“Diabetes and Oral Disease: Implications for Health Professionals” was a one-day conference convened by the Columbia University College of Dental Medicine, the Columbia University College of Physicians and Surgeons, and the New York Academy of Sciences on May 4, 2011in New York City. The program included an examination of the bidirectional relationship between oral disease and diabetes and the inter-professional working relationships for the care of people who have diabetes. The overall goal of the conference was to promote discussion among the healthcare professions who treat people with diabetes, encourage improved communication and collaboration among them and ultimately, improve patient management of the oral and overall effects of diabetes. Attracting over 150 members of the medical and dental professions from eight different countries, the conference included speakers from academia and government and was divided into four sessions. This report summarizes the scientific presentations of the event.
diabetes; oral disease; meeting report
This overview describes the goals and objectives of the second conference conducted as part of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. This second conference was informed by a series of online surveys and brought together basic and clinical scientists from academia and industry to address the concerns central to each field of research. Our goal was to develop recommendations for future research addressing the psychometric and practical challenges involved in translating paradigms from cognitive neuroscience into tasks that are feasible for use in the treatment discovery and development process. In this overview article, we describe the series of talks that were presentations at the conference. This article serves as an introduction to the set of articles included in this special issue that provide overviews and discussions of the issues raised and the recommendations made in these talks and in the subsequent discussions at the meeting. In addition, we describe the online surveys conducted in the month before the conference that were used to obtain suggestions from the field as to important task selection criteria and to generate initial benchmark goals for psychometric development for cognitive neuroscience tasks.
treatment; translation; pharmacology
Academia should be willing to shoulder some of the responsibility for the current dearth of new therapeutic drugs. Our research funding is predicated on the assumption that it will bring value to society, but our emphasis on scientific specialization hinders our ability to add value when a broader vision is required. A solution is the creation of an academy of science generalists motivated to bring together clinical and basic scientists, academia and the private sector, government legislators and industry. A small investment in academic generalists could yield benefits far beyond its modest cost.
Clinical translational medicine (CTM) is an emerging area comprising multidisciplinary research from basic science to medical applications and entails a close collaboration among hospital, academia and industry.
This Session focused discussing on new models for project development and promotion in translational medicine. The conference stimulated the scientific and commercial communication of project development between academies and companies, shared the advanced knowledge and expertise of clinical applications, and created the environment for collaborations.
Although strategic collaborations between corporate and academic institutions have resulted in a state of resurgence in the market, new cooperation models still need time to tell whether they will improve the translational medicine process.
Translational Research (TR) provides a set of tools and communication context for scientists and clinicians to optimize the drug discovery and development process. In the proceedings of a Princeton conference on this timely topic, the strengths and needs of this developing field were debated. Outcomes and key points from these discussions are summarized in this article which covers the topics of defining what we mean by translational research (both theoretically and in operational terms), ways in which to engender the TR mindset and embed it in organizations such as the pharmaceutical industry in order to optimize the impact of available technologies (including imaging methods), the scientific basis and under-pinnings of TR including genomics knowledge, information sharing, as well as examples of application to drug discovery and development. Importantly, it should be noted that collaborations and communications between the stakeholders in this field, namely academia, industry and regulatory authorities, must be strengthened in order for the promise of TR to be delivered as better therapies to patients.
The Board of Pharmaceutical Sciences (BPS) of the International Pharmaceutical Federation (FIP) has developed a view on the future of pharmaceutical sciences in 2020. This followed an international conference with invited participants from various fields (academicians, scientists, regulators, industrialists, venture capitalists) who shared their views on the forces that might determine how the pharmaceutical sciences will look in 2020. The commentary here provides a summary of major research activities that will drive drug discovery and development, enabling technologies for pharmaceutical sciences, paradigm shifts in drug discovery, development and regulations, and changes in education to meet the demands of academia, industry and regulatory institutions for pharmaceutical sciences in 2020.
Electronic supplementary material
The online version of this article (doi:10.1007/s11095-009-0048-3) contains supplementary material, which is available to authorized users.
