Potential new drugs for human African trypanosomiasis: some progress at last

Barrett, M. P. (2010) Potential new drugs for human African trypanosomiasis: some progress at last. Current Opinion in Infectious Diseases, 23(6), pp. 603-608. (doi:10.1097/QCO.0b013e32833f9fd0)

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Publisher's URL: http://dx.doi.org/10.1097/QCO.0b013e32833f9fd0

Abstract

Purpose of review: This review covers recent developments towards novel treatments for human African trypanosomiasis (HAT).

Recent findings: Within the past decade, some important advances in the treatment of HAT have been made. One old drug, melarsoprol, previously administered over a period of a month or more, is now given in a 10-day regimen greatly reducing hospital costs. A combination chemotherapy, eflornithine alongside nifurtimox, has been introduced to decrease the time frame and overall dosing of eflornithine and reducing the risk of drug resistance emerging. One new, orally available diamidine prodrug, pafuramidine, that recently completed phase III clinical trials, disappointingly was halted in its progress to clinic when unforeseen toxicity issues emerged. The diamidine series, however, has recently yielded representatives that cure second-stage central nervous system (CNS)-involved infections in experimental animals while showing less tissue accumulation in mammals and thus offer considerable promise. A nitroheterocycle, fexinidazole, whose trypanocidal activity was first shown nearly 30 years ago, has entered clinical trials. Another approach, grounded in the use of pharmacokinetic data, has brought another new class of compound based on the oxaborole scaffold forward for clinical candidacy. Furthermore, several target-based and whole organism-based chemical compound screening campaigns have identified promising hits for lead development.

Summary: The new developments in trypanocidal drug discovery mean that new compounds could become available within the next 5 years to support the WHO declared campaign to eliminate HAT.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barrett, Professor Michael
Authors: Barrett, M. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Current Opinion in Infectious Diseases
Publisher:Lippincott Williams & Wilkins
ISSN:0951-7375
ISSN (Online):1473-6527

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
522031In vivo imaging models of African trypanosomiasis to support drug discovery programmes.Michael BarrettGates Foundation (GATES)OPPGH5337III - PARASITOLOGY
471291Drug resistance in African trypanosomesHarry De KoningMedical Research Council (MRC)G0701258III - PARASITOLOGY