Biomarker-Drug and Liquid Biopsy Co-development for Disease Staging and Targeted Therapy: Cornerstones for Alzheimer's Precision Medicine and Pharmacology.

Systems biology studies have demonstrated that different (epi)genetic and pathophysiological alterations may be mapped onto a single tumor's clinical phenotype thereby revealing commonalities shared by cancers with divergent phenotypes. The success of this approach in cancer based on analyses of traditional and emerging body fluid-based biomarkers has given rise to the concept of liquid biopsy enabling a non-invasive and widely accessible precision medicine approach and a significant paradigm shift in the management of cancer. Serial liquid biopsies offer clues about the evolution of cancer in individual patients across disease stages enabling the application of individualized genetically and biologically guided therapies. Moreover, liquid biopsy is contributing to the transformation of drug research and development strategies as well as supporting clinical practice allowing identification of subsets of patients who may enter pathway-based targeted therapies not dictated by clinical phenotypes alone. A similar liquid biopsy concept is emerging for Alzheimer's disease, in which blood-based biomarkers adaptable to each patient and stage of disease, may be used for positive and negative patient selection to facilitate establishment of high-value drug targets and counter-measures for drug resistance. Going beyond the "one marker, one drug" model, integrated applications of genomics, transcriptomics, proteomics, receptor expression and receptor cell biology and conformational status assessments during biomarker-drug co-development may lead to a new successful era for Alzheimer's disease therapeutics. We argue that the time is now for implementing a liquid biopsy-guided strategy for the development of drugs that precisely target Alzheimer's disease pathophysiology in individual patients

Are providers prepared for genomic medicine: interpretation of Direct-to-Consumer genetic testing (DTC-GT) results and genetic self-efficacy by medical professionals.

BACKGROUND:Precision medicine is set to deliver a rich new data set of genomic information. However, the number of certified specialists in the United States is small, with only 4244 genetic counselors and 1302 clinical geneticists. We conducted a national survey of 264 medical professionals to evaluate how they interpret genetic test results, determine their confidence and self-efficacy of interpreting genetic test results with patients, and capture their opinions and experiences with direct-to-consumer genetic tests (DTC-GT). METHODS:Participants were grouped into two categories, genetic specialists (genetic counselors and clinical geneticists) and medical providers (primary care, internists, physicians assistants, advanced nurse practitioners, etc.). The survey (full instrument can be found in the Additional file 1) presented three genetic test report scenarios for interpretation: a genetic risk for diabetes, genomic sequencing for symptoms report implicating a potential HMN7B: distal hereditary motor neuropathy VIIB diagnosis, and a statin-induced myopathy risk. Participants were also asked about their opinions on DTC-GT results and rank their own perceived level of preparedness to review genetic test results with patients. RESULTS:The rates of correctly interpreting results were relatively high (74.4% for the providers compared to the specialist's 83.4%) and age, prior genetic test consultation experience, and level of trust assigned to the reports were associated with higher correct interpretation rates. The self-selected efficacy and the level of preparedness to consult on a patient's genetic results were higher for the specialists than the provider group. CONCLUSION:Specialists remain the best group to assist patients with DTC-GT, however, primary care providers may still provide accurate interpretation of test results when specialists are unavailable

The Price of Progress: Funding and Financing Alzheimer\u27s Disease Drug Development

Introduction Advancing research and treatment for Alzheimer\u27s disease (AD) and the search for effective treatments depend on a complex financial ecosystem involving federal, state, industry, advocacy, venture capital, and philanthropy funding approaches. Methods We conducted an expert review of the literature pertaining to funding and financing of translational research and drug development for AD. Results The federal government is the largest public funder of research in AD. The National Institute on Aging, National Institute of Mental Health, National Institute of General Medical Sciences, and National Center for Advancing Translational Science all fund aspects of research in AD drug development. Non-National Institutes of Health federal funding comes from the National Science Foundation, Veterans Administration, Food and Drug Administration, and the Center for Medicare and Medicaid Services. Academic Medical Centers host much of the federally funded basic science research and are increasingly involved in drug development. Funding of the “Valley of Death” involves philanthropy and federal funding through small business programs and private equity from seed capital, angel investors, and venture capital companies. Advocacy groups fund both basic science and clinical trials. The Alzheimer Association is the advocacy organization with the largest research support portfolio relevant to AD drug development. Pharmaceutical companies are the largest supporters of biomedical research worldwide; companies are most interested in late stage de-risked drugs. Drugs progressing into phase II and III are candidates for pharmaceutical industry support through licensing, mergers and acquisitions, and co-development collaborations. Discussion Together, the funding and financing entities involved in supporting AD drug development comprise a complex, interactive, dynamic financial ecosystem. Funding source interaction is largely unstructured and available funding is insufficient to meet all demands for new therapies. Novel approaches to funding such as mega-funds have been proposed and more integration of component parts would assist in accelerating drug development

Genomic sequencing capacity, data retention, and personal access to raw data in Europe