Pharmaceutical Sciences in 2020
The American Association of Pharmaceutical Scientists (AAPS) National Biotechnology Conference Short Course “Translational Challenges in Developing Antibody-Drug Conjugates (ADCs),” held May 24, 2012 in San Diego, CA, was organized by members of the Pharmacokinetics, Pharmacodynamics and Drug Metabolism section of AAPS. Representatives from the pharmaceutical industry, regulatory authorities, and academia in the US and Europe attended this short course to discuss the translational challenges in ADC development and the importance of characterizing these molecules early in development to achieve therapeutic utility in patients. Other areas of discussion included selection of target antigens; characterization of absorption, distribution, metabolism, and excretion; assay development and hot topics like regulatory perspectives and the role of pharmacometrics in ADC development. MUC16-targeted ADCs were discussed to illustrate challenges in preclinical development; experiences with trastuzumab emtansine (T-DM1; Genentech) and the recently approved brentuximab vedotin (Adcetris®; Seattle Genetics) were presented in depth to demonstrate considerations in clinical development. The views expressed in this report are those of the participants and do not necessarily represent those of their affiliations.
ADC; pharmacokinetics; linker; trastuzumab emtansine; brentuximab vedotin
Alzheimer’s disease (AD), the most common neurodegenerative disorder of the elderly, ranks third in health care cost after heart disease and cancer. Given the disproportionate aging of the population in all developed countries, the socio-economic impact of AD will continue to rise. Mild cognitive impairment (MCI), a transitional state between normal aging and dementia, carries a 4–6-fold increased risk of future diagnosis of dementia. As complete drug-induced reversal of AD symptoms seems unlikely, researchers are now focusing on the earliest stages of AD where a therapeutic intervention is likely to realize the greatest impact. Recently neuroimaging has received significant scientific consideration as a promising in vivo disease-tracking modality that can also provide potential surrogate biomarkers for therapeutic trials. While several volumetric techniques laid the foundation of the neuroimaging research in AD and MCI, more precise computational anatomy techniques have recently become available. This new technology detects and visualizes discrete changes in cortical and hippocampal integrity and tracks the spread of AD pathology throughout the living brain. Related methods can visualize regionally specific correlations between brain atrophy and important proxy measures of disease such as neuropsychological tests, age of onset or factors that may influence disease progression. We describe extensively validated cortical and hippocampal mapping techniques that are sensitive to clinically relevant changes even in the single individual, and can identify group differences in epidemiological studies or clinical treatment trials. We give an overview of some recent neuroimaging advances in AD and MCI and discuss strengths and weaknesses of the various analytic approaches.
The ability to tackle analysis of the brain at multiple levels simultaneously is emerging from rapid methodological developments. The classical research strategies of “measure,” “model,” and “make” are being applied to the exploration of nervous system function. These include novel conceptual and theoretical approaches, creative use of mathematical modeling, and attempts to build brain-like devices and systems, as well as other developments including instrumentation and statistical modeling (not covered here). Increasingly, these efforts require teams of scientists from a variety of traditional scientific disciplines to work together. The potential of such efforts for understanding directed motor movement, emergence of cognitive function from neuronal activity, and development of neuromimetic computers are described by a team that includes individuals experienced in behavior and neuroscience, mathematics, and engineering. Funding agencies, including the National Science Foundation, explore the potential of these changing frontiers of research for developing research policies and long-term planning.
motor system; mathematical modeling; transformative research neuromorphic chips; hippocampal rhythms; behavior; cognition; engineering
If Malaysia is to become a high-income country by 2020, it will have to transform into a knowledge-based, innovation economy. This goal will be achieved by developing an atmosphere conducive to experimentation and entrepreneurship at home; while reaching out to partners across the globe. One of Malaysia’s newest partnerships is with the New York Academy of Sciences. The Academy has expertise in innovation and higher education and a long history of promoting science, education, and science-based solutions through a global network of scientists, industry-leaders, and policy-makers. Malaysia’s Prime Minister, Dato’ Sri Mohd Najib Tun Abdul Razak, leveraged the Academy’s network to convene a science, technology, and innovation advisory council. This council would provide practical guidance to establish Malaysia as an innovation-based economy. Three initial focus areas, namely palm-oil biomass utilisation, establishment of smart communities, and capacity building in science and engineering, were established to meet short-term and long-term targets.
economic development; international cooperation; knowledge; Malaysia; science; technology; United States
Professor Marthanda Varma Sankaran Valiathan, Fellow of the Royal College of Surgeons, ex President of the Indian National Science Academy, is a reputed cardiac surgeon who made original contributions to cardiology and the development of medical technology. He is widely recognized for his role in pioneering the joint culture of medicine and technology, and laying the foundations for the medical devices industry in India. He has pioneered several scientific studies in the field of Ayurveda and authored several books on the subject. In this free and frank interview he discusses three important phases in his life, and his passion for the convergence of modern biology and Ayurveda as a new discipline of science “Ayurvedic Biology”.
