Four lessons from global health drug discovery: medicine for an ailing industry?
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ABSTRACT:
SUBMITTER: Elliott RL
PROVIDER: S-EPMC4025862 | biostudies-other | 2012 Sep
REPOSITORIES: biostudies-other
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Project description:Global health networks, webs of individuals and organizations with a shared concern for a particular condition, have proliferated over the past quarter century. They differ in their effectiveness, a factor that may help explain why resource allocations vary across health conditions and do not correspond closely with disease burden. Drawing on findings from recently concluded studies of eight global health networks-addressing alcohol harm, early childhood development (ECD), maternal mortality, neonatal mortality, pneumonia, surgically-treatable conditions, tobacco use, and tuberculosis-I identify four challenges that networks face in generating attention and resources for the conditions that concern them. The first is problem definition: generating consensus on what the problem is and how it should be addressed. The second is positioning: portraying the issue in ways that inspire external audiences to act. The third is coalition-building: forging alliances with these external actors, particularly ones outside the health sector. The fourth is governance: establishing institutions to facilitate collective action. Research indicates that global health networks that effectively tackle these challenges are more likely to garner support to address the conditions that concern them. In addition to the effectiveness of networks, I also consider their legitimacy, identifying reasons both to affirm and to question their right to exert power.
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Project description:Analysis of binding energy hot spots at protein surfaces can provide crucial insights into the prospects for successful application of fragment-based drug discovery (FBDD), and whether a fragment hit can be advanced into a high-affinity, drug-like ligand. The key factor is the strength of the top ranking hot spot, and how well a given fragment complements it. We show that published data are sufficient to provide a sophisticated and quantitative understanding of how hot spots derive from a protein 3D structure, and how their strength, number, and spatial arrangement govern the potential for a surface site to bind to fragment-sized and larger ligands. This improved understanding provides important guidance for the effective application of FBDD in drug discovery.
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Project description:Organisation EGAO00000000867
| EGAO00000000867 | EGA
Project description:The development of structure-guided drug discovery is a story of knowledge exchange where new ideas originate from all parts of the research ecosystem. Dorothy Crowfoot Hodgkin obtained insulin from Boots Pure Drug Company in the 1930s and insulin crystallization was optimized in the company Novo in the 1950s, allowing the structure to be determined at Oxford University. The structure of renin was developed in academia, on this occasion in London, in response to a need to develop antihypertensives in pharma. The idea of a dimeric aspartic protease came from an international academic team and was discovered in HIV; it eventually led to new HIV antivirals being developed in industry. Structure-guided fragment-based discovery was developed in large pharma and biotechs, but has been exploited in academia for the development of new inhibitors targeting protein-protein interactions and also antimicrobials to combat mycobacterial infections such as tuberculosis. These observations provide a strong argument against the so-called 'linear model', where ideas flow only in one direction from academic institutions to industry. Structure-guided drug discovery is a story of applications of protein crystallography and knowledge exhange between academia and industry that has led to new drug approvals for cancer and other common medical conditions by the Food and Drug Administration in the USA, as well as hope for the treatment of rare genetic diseases and infectious diseases that are a particular challenge in the developing world.
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Project description:ContextIn recent decades, natural products have undisputedly played a leading role in the development of novel medicines. Yet, trends in the pharmaceutical industry at the level of research investments indicate that natural product research is neither prioritized nor perceived as fruitful in drug discovery programmes as compared with incremental structural modifications and large volume HTS screening of synthetics.AimWe seek to understand this phenomenon through insights from highly experienced natural product experts in industry and academia.MethodWe conducted a survey including a series of qualitative and quantitative questions related to current insights and prospective developments in natural product drug development. The survey was completed by a cross-section of 52 respondents in industry and academia.ResultsOne recurrent theme is the dissonance between the perceived high potential of NP as drug leads among individuals and the survey participants' assessment of the overall industry and/or company level strategies and their success. The study's industry and academic respondents did not perceive current discovery efforts as more effective as compared with previous decades, yet industry contacts perceived higher hit rates in HTS efforts as compared with academic respondents. Surprisingly, many industry contacts were highly critical to prevalent company and industry-wide drug discovery strategies indicating a high level of dissatisfaction within the industry.ConclusionsThese findings support the notion that there is an increasing gap in perception between the effectiveness of well established, commercially widespread drug discovery strategies between those working in industry and academic experts. This research seeks to shed light on this gap and aid in furthering natural product discovery endeavors through an analysis of current bottlenecks in industry drug discovery programmes.
