Pharmacogenomics: will the promise be fulfilled?

Tools such as genome resequencing and genome-wide association studies have recently been used to uncover a number of variants that affect drug toxicity and efficacy, as well as potential drug targets. But how much closer are we to incorporating pharmacogenomics into routine clinical practice? Five experts discuss how far we have come, and highlight the technological, informatics, educational and practical obstacles that stand in the way of realizing genome-driven medicine.     

Evolutionary physiology at 30+: Has the promise been fulfilled?

Three decades ago, interactions between evolutionary biology and physiology gave rise to evolutionary physiology. This caused comparative physiologists to improve their research methods by incorporating evolutionary thinking. Simultaneously, evolutionary biologists began focusing more on physiological mechanisms that may help to explain constraints on and trade-offs during microevolutionary processes, as well as macroevolutionary patterns in physiological diversity. Here we argue that evolutionary physiology has yet to reach its full potential, and propose new avenues that may lead to unexpected advances. Viewing physiological adaptations in wild animals as potential solutions to human diseases offers enormous possibilities for biomedicine. New evidence of epigenetic modifications as mechanisms of phenotypic plasticity that regulate physiological traits may also arise in coming years, which may also represent an overlooked enhancer of adaptation via natural selection to explain physiological evolution. Synergistic interactions at these intersections and other areas will lead to a novel understanding of organismal biology.     

The promise of e-Health – a Canadian perspective

Canadians value their health care system above any other social program. Canada's system of health care faces significant financial and population pressures, relating to cost, access, quality, accountability, and the integration of information and communication technologies (ICTs). The health-system also faces certain unique challenges that include care delivery within a highly decentralised system of financing and accountability, and care delivery to a significant portion of the population sparsely distributed across a landmass of 10 million square kilometres, in areas of extreme climatic conditions. All of these challenges are significant catalysts in the development of technologies that aim to significantly mitigate or eliminate these selfsame challenges.The system is undergoing widespread review, nationally, and within each province and territory, where the bulk of care provision is financed and managed. The challenges are being addressed by national, regional and provincial initiatives in the public, private and not-for-profit sectors.The promise of e-Health lies in the manner and degree to which it can mitigate or resolve these challenges to the health system and build on advancements in ICTs supporting the development of a health infostructure. Canada is actively developing and implementing technological solutions to deliver health information and health care services across the country. These solutions, while exciting and promising, also present new challenges, particularly in regard to acceptable standards, choice of technologies, overcoming traditional jurisdictional boundaries, up-front investment, and privacy and confidentially.Many organisations and governments are working to address these challenges. The Canadian Institute for Health Information (CIHI) will play an increasingly significant role in these initiatives, as the management of health information becomes a more crucial factor in the successful delivery of health care services in the new millennium.     

Cell therapy: Promise fulfilled?

Cellular immunotherapy has been widely accepted as a new powerful modality of cancer treatment. The last 2 decades have seen impressive results in its application against haemato-oncologic malignancies, melanomas and prostate carcinoma. Cellular immunotherapy has since found applicability beyond cancer into autoimmunity and continues to expand in its clinical applicability. The discovery that stem cells have the ability to differentiate into more mature cell types, like neurones and myocardium, has focused research on using exogenous cells to repair damaged tissues. This led to numerous clinical trials using stem cells in myocardial infarction, cardiomyopathy and spinal cord damage. Results have ranged from modest to significant clinical outcomes with continuing debate on the exact process of regeneration achieved. The intertwining between cell therapy and transfusion medicine now includes research on progenitor cells for the production of mature red cells. It is also clear that cell therapy has enabled an improved understanding of the pathogenesis and clinical course of many diseases, while perhaps its role in regenerative medicine is most enticing. However, the critical role of manufacturing in terms of cost, complexity, reproducibility, and regulatory matters remains a central issue in the consideration of whether cell therapy has met all of its promise.     

Holistic frailty prevention: The promise of movement-based mind–body therapies

Aging is characterized by fundamental cellular and molecular hallmarks that result in physiologic decline of most body systems. This may culminate in frailty, a state of decreased reserve. Because frailty is a state of multisystem dysregulation, multimodal interventions may be necessary to mitigate and prevent progression rather than interventions targeting a single system. Movement-based mind–body therapies, such as tai chi and yoga, are promising multimodal strategies for frailty prevention and treatment given their inherent multicomponent nature. In this review, we summarize the links between hallmarks of aging and frailty and how tai chi and yoga may impact these hallmarks. We review trial evidence for the impact of tai chi and yoga on frailty in older populations and discuss opportunities for future research.     

Organ transplantation--how much of the promise has been realized?

Since the introduction of organ transplantation into medical practice, progress and optimism have been abundant. Improvements in immunosuppressive drugs and ancillary care have led to outstanding short-term (1--3-year) patient and graft survival rates. This success is mitigated by several problems, including poor long-term (>5-year) graft survival rates, the need for continual immunosuppressive medication and the discrepancy between the demand for organs and the supply. Developing methods to induce transplant tolerance, as a means to improve graft outcomes and eliminate the requirement for immunosuppression, and expanding the pool of organs for transplantation are the major challenges of the field.     

The new clinical trials with thiazolidinediones--DREAM, ADOPT, and CHICAGO: promises fulfilled?

PURPOSE OF REVIEW: Despite extensive documentation of their insulin-sensitizing and antihyperglycemic effects, the importance and place of the thiazolidinediones in diabetes management remain unclear. Three new controlled clinical trials of thiazolidinediones offer new information on the clinical utility of these agents. RECENT FINDINGS: During the past year, three new trials of thiazolidinediones were reported. In Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication, rosiglitazone reduced progression to diabetes in prediabetic patients by 60%. A Diabetes Outcome Progression Trial found rosiglitazone to have greater antihyperglycemic durability than metformin and glyburide in patients with recently diagnosed type 2 diabetes. Finally, in the Carotid Intima-media Thickness in Atherosclerosis using Pioglitazone, treatment with pioglitazone in patients with type 2 diabetes slowed progression of carotid wall thickness compared with the sulfonylurea glimepiride. SUMMARY: These trials support the contention that thiazolidinediones have superior efficacy in improving and stabilizing glycemic control than older antihyperglycemic agents, especially early in the course of type 2 diabetes. Findings from the Carotid Intima-media Thickness in Atherosclerosis using Pioglitazone add to the evidence that these agents have clinically meaningful vasculoprotective effects. Although generally well tolerated, they promote weight gain, limiting their acceptability to some extent, and occasionally lead to a diagnosis of heart failure, mostly in susceptible individuals.     

Apoptosis in the treatment of cancer: a promise kept?

A common feature of cancer cells is their ability to evade apoptosis as a result of alterations that block cell death signaling pathways. The extensive research efforts that elucidated these signaling pathways over the past decade have set the stage for the development of therapeutic agents that either kill cancer cells selectively or reset their apoptotic threshold. Over the past two years a number of these agents have been evaluated in preclinical and clinical trials. The results of these studies suggest that it might soon be possible to modulate apoptosis in cancer cells for therapeutic benefit.     

The Ascent of Man?

Anyone who cares about the moral and social implications of genomics, genetic engineering and biotechnology should read Michael J. Sandel's article, 'The Case Against Perfection', in the April 2004 issue of The Atlantic Monthly.