Ayurvedic Biology; Professor Valiathan; interview
This conference was the third in a series focusing on developments in the therapy of rheumatoid arthritis (RA) and other rheumatic conditions with biologicals; in many ways, it was perhaps the best one so far. One strength of the meeting was the mix of scientists from academia and from industry, and of workers in basic science as well as clinical investigators. The risks of inhibition of tumor necrosis factor (TNF) were covered in depth for the first time. A number of putative and actual new targets were presented. An updated consensus document on the use of TNF inhibitors will appear in the near future in the Annals of Rheumatic Diseases, authored by Dan Furst et al.
cytokine biology; cytokine blockade; joint damage; regulatory agents; rheumatic diseases
The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative, funded by an R13 conference grant from the National Institute of Mental Health, has sought to facilitate the translation of measures from the basic science of cognition into practical brain-based tools to measure treatment effects on cognition in schizophrenia. In this overview article, we summarize the process and products of the sixth meeting in this series, which focused on the identification of promising imaging paradigms, based on the measurement of cognitive evoked potentials (event-related potential) of cognition-related time-frequency analyses of the electroencephalography as well as functional magnetic resonance imaging. A total of 23 well-specified paradigms from cognitive neuroscience that measure cognitive functions previously identified as targets for treatment development were identified at the meeting as being recommended for the further developmental work needed in order to validate and optimize them as biomarker measures. Individual paradigms are discussed in detail in 6 domain-based articles in this volume. Ongoing issues related to the development of these and other measures as valid, sensitive and reliable measurement, and assessment tools, as well as the steps necessary for the development of specific measures for use as biomarkers for treatment development and personalized medicine, are discussed.
CNTRICS; cognition; cognitive neuroscience; neuroimaging; biomarker; EEG/ERP; fMRI; schizophrenia
Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal.
The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007–2009 at the behest of the Osteoarthritis Research Society International (OARSI FDA initiative).
This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers.
Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within one to two years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent.
The 6th annual Cancer Vaccines and Immunotherapy Colloquium at Walker's Cay was held under the auspices of the Albert B. Sabin Vaccine Institute on March 10–13, 2004. The Colloquium consisted of a select group of 34 scientists representing academia, biotechnology and pharmaceutical industry. The main goal of this gathering was to promote in a peaceful and comfortable environment exchanges between basic and clinical science. The secondary benefit was to inspire novel bench to bedside ventures and at the same time provide feed back about promising and/or disappointing clinical results that could help re-frame some scientific question or guide the design of future trials. Several topics were covered that included tumor antigen discovery and validation, platforms for vaccine development, tolerance, immune suppression and tumor escape mechanisms, adoptive T cell therapy and dendritic cell-based therapies, clinical trials and assessment of response. Here we report salient points raised by speakers or by the audience during animated discussion that followed each individual presentation.
Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by a constellation of cognitive disturbances, the earliest and most prominent being impaired episodic memory. Episodic memory refers to the memory system that allows an individual to consciously retrieve a previously experienced item or episode of life. Many recent studies have focused on characterizing how AD pathology impacts particular aspects of episodic memory and underlying mental and neural processes. This review summarizes the findings of those studies and discusses the effects of current and promising treatments for AD on episodic memory. The goal of this review is to raise awareness of the strides that cognitive neuroscientists have made in understanding intact and dysfunctional memory. Knowledge of the specific memorial processes that are impaired in AD may be of great value to basic scientists developing novel therapies and to clinical researchers assessing the efficacy of those therapies.
