Collaborations aim to develop new drugs for neglected tropical diseases

BMJ ◽  
2009 ◽  
Vol 338 (jun29 2) ◽  
pp. b2638-b2638 ◽  
Author(s):  
J. H. Tanne
Keyword(s):  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Tropical Diseases

scholarly journals WIPO Re:Search: Catalyzing Public-Private Partnerships to Accelerate Tropical Disease Drug Discovery and Development

2019 ◽  
Vol 4 (1) ◽  
pp. 53 ◽  
Author(s):  
Cathyryne Manner ◽  
Katy Graef ◽  
Jennifer Dent
Keyword(s):  
Drug Discovery ◽  
Intellectual Property ◽  
Neglected Tropical Diseases ◽  
Tropical Disease ◽  
New Drugs ◽  
World Intellectual Property Organization ◽  
Tropical Diseases ◽  
Middle Income ◽  
Drug Discovery And Development ◽  
Partnership Model

Tropical diseases, including malaria and a group of infections termed neglected tropical diseases (NTDs), pose enormous threats to human health and wellbeing globally. In concert with efforts to broaden access to current treatments, it is also critical to expand research and development (R&D) of new drugs that address therapeutic gaps and concerns associated with existing medications, including emergence of resistance. Limited commercial incentives, particularly compared to products for diseases prevalent in high-income countries, have hindered many pharmaceutical companies from contributing their immense product development know-how and resources to tropical disease R&D. In this article we present WIPO Re:Search, an international initiative co-led by BIO Ventures for Global Health (BVGH) and the World Intellectual Property Organization (WIPO), as an innovative and impactful public-private partnership model that promotes cross-sector intellectual property sharing and R&D to accelerate tropical disease drug discovery and development. Importantly, WIPO Re:Search also drives progress toward the United Nations Sustainable Development Goals (SDGs). Through case studies, we illustrate how WIPO Re:Search empowers high-quality tropical disease drug discovery researchers from academic/non-profit organizations and small companies (including scientists in low- and middle-income countries) to leapfrog their R&D programs by accessing pharmaceutical industry resources that may not otherwise be available to them.

scholarly journals Neglected tropical diseases in Brazil

2009 ◽  
Vol 51 (5) ◽  
pp. 247-253 ◽  
Author(s):  
José Angelo L. Lindoso ◽  
Ana Angélica B.P. Lindoso
Keyword(s):  
Neglected Tropical Diseases ◽  
Clinical Manifestations ◽  
Northern Region ◽  
New Drugs ◽  
World Health ◽  
Tropical Diseases ◽  
The North ◽  
The World ◽  
The Status ◽  
Health Organization

Poverty is intrinsically related to the incidence of Neglected Tropical Diseases (NTDs). The main countries that have the lowest human development indices (HDI) and the highest burdens of NTDs are located in tropical and subtropical regions of the world. Among these countries is Brazil, which is ranked 70th in HDI. Nine out of the ten NTDs established by the World Health Organization (WHO) are present in Brazil. Leishmaniasis, tuberculosis, dengue fever and leprosy are present over almost the entire Brazilian territory. More than 90% of malaria cases occur in the Northern region of the country, and lymphatic filariasis and onchocerciasis occur in outbreaks in a particular region. The North and Northeast regions of Brazil have the lowest HDIs and the highest rates of NTDs. These diseases are considered neglected because there is not important investment in projects for the development of new drugs and vaccines and existing programs to control these diseases are not sufficient. Another problem related to NTDs is co-infection with HIV, which favors the occurrence of severe clinical manifestations and therapeutic failure. In this article, we describe the status of the main NTDs currently occurring in Brazil and relate them to the HDI and poverty.