Whole genome/exome sequencing (WGS/WES) has become widely adopted in research and, more recently, in clinical settings. Many hope that the information obtained from the interpretation of these data will have medical benefits for patients and—in some cases—also their biological relatives. Because of the manifold possibilities to reuse genomic data, enabling sequenced individuals to access their own raw (uninterpreted) genomic data is a highly debated issue. This paper reports some of the first empirical findings on personal genome access policies and practices. We interviewed 39 respondents, working at 33 institutions in 21 countries across Europe. These sequencing institutions generate massive amounts of WGS/WES data and represent varying organisational structures and operational models. Taken together, in total, these institutions have sequenced ∼317,259 genomes and exomes to date. Most of the sequencing institutions reported that they are able to store raw genomic data in compliance with various national regulations, although there was a lack of standardisation of storage formats. Interviewees from 12 of the 33 institutions included in our study reported that they had received requests for personal access to raw genomic data from sequenced individuals. In the absence of policies on how to process such requests, these were decided on an ad hoc basis; in the end, at least 28 requests were granted, while there were no reports of requests being rejected. Given the rights, interests, and liabilities at stake, it is essential that sequencing institutions adopt clear policies and processes for raw genomic data retention and personal access

Personalized medicine : the impact on chemistry

An effective strategy for personalized medicine requires a major conceptual change in the development and application of therapeutics. In this article, we argue that further advances in this field should be made with reference to another conceptual shift, that of network pharmacology. We examine the intersection of personalized medicine and network pharmacology to identify strategies for the development of personalized therapies that are fully informed by network pharmacology concepts. This provides a framework for discussion of the impact personalized medicine will have on chemistry in terms of drug discovery, formulation and delivery, the adaptations and changes in ideology required and the contribution chemistry is already making. New ways of conceptualizing chemistry’s relationship with medicine will lead to new approaches to drug discovery and hold promise of delivering safer and more effective therapies

Regional science policy and the growth of knowledge megacentres in bioscience clusters

Changes in epistemology in biosciences are generating important spatial effects. The most notable of these is the emergence of a few Bioscience Megacentres of basic and applied bioscience (molecular, post-genomic, proteomics, etc.) medical and clinical research, biotechnology research, training in these and related fields, academic entrepreneurship and commercial exploitation by clusters of drug discovery start-up and spin-off companies, along with specialist venture capital and other innovation system support services. Large pharmaceutical firms that used to lead such knowledge generation and exploitation processes are becoming increasingly dependent upon innovative drug solutions produced in such clusters, and Megacentres are now the predominant source of such commercial knowledge. Big pharma is seldom at the heart of Megacentres such as those the paper will argue are found in about four locations each in the USA and Europe, but remains important for some risk capital (milestone payments), marketing and distribution of drugs discovered. The reasons for this shift (which is also spatial to some extent) are as follows: first, bioscientific research requires the formation of collaboratory relationships among hitherto cognitively dissonant disciplines molecular biology, combinatorial chemistry, high throughput screening, genomics, proteomics and bioinformatics to name a few. Second, the canonical chance discovery model of bioscientific research is being replaced by rational drug design based on those technologies because of the need massively to reduce search costs and delivery timeframes. Third, the US and to some extent European 'Crusade against Cancer' and other pathologies has seen major increases in basic research budgets (e.g. to $27.3 billion in 2003 for the US National Institutes of Health) and foundation expenditure (e.g.$1billion in 2003 by the UK's Wellcome Trust; $1 billion approximately by the top ten US medical foundations, and a comparable sum from corporate foundations). Each of these tendencies weakens the knowledge generation role of 'big pharma'and strengthens that of Megacentres. But the process also creates major, new regional disparities, which some regional governances have recognised, causing them to develop responsibilities for regional science policy and funding to offset spatial biases intrinsic in traditional national (and in the EU, supranational) research funding regimes. Responses follow a variety of models ranging from market following to both regionalised (decentralising by the centre) and regionalist (ground-up), but in each case the role of Megacentres is justified in health terms. But their role in assisting fulfilment of regional economic growth visions is also clearly perceived and pronounced in policy terms.

Consumer acceptance of nutrigenomics based personalised nutrition

Nutrigenomics is a new and promising development in nutritional science which aims to understand the fundamental molecular processes affected by foods. Despite general agreement on its promise for better understanding diet¿health relationships, less consensus exists among experts on the potential of spin-offs aimed at the consumer such as personalised nutrition. Research into consumer acceptance of such applications is scarce. The present study develops a set of key hypotheses on public acceptance of personalised nutrition and tests these in a representative sample of Dutch consumers. An innovative consumer research methodology is used in which consumers evaluate short films which are systematically varied scenarios for the future of personalised nutrition. Consumer evaluations of these films, which are pre-tested in a pilot study, allow a formal test of how consumer perceptions of personalised nutrition drive consumer acceptance and through which fundamental psychological processes these effects are mediated. Public acceptance is enhanced if consumers can make their genetic profile available free at their own choice, if the actual spin-off products provide a clearly recognisable advantage to the consumer, and are easy to implement into the daily routine. Consumers prefer communication on nutrigenomics and personalised nutrition by expert stakeholders to be univocal and aimed at building support with consumers and their direct environments for this intriguing new development. Additionally, an exploratory segmentation analysis indicated that people have different focal points in their preferences for alternative scenarios of personalised nutrition. The insights obtained from the present study provide guidance for the successful further development of nutrigenomics and its applications