Virtual drug discovery and development for neglected diseases through public–private partnerships

Nwaka, Solomon; Ridley, Robert G.

doi:10.1038/nrd1230

Cited by 227 publications

(180 citation statements)

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“…Furthermore, both drugs cause several side effects that contribute to their reduced use in clinical medicine (Cançado 1985). Thus, new compounds are needed to develop more effective medicines to treat Chagas disease, espe- cially in its chronic phase, is needed (Schmidt & KrauthSiegel 2002, Nwaka & Ridley 2003. However, due to low profit prospects, the development of new trypanocidal drugs is not attractive to the pharmaceutical industry (Nwaka & Ridley 2003).…”

mentioning

confidence: 99%

“…Thus, new compounds are needed to develop more effective medicines to treat Chagas disease, espe- cially in its chronic phase, is needed (Schmidt & KrauthSiegel 2002, Nwaka & Ridley 2003. However, due to low profit prospects, the development of new trypanocidal drugs is not attractive to the pharmaceutical industry (Nwaka & Ridley 2003). Thus, this endeavor is being conducted mainly in academic laboratories (Fairlamb 1999).…”

mentioning

confidence: 99%

“…cially in its chronic phase, is needed (Schmidt & KrauthSiegel 2002, Nwaka & Ridley 2003. However, due to low profit prospects, the development of new trypanocidal drugs is not attractive to the pharmaceutical industry (Nwaka & Ridley 2003).…”

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confidence: 99%

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A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation

Cota

Rosa

Fagundes

et al. 2008

Mem. Inst. Oswaldo Cruz

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The fungus Lentinus strigosus (Pegler 1983) (Polyporaceae, basidiomycete) was selected in a screen for inhibitory activity on Trypanosoma cruzi trypanothione reductase (TR). The crude extract of L. strigosus was able to completely inhibit TR at 20 µg/ml. Two triquinane sesquiterpenoids (dihydrohypnophilin and hypnophilin), in addition to two panepoxydol derivatives (neopanepoxydol and panepoxydone), were isolated using a bioassay-guided fractionation protocol. Hypnophilin and panepoxydone displayed IC 50 values of 0.8 and 38.9 µM in the TR assay, respectively, while the other two compounds were inactive. The activity of hypnophilin was confirmed in a secondary assay with the intracellular amastigote forms of T. cruzi, in which it presented an IC 50 value of 2.5 µM. Quantitative flow cytometry experiments demonstrated that hypnophilin at 4 µM also reduced the proliferation of human peripheral blood monocluear cells (PBMC) stimulated with phytohemaglutinin, without any apparent interference on the viability of lymphocytes and monocytes. As the host immune response plays a pivotal role in the adverse events triggered by antigen release during treatment with trypanocidal drugs, the ability of hypnophilin to kill the intracellular forms of T. cruzi while modulating human PBMC proliferation suggests that this terpenoid may be a promising prototype for the development of new chemotherapeutical agents for Chagas disease. Key words: fungal natural products -Chagas disease -drug discovery -immunomodulators -BasidiomycotaChagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects millions of people in Latin America, having an enormous economic and social impact in the endemic areas. These patients rely on treatment with nitrofuran (nifurtimox; Bayer) or nitroimidazol (benznidazole; Roche), medicines that display little or no activity in chronic infections, in spite of their beneficial effect during the acute phase of the disease (Cançado 2002, Coura & Castro 2002. However, significant differences in the therapeutic effectiveness are observed between these two drugs, especially when considering distinct geographical areas, which is probably due to the occurrence of naturally resistant and susceptible T. cruzi strains (Filardi & Brener 1987, Toledo et al. 2003. Furthermore, both drugs cause several side effects that contribute to their reduced use in clinical medicine (Cançado 1985). Thus, new compounds are needed to develop more effective medicines to treat Chagas disease, espe- cially in its chronic phase, is needed (Schmidt & KrauthSiegel 2002, Nwaka & Ridley 2003. However, due to low profit prospects, the development of new trypanocidal drugs is not attractive to the pharmaceutical industry (Nwaka & Ridley 2003). Thus, this endeavor is being conducted mainly in academic laboratories (Fairlamb 1999).Among the many different strategies for drug discovery, screening the local biodiversity for bioactive natural products using appropriate bioassays is an interesting alternative for researchers in affec...

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A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation

Cota

Rosa

Fagundes

et al. 2008

Mem. Inst. Oswaldo Cruz

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“…Their discovery and development are withheld and not made available (Kettler et al 2003). For example the research for a vaccine against AIDS is seen as an important public service; the industry however is uncertain as to whether the investment for the research and development of a new effective vaccine can be amortised, since they must carry the risk of writing off the costs of failure (Brown 2008;Nwaka and Ridley 2003;Ziemba 2005). Furthermore, even if an effective vaccine should be discovered, the private sector cannot be sure that a sufficient number of financially strong markets exist to buy the product, thereby justifying their development and marketing investments.…”

Section: Ppp Application Areasmentioning

confidence: 99%

Public–private partnership as a solution for integrating genetic services into health care of countries with low and middle incomes

2012

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In recent years scientific progress has dramatically raised the potential of genetic services, but the actual benefits of these developments are not universally shared. In countries of low and middle incomes, improvements in genetic services frequently lag behind. Since this is generally caused by lack of resources and not by the lack of political will, the question arises, how can one most easily acquire the necessary capital to improve the health care in these areas. Public-private partnerships (PPPs) offer one approach to solve this issue, aiming at the inclusion of private enterprises in the realisation of public authority services. So far PPPs have been used exclusively in other health service areas. In this paper a first attempt is being made to discuss the feasibility of transferring the concept of PPP to genetic services, and consideration is given as to where the most promising starting point might be. We start by defining a multilevel structure that needs to be considered in providing comprehensive genetic care. We continue by explaining the concept of PPPs and their current types of implementation in medical services. We then examine how the PPP model could be applied to genetic services or sections thereof. We arrive at the conclusion that a likely starting point for PPP in genetic services is at the level of the infrastructure building service.Increasing genetic proficiency and transforming genetic services into practice

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“…Virtual drug-discovery networks 8 for infectious diseases prevalent in the developing world are already functioning on a small scale. Various researchers and institutes are called on by public-private partnerships to contribute their diverse expertise, technology and resources for a limited duration.…”

Section: Making Global Network Workmentioning

confidence: 99%

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Nwaka

2007

Nature

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Virtual drug discovery and development for neglected diseases through public–private partnerships

Cited by 227 publications

References 42 publications

A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation

A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation

Public–private partnership as a solution for integrating genetic services into health care of countries with low and middle incomes

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