Targeting pteridine reductase 1 and dihydrofolate reductase: the old is a new trend for leishmaniasis drug discovery

2019 ◽  
Vol 11 (16) ◽  
pp. 2107-2130 ◽  
Author(s):  
Gustavo Machado das Neves ◽  
Luciano P Kagami ◽  
Itamar L Gonçalves ◽  
Vera L Eifler-Lima
Keyword(s):  
Dihydrofolate Reductase ◽  
Drug Targets ◽  
Neglected Tropical Diseases ◽  
Molecular Targets ◽  
New Drugs ◽  
Tropical Diseases ◽  
The World ◽  
Leishmania Spp ◽  
Systemic Manifestations ◽  
Potential Drug Targets

Leishmaniasis is one of the major neglected tropical diseases in the world and it is considered endemic in 88 countries. This disease is transmitted by a Leishmania spp. infected sandfly and it may lead to cutaneous or systemic manifestations. The preconized treatment has low efficacy and there are cases of resistance to some drugs. Therefore, the search for new efficient molecular targets that can lead to the preparation of new drugs must be pursued. This review aims to evaluate both Leishmania enzymes PTR1 and DHFR-TS as potential drug targets, highlight their inhibitors and to discuss critically the use of chemoinformatics to elucidate interactions and propose new molecules against these enzymes.

Methods of macrophages activation and their modulation for the prospection of new antileishmania drugs: a review

2021 ◽  
Vol 37 ◽  
pp. e37077
Author(s):  
Michel Muálem de Moraes Alves ◽  
Daniel Dias Rufino Arcanjo ◽  
Rita Cássia Viana de Carvalho ◽  
Layane Valéria Amorim ◽  
Ingredy Lopes dos Santos ◽  
...  
Keyword(s):  
Immune Response ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Tropical Diseases ◽  
First Line ◽  
Phagocytic Capacity ◽  
Activity Increase ◽  
Parasitic Zoonoses ◽  
Infected Cells ◽  
Cellular Immune

Leishmaniasis are a group of parasitic zoonoses provoked by protozoa from Leishmania genus and belonging to the group of neglected tropical diseases. The search and development for new drugs is necessary not only to investigate the activity against only the parasite, but also to investigate the possible synergistic effect of new drugs with the immune response of the host. In the present review, macrophages are pointed out as potential targets of the investigation of new antileishmanial drugs, and some methodologies in order to assess their activation as response to Leishmania-infected cells are presented. Macrophages are an important role in the cellular immune response, since they are cells from mononuclear phagocytic system, the first line of defense of the host, against parasites from Leishmania genus. Phagocytic capacity, lysosomal activity, increase of nitric oxide and intracellular calcium levels are parameters regarding assessment of macrophages activation which allow them to be more hostile in order to solve the infection and lead the patient to cure. In this context, we bring 19 substances already investigated and that activate macrophages, what makes them promising in the antileishmanial treatment. Therefore, assessment of macrophages activation, are important tools for discovery of immunomodulatory compounds which have potential to act in synergism with host immune response. Such compounds might be promising as monotherapy in the treatment of leishmaniasis, as well as being used as adjuvants in vaccines and/or in combination with conventional drugs.

scholarly journals Cheaper faster drug development validated by the repositioning of drugs against neglected tropical diseases

2015 ◽  
Vol 12 (104) ◽  
pp. 20141289 ◽  
Author(s):  
Kevin Williams ◽  
Elizabeth Bilsland ◽  
Andrew Sparkes ◽  
Wayne Aubrey ◽  
Michael Young ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Boolean Functions ◽  
Neglected Tropical Diseases ◽  
Quantitative Structure Activity Relationship ◽  
New Drugs ◽  
Automation System ◽  
Tropical Diseases ◽  
Standard Drug ◽  
Anti Cancer ◽  
Lead Generation

