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MOLECULES OF THE MILLENNIUM
Year : 2005  |  Volume : 37  |  Issue : 1  |  Page : 47
 

Mycograb®: Human recombinant antibody to HSP90


Dept. of Pharmacology and Therapeutics, Goa Medical College, Bambolim, Goa - 403 202, India

Correspondence Address:
A Garg
Dept. of Pharmacology and Therapeutics, Goa Medical College, Bambolim, Goa - 403202
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.13860

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How to cite this article:
Garg A, Rataboli P V. Mycograb®: Human recombinant antibody to HSP90. Indian J Pharmacol 2005;37:47

How to cite this URL:
Garg A, Rataboli P V. Mycograb®: Human recombinant antibody to HSP90. Indian J Pharmacol [serial online] 2005 [cited 2019 May 25];37:47. Available from: http://www.ijp-online.com/text.asp?2005/37/1/47/13860


Systemic infection by Candida species in the United States still tags with it a significant 35-40% mortality rate and data does not look better in any other part of the world either.[1],[2] This high rate despite the advances in antifungal treatment can be attributed to non-Candida albicans Candida species and their growing resistance to commonly used antifungal drugs.[3],[4]

This has resulted in a thrust to produce newer and more powerful drugs and drug delivery systems giving birth to variconazole, pneumocandins like caspofungin acetate, ABCL (Amphotericin-B Lipid Complex), ABCD (Amphotericin-B Colloid Dispersion), AmBisome (Unilamellar vesicle formulation of amphotericin-B), and lyophilized powders.

In fungal infections, and especially deep-seated systemic infections, heat shock protein 90 (HSP90) plays a crucial role and is essential for the viability of the yeast.[5] Considering this, a new molecule is developed called Mycograb ® (Neu Tec Pharma plc).[6] Mycograb ® is a polyhistidine tagged purified human recombinant antibody to HSP90. It is the first human recombinant antibody fragment to be used in fungal infections.[7] In the pre-clinical studies it was found to be highly effective when used in combination with amphotericin-B and showed significant antifungal activity against all five species of Candida, namely C. albicans, C. krusei, C. tropicalis, C. parapsilosis, and C. glabrata. However, when combined with fluconazole, it did not increase the response rate in fluconazole-resistant species but increased the clearance of fluconazole-sensitive species of Candida.[8]

Phase I clinical trials began in December 2000 with five patients of systemic candidiasis. The drug was given intravenously and safety assessment, kinetic, and dynamic parameters were studied. Results of these data were first presented at the American Society of Microbiologists Annual Conference, 2001. After confirming the favorable side-effect profile in July 2001, the drug entered Phase II trials. It was a double-blind randomized controlled trial involving 60 patients with culture-confirmed systemic candidiasis. The results were so encouraging that the company was hopeful of getting Phase III waiver from the United States Food and Drug Administration (US FDA) and directly marketing the drug. In January 2003, the Multi Research Ethical Committee (MREC) approved the drug to be tested in the UK and in February of the same year, the company filed the Investigational New Drug (IND) application with FDA. Mycograb ® has been granted the status of orphan drug in Europe and the US by the European Medicine Evaluation Agency (EMEA) and the US FDA respectively.

The time has come to look beyond the physical molecules for the treatment of various infections and to search for some ways to produce biological agent which can take care of biology itself. Mycograb ® is a major leap ahead in this field and like all other drugs it brings with it two hopes: first, it will be useful for the prophylaxis and treatment of systemic candidiasis, and second, that it could be of immense help in overcoming the growing resistance against antifungal agents.

 
 » References Top

1.McNeil MM, Nash SL, Hajjeh RA, Phelan MA, Conn LA, Plikaytis BD, et al. Trends in mortality due to invasive mycotic diseasea in United States, 1980-1997. Clin Infect Dis 2001;33:641-7.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Narang A, Agarwal PB, Chakrabarti A, Kumar P. Epidemiology of systemic candidiasis in tertiary care neonatal unit. J Trop Pediatr 1998;44:104-8.  Back to cited text no. 2    
3.Krcmery V, Barnes AJ. Non-albicans Candida spp. causing fungaemia: Pathogenicity and antifungal resistance. J Hosp Infect 2002;50:243-60.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Hope W, Morton A, Eisen DP. Increase in prevalence of nosocomial non-Candida albicans candidaemia and the association of Candida krusei with fluconazole use. J Hosp Infect 2002;50:56-65.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Porsius JC, van Vliet HJA, van Zeijl HJ, Goessens WHF, Michel MF. Detection of an antibody response in immunocompetent patients with systemic candidiasis or Candida albicans colonisation. Eur J Clin Microbiol Infect Dis 1990;9:352-5.  Back to cited text no. 5    
6.Mycograb® available on http://81.201.142.226/companyInfo/history.asp. Accessed on 20th October 2004.  Back to cited text no. 6    
7.Burnie J, Matthews RC. Genetically recombinant antibodies: New therapeutics against candidiasis. Expert Opin Biol Ther 2004;4:233-41.  Back to cited text no. 7    
8.Matthews RC, Rigg G, Hodgetts S, Carter T, Chapman C, Gregory C, et al. Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90. Antimicrob Agents Chemothr 2003;47:2208-16.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]



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2 Evaluation of the IgY production against Hsp90 of Candida albicans
T. Ziglari,A.R. Khosravi,H. Tadjbdkhsh,F. Asadi,M. Modirsaneii,H. Shokri,G.R. Nikbakhtborojeni,M. Rostamibeshman
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