Drug discovery and development for neglected diseases: the DNDi model

Abstract

New models of drug discovery have been developed to overcome the lack of modern and effective drugs for neglected diseases such as human African trypanosomiasis (HAT; sleeping sickness), leishmaniasis, and Chagas disease, which have no financial viability for the pharmaceutical industry. With the purpose of combining the skills and research capacity in academia, pharmaceutical industry, and contract researchers, public-private partnerships or product development partnerships aim to create focused research consortia that address all aspects of drug discovery and development. These consortia not only emulate the projects within pharmaceutical and biotechnology industries, eg, identification and screening of libraries, medicinal chemistry, pharmacology and pharmacodynamics, formulation development, and manufacturing, but also use and strengthen existing capacity in disease-endemic countries, particularly for the conduct of clinical trials. The Drugs for Neglected Diseases initiative (DNDi) has adopted a model closely related to that of a virtual biotechnology company for the identification and optimization of drug leads. The application of this model to the development of drug candidates for the kinetoplastid infections of HAT, Chagas disease, and leishmaniasis has already led to the identification of new candidates issued from DNDi's own discovery pipeline. This demonstrates that the model DNDi has been implementing is working but its DNDi, neglected diseases sustainability remains to be proven.

Keywords: Chagas disease; R&D; human African trypanosomiasis; lead optimization; leishmaniasis; product development partnerships; screening.

Figure 1

DNDi portfolio as of January 2010. Abbreviations: R: research, LS: lead selection, LO: lead optimisation, CDRI: Central Drug Research Institute (India), CDCO: Centre for Drug Candidate Optimisation (Australia), FUOP: Federal University of Ouro Preto (Brazil), GNF: Genomics Institute of the Novartis Research Foundation, NITD: Novartis Institute for Tropical Diseases, GATB: Global Alliance for TB Drug Development, LSHTM: London School of Hygiene & Tropical Medicine.

Figure 2

DNDi’s drug discovery process with decision-making tools and key decision points. Abbreviations: ADME, absorbtion-distribution-metabolison-excretion; DDM, drug discovery manual; TPP, target product profile; DMPK, distribution-metabolison-pharmacecotinetic.