharma markets in profits owing for enhanced therapeutic efficacy [5, 25]. The topic may seem simple, but yet the issue to be raised. "This blog does not include plagiarized material". Acknowledgements: I thank pharmainfo.net, our leader Dr.Lakshmi, my beloved friends Shravani, Anand Kumar and last but not the least blog readers for their valuable comments. Bibliography: 1. Bad bugs Future drugs. Vinnova: Innovations under development that can supplement traditional use of antibiotics; [Undated; Uncited ]. Available from: www.vinnova.se/upload/Bad Bugs Future drugs.pdf [Accessed on March11, 2010]. 2. U.S.Food and Drug Administration: Center for Food Safety & Applied Nutrition. The Bad Bug Book: Food borne Pathogenic Microorganisms and Natural Toxins Handbook; [Updated 2006 Apr 25; Uncited]. Available from: www.fda.gov [Accessed on March 12, 2010]. 3. Centers for Disease Control and Prevention. Atlanta: Emerging infectious diseases; [Undated; Uncited]. Department of Health and Human Services; [About 24 screens]. Available from: http://www.cdc.gov/ncidoc/eid [Accessed on March13, 2010]. 4. Infectious Diseases Society of America. Alexandria: Infectious Diseases Society of America; c2009 [Updated 2004 July; Uncited ]. Available from: www.idsociety.org [Accessed on March13, 2010]. 5. Andy E. Nature Review Drug Discovery: Biologics target bad bugs. Macmillan Publishers Limited. 2010 March; pp. 177-178:9. Available from: www.nature.com/reviews/drugdisc [Accessed on March14, 2010]. 6. Bebbington, C.; Yarranton, G. Antibodies for the treatment of bacterial infections: current experience and future prospects. Curr Opin Biotechnol. 2008, 19, 613-9. 7. Domanski, P.J.; Patel, P.R.; Bayer, A.S. Characterization of a humanized monoclonal antibody recognizing clumping factor A expressed by Staphylococcus aureus. Infect Immun. 2005, 73, 5229-32. 8. Inhibitex. Alpharetta: Developing differentiated anti-infectives for today's unmet medical needs; c2007 [Updated 2010 March; Uncited]. Available from: www.inhibitex.com [Accessed on March14, 2010].

9. Lazar, H.; Horn, M.P.; Zuercher, A.W. Pharmacokinetics and safety profile of the human anti P. aeruginosa serotype O11 IgM monoclonal antibody KBPA-101 in healthy volunteers. Antimicrob Agents Chemother. 2009.

10. Kentabiotech. Berne: Pioneering antibody therapies for life threatening infections; [Undated; Uncited]. Available from: www.kentabiotech.com [Accessed on March15, 2010].

11.Walsh, S.; Kokai-Kun, J.; Shah, A.; Mond, J. Extended nasal residence time of lysostaphin and an anti-staphylococcal monoclonal antibody by delivery in semisolid or polymeric carriers. Pharm Res. 2004, 21, 1770-5. 12. Biosynexus. Developing novel approaches to prevent and treat life threatening bacterial infections; c 2002-2009 [Undated; Uncited]. Available from: www.biosynexus.com [Accessed on March15, 2010].

13. Mohamed, N.; Clagett, M.; Li, J. A high-affinity monoclonal antibody to anthrax protective antigen passively protects rabbits before and after aerosolized Bacillus anthracis spore challenge. Infect Immun. 2005, 73, 795-802. 14. Vitale, L.; Blanset, D.; Lowy, I. Prophylaxis and therapy of inhalational anthrax by a novel monoclonal antibody to protective antigen that mimics vaccine-induced immunity. Infect Immun. 2006, 74, 5840-7. 15. Elusys. Elusys Therapeutics, Inc; c 2010 [Undated; Uncited]. Available from: www.elusys.com [Accessed on March16, 2010].

16. Medarex. Medarex Bristol-Myers Squibb; c 2001-2009 [Undated; Uncited]. Available from: www.medarex.com [Accessed on March16, 2010].

17. Human Genome Sciences. Rockville: Great Science. Great Medicine. Creating Breakthrough Treatments; c 2010 [Updated 2010 March; Uncited].Available from: www.hgsi.com [Accessed on March16, 2010]. 18.Thallion. Thallion Pharma; c 1998-2007 [Updated 2010 March; Uncited]. Available from: www.thallion.com [Accessed on March16, 2010].

19. Mukherjee, J.; Chios, K.; Fishwild, D. Production and characterization of protective human antibodies against Shiga toxin 1. Infect Immun. 2002, 70, 5896-9. 20. Mukherjee, J.; Chios, K.; Fishwild, D. Human Stx2-specific monoclonal antibodies prevent systemic complications of Escherichia coli O157:H7 infection. Infect Immun. 2002, 70, 612-9. 21. Bitzan, M.; Poole, R.; Mehran, M. Safety and Pharmacokinetics of Chimeric Anti-Shiga Toxin 1 and Anti-Shiga Toxin 2 Monoclonal Antibodies in Healthy Volunteers. Antimicrob Agents Chemother. 2009. 22. Immune System. Immune System Overview; c 2009 [Undated; Uncited]. Available from: www.immunesystem.com [Accessed on March17, 2010]. 23. Baer, M.; Sawa, T.; Flynn, P. An engineered human antibody fab fragment specific for Pseudomonas aeruginosa PcrV antigen has potent antibacterial activity. Infect Immun. 2009, 77, 1083-90. 24. Kalobios. Kalobios Pharmaceuticals; c 2010 [Undated; Uncited]. Available from: www.kalobios.com [Accessed on March17, 2010].

25. Janter, M. Monoclonal antibodies for prophylaxis and therapy of infectious diseases. 2007 Nov [cited 2009 Nov 1]; 12(4):525-540: [about 1 p.]. Available from: http://informahealthcare.com/loi/emd [Accessed on March17, 2010].

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