Alzheimer's disease; memory; memory disorder
The discovery of glucocorticoids and their enormous therapeutic benefits led to the use of these compounds as valuable medications for a wide variety of diseases. In 1950 this effort was ushered in by a landmark event—the awarding of the 1950 Nobel Prize in Physiology and Medicine to Drs. Phillip Hench, Edward Kendall, and Tadeus Reichstein. It was Hench who described and researched the successful use of the glucocorticoid, cortisone, and pituitary adrenocorticotrophic hormones to treat rheumatoid arthritis. Significant scientific discovery preceded Hench and colleagues’ efforts, but the revolutionary accumulation of discovery in glucocorticoids since then is one of the unique scientific stories in the history of medicine. The scientific conference upon which this volume is based represents an attempt to convene a state-of-the-science meeting on the current understanding and scientific status of this fascinating, far-reaching, and fast-moving field. This last chapter will summarize the exciting presentations of this 2-day conference.
glucocorticoids; mood; stress; suicidal ideation
In June 2007, the Smith-Lemli-Opitz/RSH Foundation held a scientific conference hosted jointly by Dr. Robert Steiner from Oregon Health & Science University (OHSU) and Dr. Forbes D. Porter from The Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), National Institutes of Health. The main goal of this meeting was to promote interaction between scientists with expertise in cholesterol homeostasis, brain cholesterol metabolism, developmental biology, and oxysterol and neurosteroid biochemistry, clinicians researching and treating patients with Smith-Lemli-Opitz syndrome (SLOS), the patient support organization and families. This report summarizes the presentation and discussions at the conference, represents the conference proceedings, and is intended to foster collaborative research and ultimately improve understanding and treatment of SLOS and other inborn errors of cholesterol synthesis.
Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Working Group on Sarcopenia (a task force consisting of geriatricians and scientists from academia and industry) held on June 7–8, 2011 in Toulouse (France). The meeting was specifically focused at gaining knowledge on the currently available biomarkers (functional, biological, or imaging-related) that could be utilized in clinical trials of sarcopenia and considered the most reliable and promising to evaluate age-related modifications of skeletal muscle. Specific recommendations about the assessment of aging skeletal muscle in older people and the optimal methodological design of studies on sarcopenia were also discussed and finalized. Although the study of skeletal muscle decline is still in a very preliminary phase, the potential great benefits derived from a better understanding and treatment of this condition should encourage research on sarcopenia. However, the reasonable uncertainties (derived from exploring a novel field and the exponential acceleration of scientific progress) require the adoption of a cautious and comprehensive approach to the subject.
Brought together by the newly formed Canadian Academy of Health Sciences (CAHS), recognized national leaders in the 6 health sciences disciplines consider the environment for conducting interdisciplinary health research (IDHR) in Canada. Based on first-hand knowledge and thoughtful reflection, the authors argue that although much progress has been made in support of IDHR in Canada, the practical experience of researchers does not always bear this out. This article examines government, industry and academia to identify the cultural and structural characteristics that demand, promote or prevent IDHR in each sector. At its heart is the question, How can universities best support and enhance IDHR, not only for the benefit of science, but also to meet the growing needs of industry and government for intellectual capital?
Focusing on the predominant health sciences disciplines, the authors define IDHR as a team of researchers, solidly grounded in their respective disciplines, who come together around an important and challenging health issue, the research question for which is determined by a shared understanding in an interactive and iterative process. In addition, they suggest that IDHR is directly linked to translational research, which is the application of basic science to clinical practice and the generation of scientific questions through clinical observation.
This analysis of academic, industry and government sectors is not intended to offer rigorous data on the current state of IDHR in Canada. Rather, the goal is to stimulate research-policy dialogue by suggesting a number of immediate measures that can help promote IDHR in Canada.
Recommended measures to support IDHR are aimed at better resourcing and recognition (by universities and granting agencies), along with novel approaches to training, such as government- and industry-based studentships. In addition, we recommend that professional organizations reconsider their policies on publication and governance. Although intended to maintain professional scopes of practice, these policies also serve to entrench disciplinary boundaries in research.
We conclude by suggesting a number of research questions for a more rigorous assessment of the climate for IDHR in Canada. We call for an inventory and comparative analysis of academic centres, institutes and consortiums in Canada that strive to facilitate IDHR; an examination of the impact of professional organizations on health research, and on IDHR in particular; and a systematic review of research training opportunities that promote IDHR, with a view to identifying and replicating proven models.
