Drug Repurposing and Repositioning Workshop Summary (2014) / Chapter Skim
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3 Enabling Tools and Technology
3 Enabling Tools and Technology
Pages 17-30
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From page 17... ...
• Tools such as electronic medical records could be valuable for under standing drug effectiveness, drug safety, and patient outcomes and could improve the statistical power of studies. • High-throughput drug screening technologies are another way to quickly generate new ideas about drug targets.
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From page 18... ...
For more than 2 years Butte's laboratory has been analyzing publicly available gene expression data from individuals with diseases and from healthy controls along with data from biological samples treated with drugs and from untreated samples. By comparing the datasets and using a method based on the Connectivity Map strategy, Butte and his colleagues have been able to identify possible drug targets for diseases of interest (Lamb et al., 2006; Sirota et al., 2011)
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From page 19... ...
, and many other databases. Clinical trial data also will become increasingly available, including data from trials that fail but still yield data useful for drug repositioning.
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Simultaneously, translation was driven by an increase in drug discovery meetings, funding initiatives, compound collections, and screening technologies; the development of new pharmaceutical and biotechnology business models; and activities sponsored by such groups as the Academic Drug Discovery Consortium and the International Chemical Biology Society. Technology-Enabled Repurposing The University of New Mexico School of Medicine has used these new initiatives to move aggressively into drug repurposing by using computer modeling and informatics approaches.
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From page 21... ...
Academicians can play a significant role in contributing to this type of translational research, and resources that support discovery technologies and collaborations among basic scientists and clinicians are helpful in achieving this role. DATA MINING Although drug development is a complex and intricate process, it generally follows one of two basic approaches, explained Lon Cardon, senior vice president of alternative discovery and development at GlaxoSmithKline.
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From page 22... ...
A single drug target may be the focus of five to seven projects looking at different indications, but little may emerge from the efforts. The Potential for Genomics to Guide Repurposing The recent study of genomics has been following what Cardon referred to as the "hype cycle."3 In the early 1990s, many geneticists predicted that genomics would revolutionize medicine by identifying new drug targets and personalizing treatments, but when these predictions did not soon become a reality, the enthusiasm surrounding the field faded.
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From page 23... ...
Industry cannot just support academic researchers and hope that something of value is generated, and academic researchers cannot just look for industrial funds to support what they were already doing. New models are needed that will play to the strengths of pharmaceutical companies, biotechnology companies, academic researchers, venture capitalists, and others, which will require give and take from all sides, Cardon said.
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From page 24... ...
For example, GlaxoSmithKline is evaluating cardiovascular outcomes for patients taking darapladib, an Lp-PLA2 inhibitor used to treat coronary heart disease, for the treatment of atherosclerosis.5 Because the prevalence of a loss-of-function mutation in phospholipase A2, group VII in some Asian populations is more than 10 percent, Cardon suggested that by examining the genotypes in the Kadoorie study and querying corresponding EMRs, useful information about safety and other indications for Lp-PLA2 may be obtained (Jang et al., 2011)
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Overall, the drug screening process identifies interesting molecules and helps build a package that can attract partners to finish the development of the molecules. As an example of new technologies that can advance repurposing, McKew mentioned matrix screening, or mechanism interrogation plates, which searches for drug synergy among compounds with known mechanisms of action.
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The drug received an orphan designation from FDA and the European Medicines Agency in 2013, and a Phase I clinical trial had just begun at the NIH Clinical Center at the time of the workshop, McKew said. The intention, he said, is to put together a package of data and incentives that will motivate a drug developer to take the project forward.
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In addition, the costs of some repurposing candidates can be prohibitive if the originator is not willing to participate by donating the molecule, McKew said. PATIENT-REPORTED DATA Drug repurposing projects have uncovered dysfunction in the clinical research enterprise, said Petra Kaufmann, director of the Office of Clinical Research at the National Institute of Neurological Disorders and Stroke (NINDS)
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From page 28... ...
For example, in some of the projects supported by the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) program at NINDS, researchers are required to involve patients from the beginning of the drug study.6 This bidirectional communication makes research projects more successful and aids in information dissemination.
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One way to overcome the interpretation issues of self-reported data encountered in the ALS efforts is to use a different approach to using social media to learn more about potential treatments, Kaufmann said. In general, she said, patients need more opportunities to participate in working groups, data monitoring boards, and other activities that can speed up drug development.
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