There is an urgent need to make drug discovery cheaper and faster. This will enable the development of treatments for diseases currently neglected for economic reasons, such as tropical and orphan diseases, and generally increase the supply of new drugs. Here, we report the Robot Scientist ‘Eve’ designed to make drug discovery more economical. A Robot Scientist is a laboratory automation system that uses artificial intelligence (AI) techniques to discover scientific knowledge through cycles of experimentation. Eve integrates and automates library-screening, hit-confirmation, and lead generation through cycles of quantitative structure activity relationship learning and testing. Using econometric modelling we demonstrate that the use of AI to select compounds economically outperforms standard drug screening. For further efficiency Eve uses a standardized form of assay to compute Boolean functions of compound properties. These assays can be quickly and cheaply engineered using synthetic biology, enabling more targets to be assayed for a given budget. Eve has repositioned several drugs against specific targets in parasites that cause tropical diseases. One validated discovery is that the anti-cancer compound TNP-470 is a potent inhibitor of dihydrofolate reductase from the malaria-causing parasite Plasmodium vivax .

scholarly journals Systematic study of triazolyl sterols for the development of new drugs against parasitic Neglected Tropical Diseases.

2021 ◽  
Author(s):  
Exequiel Porta ◽  
Shane Wilkinson ◽  
María Sol Ballari ◽  
Babu Tekwani ◽  
Guillermo Labadie
Keyword(s):  
Mammalian Cells ◽  
Neglected Tropical Diseases ◽  
Selectivity Index ◽  
New Drugs ◽  
Tropical Diseases ◽  
Antiparasitic Activity ◽  
Nanomolar Concentration ◽  
Stereocontrolled Synthesis ◽  
Etiological Agents ◽  
Excellent Selectivity

A series of thirty 1,2,3-triazolylsterols were prepared by a stereocontrolled synthesis and inspired by azasterols with proven antiparasitic activity. Ten of these compounds constitute chimeras/hybrids of AZA and 1,2,3-triazolyl azasterols. The entire library was assayed against the etiological agents of the parasites responsible of kinetoplastid diseases (L. donovani, T. cruzi and T. brucei). Several of the compounds were active at submicromolar/nanomolar concentration with excellent selectivity index, when compared to their activity in mammalian cells. Studies of the physicochemical properties in silico were conducted to rationalize the activities.

scholarly journals Seaweeds to the rescue of forgotten diseases: a review

2019 ◽  
Vol 62 (3) ◽  
pp. 211-226 ◽  
Author(s):  
Yolanda Freile-Pelegrín ◽  
Deniz Tasdemir
Keyword(s):  
Natural Products ◽  
Marine Algae ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Bioactive Molecules ◽  
Current Status ◽  
Tropical Diseases ◽  
Clinical Testing ◽  
The World ◽  
Active Substances

Abstract Neglected tropical diseases (NTDs) are a group of diseases that are predominant in the poorest parts of the world affecting 1.4 billion people. The development of new drugs is urgently needed in order to combat these forgotten diseases. Natural products from marine organisms have been widely explored as a source of new bioactive molecules. However, despite their enormous potential in drug discovery, not even one seaweed-based molecule has entered pre-clinical testing for NTDs. This review gives an overview of the current status of algal natural products against NTDs. The list of compounds is by no means exhaustive, but covers the most important classes of active substances in marine algae against the most studied NTDs.

scholarly journals Collaborative Use Repurposing Engine (CURE): FDA-NCATS/NIH Effort to Capture the Global Clinical Experience of Drug Repurposing to Facilitate Development of New Treatments for Neglected and Emerging Infectious Diseases

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S12-S12 ◽  
Author(s):  
Heather Stone ◽  
Leonard Sacks ◽  
Rosemary Tiernan ◽  
Mili Duggal ◽  
Timothy Sheils ◽  
...  
Keyword(s):  
Clinical Experience ◽  
Health Care Providers ◽  
Neglected Tropical Diseases ◽  
Mobile App ◽  
New Drugs ◽  
Global Network ◽  
Case Report Form ◽  
Tropical Diseases ◽  
Care Providers ◽  
Medical Needs