The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD and 200 normal controls and $67 million funding was provided by both the public and private sectors including the National Institutes on Aging, thirteen pharmaceutical companies and two Foundations that provided support through the Foundation for NIH (FNIH). This article reviews all papers published since the inception of the initiative and summarizes the results as of February, 2011. The major accomplishments of ADNI have been 1) the development of standardized methods for clinical, magnetic resonance imaging (MRI) and positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a multi-center setting; 2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control, MCI and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β amyloid (Aβ) cascade  and tau mediated neurodegeneration hypotheses for AD while brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; 3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities including MRI, FDG-PET, CSF biomarkers and clinical tests; 4) the development of methods for the early detection of AD. CSF biomarkers, Aβ42 and tau as well as amyloid PET may reflect the earliest steps in AD pathology in mildly or even non-symptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; 5) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Baseline cognitive and/or MRI measures generally predicted future decline better than other modalities whereas MRI measures of change were shown to be the most efficient outcome measures; 6) the confirmation of the AD risk loci CLU, CR1 and PICALM and the identification of novel candidate risk loci; 7) worldwide impact through the establishment of ADNI-like programs in Europe, Asia and Australia; 8) understanding the biology and pathobiology of normal aging, MCI and AD through integration of ADNI biomarker data with clinical data from ADNI to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD thereby advancing efforts to find disease modifying drugs for AD; and 9) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world. The ADNI study was extended by a two year Grand Opportunities grant in 2009 and a renewal of ADNI (ADNI2) in October, 2010 through to 2016, with enrollment of an additional 550 participants.
Tobramycin Inhalation Solution USP (TOBI), a therapy developed to treat lung infections associated with cystic fibrosis (CF), was presented as a demonstration case for collaborative pharmaceutical development at a Clinical and Translational Science Awards Industry Forum on “Promoting Efficient and Effective Collaborations Among Academia, Government, and Industry” held in February 2010. TOBI was developed by PathoGenesis Corporation (Seattle, WA) in collaboration with the academic inventors, the National Institutes of Health, the U.S. Food and Drug Administration, and the CF Foundation. The presenters, representing the academic, industry, and foundation partners, each reviewed the program from their perspectives and identified challenges that existed during the discovery, development, and commercialization of TOBI. The attendees were asked to consider other collaborative opportunities that might have further improved TOBI development, including the optimal roles of the academic researchers, foundations, and other agencies when industry drives development and commercialization decisions.
Approximately five million people suffer with Alzheimer disease (AD) and more than twenty-four million people are diagnosed with AD, pre-senile dementia, and other disorders of cognitive loss worldwide. Furthermore, the annual cost per patient with AD can approach $200,000 with an annual population aggregate cost of $100 billion. Yet, complete therapeutic prevention or reversal of neurovascular injury during AD and cognitive loss is not achievable despite the current understanding of the cellular pathways that modulate nervous system injury during these disorders. As a result, identification of novel therapeutic targets for the treatment of neurovascular injury would be extremely beneficial to reduce or eliminate disability from diseases that lead to cognitive loss or impairment. Here we describe the capacity of intrinsic cellular mechanisms for the novel pathways of erythropoietin and forkhead transcription factors that may offer not only new strategies for disorders such as AD and cognitive loss, but also function as biomarkers for disease onset and progression.
aging; Alzheimer disease; angiogenesis; apoptosis; cognitive loss; diabetes; erythropoietin; forkhead transcription factors; immune system; ischemia; neurodegeneration; oxidative stress; vascular disease; Wnt; wingless
In September of 2011, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross-section of basic scientists, clinicians and representatives from the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), the pharmaceutical industry and private foundations to assess the state of the art in animal studies of Rett syndrome (RTT). The aim of the workshop was to identify crucial knowledge gaps and to suggest scientific priorities and best practices for the use of animal models in preclinical evaluation of potential new RTT therapeutics. This review summarizes outcomes from the workshop and extensive follow-up discussions among participants, and includes: (1) a comprehensive summary of the physiological and behavioral phenotypes of RTT mouse models to date, and areas in which further phenotypic analyses are required to enhance the utility of these models for translational studies; (2) discussion of the impact of genetic differences among mouse models, and methodological differences among laboratories, on the expression and analysis, respectively, of phenotypic traits; and (3) definitions of the standards that the community of RTT researchers can implement for rigorous preclinical study design and transparent reporting to ensure that decisions to initiate costly clinical trials are grounded in reliable preclinical data.
Many people see ageing as a time of cognitive and physical decline. For the past three decades, most scientists and the general public have accepted this negative age-stereotype as the norm, but fortunately this view is now challenged. New findings show that well-being and a positive view of ageing are major protective factors against the effects of age on the organism. These results challenge the scientific studies that place emphasis on the negative side of ageing. This ageism view has been observed in each sphere of science, from genetics to social sciences. Perspectives from each domain are described, and new integrative views of successful ageing are summarized.