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Project description:BackgroundSecondary fungal metabolites are important sources for new drugs against infectious diseases and cancers.MethodsTo obtain a library with enough diversity, we collected about 2,395 soil samples and 2,324 plant samples from 36 regions in Africa, Asia, and North America. The collection areas covered various climate zones in the world. We examined the usability of the global fungal extract library (GFEL) against parasitic malaria transmission, Gram-positive and negative bacterial pathogens, and leukemia cells.ResultsNearly ten thousand fungal strains were isolated. Sequences of nuclear ribosomal internal transcribed spacer (ITS) from 40 randomly selected strains showed that over 80% were unique. Screening GFEL, we found that the fungal extract from Penicillium thomii was able to block Plasmodium falciparum transmission to Anopheles gambiae, and the fungal extract from Tolypocladium album was able to kill myelogenous leukemia cell line K562. We also identified a set of candidate fungal extracts against bacterial pathogens.
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Project description:Shifting patterns of tobacco production and consumption, and the resultant disease burden worldwide since the late twentieth century, prompted efforts to strengthen global health governance through adoption of the Framework Convention on Tobacco Control. While the treaty is rightfully considered an important achievement, to address a neglected public health issue through collective action, evidence suggests that tobacco industry globalization continues apace. In this article, we provide a systematic review of the public health literature and reveal definitional and measurement imprecision, ahistorical timeframes, transnational tobacco companies and the state as the primary units and levels of analysis, and a strong emphasis on agency as opposed to structural power. Drawing on the study of globalization in international political economy and business studies, we identify opportunities to expand analysis along each of these dimensions. We conclude that this expanded and interdisciplinary research agenda provides the potential for fuller understanding of the dual and dynamic relationship between the tobacco industry and globalization. Deeper analysis of how the industry has adapted to globalization over time, as well as how the industry has influenced the nature and trajectory of globalization, is essential for building effective global governance responses. This article is published as part of a thematic collection dedicated to global governance.
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Project description:BackgroundSimulation based medical education (SBME) allows learners to acquire clinical skills without exposing patients to unnecessary risk. This is especially applicable to Emergency Medicine training programs where residents are expected to demonstrate proficiency in the management of time critical, low frequency, and highly-morbidity conditions. This study aims to describe the process through which a SBME curriculum was created, in a limited simulation resource setting at a 4-year Emergency Medicine (EM) residency program at the American University of Beirut Medical Center.MethodsA case-based pilot simulation curriculum was developed following Kern's 6 step approach to curriculum design. The curricular objectives were identified through an anonymous survey of the program's residents and faculty. Curriculum outcomes were assessed, and the curriculum was revised to address curricular barriers. Evaluations of the revised curriculum were collected during the simulation sessions and through a whole revised curriculum evaluation at the end of the first year of its implementation.Results14/20 residents (70%) and 8/8 faculty (100%) completed the needs assessment from which objectives for the pilot curriculum were developed and implemented through 6 2-h sessions over a 1-year period. Objectives were not met and identified barriers included cost, scheduling, resources, and limited faculty time. The revised curriculum addressed these barriers and 24 40-min sessions were successfully conducted during the following year. The sessions took place 3 at a time, in 2-h slots, using the same scenario to meet the objectives of the different learners' levels. 91/91 evaluations were collected from participants with overall positive results. The main differences between the pilot and the revised curricula included: a better understanding of the simulation center resources and faculty's capabilities.ConclusionSimulation-based education is feasible even with limited-resources. However, understanding the resources available, and advocating for protected educator time are essential to implementing a successful EM simulation curriculum.
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