Abstract Background Repurposing approved products has proven a critical strategy to serve unmet medical needs. Historically, 40% of drugs approved for treatment of tropical diseases were repurposed, including albendazole for echinococcosis and neurocysticercosis, and azithromycin for trachoma. Advantages of repurposing include that approved drugs are well characterized, do not require expensive development programs needed for new drugs, and are frequently active against multiple diseases. Owing to the limited number of drugs approved to treat neglected tropical diseases (NTDs) and emerging or drug-resistant infections, healthcare practitioners use existing drugs in novel ways to treat patients with these conditions. This clinical experience, regardless of whether the outcomes are positive or negative, often is not reported or shared, and the knowledge is therefore lost. Methods FDA and NCATS/NIH have built a pilot program called Collaborative Use Repurposing Engine (CURE) to capture and centralize the global experience of new uses of approved medical products to treat emerging threats, NTDs, and multidrug-resistant organisms. CURE includes a website (https://cure.ncats.io/) and a mobile app (download “PROJECT CURE” at Google Play Store). CURE provides a simple case report form for health care providers to report their experiences, and a collection of cases that have already been reported (including successful and unsuccessful treatments) which they can browse. Healthcare providers who register can also participate in a Treatment Discussion Forum, allowing for engagement with fellow clinicians. CURE could be a global network connecting major treatment centers, academics, private practitioners, government facilities, and other clinicians serving as a means of rapid communication of treatment outcomes between providers treating patients with these conditions. Results See attached screen shots. Conclusion Although this evidence may be insufficient to establish the safety or effectiveness of a new use for an existing product, this clinical experience may provide signals and generate hypotheses for future clinical study. It may allow for rapid identification of promising treatment approaches in urgent situations such as during outbreaks of emerging infectious threats. Disclosures All authors: No reported disclosures.

scholarly journals Computational studies of drug repurposing targeting P-glycoprotein mediated multidrug-resistance phenotypes in agents of neglected tropical diseases

2020 ◽  
Author(s):  
Nivedita Jaishankar ◽  
Sangeetha Muthamilselvan ◽  
Ashok Palaniappan
Keyword(s):  
Multidrug Resistance ◽  
Leishmania Major ◽  
Nearest Neighbor ◽  
Efflux Pump ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
List Type ◽  
Tropical Diseases ◽  
P Glycoprotein ◽  
Query Coverage

ABSTRACTMammalian ABCB1 P-glycoprotein is an ATP- dependent efflux pump with broad substrate specificity associated with cellular drug resistance. Homologous to this role in mammalian biology, the P-glycoprotein of agents of neglected tropical diseases (NTDs) mediates the emergence of multidrug-resistance phenotypes. The clinical and socioeconomic implications of NTDs are exacerbated by the lack of research interest among Big Pharma for treating such conditions. This work aims to characterise P-gp homologues in certain agents of key NTDs, namely Protozoa: Leishmania major, Trypanosoma cruzi;Helminths: Onchocerca volvulus, Schistosoma mansoni.PSI-BLAST searches against the genome of each of these organisms confirmed the presence of P-gp homologues. Each homologue was aligned against five P-gp sequences of known structure, to identify the most suitable template based on sequence homology, phylogenetic nearest neighbor, and query coverage. Antibiotics used in the current line of therapy against each of these pathogens were identified using PubChem and their SMILES structures were converted to PDB using BABEL software. Potential antibiotics to test against the set of FDA-approved antibiotics were identified based on similarity to the chemical class of the known drugs and repurposing of the existing drugs. Docking studies of the respective modelled Pgp structures and the set of antibiotic ligands were carried out using AutoDock and the most tenable target-ligand conformations were assessed. The interacting residues within 4.5 Å of the ligand were identified, and the binding pockets were studied. The relative efficacy of the new drugs and the interacting pump residues were identified. Our studies could lay the foundation for the development of effective synergistic or new therapies against key neglected tropical diseases.

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