Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics) - Volume 11, Issue 4, 2013

This article examines the emerging discipline of food genomics to probe the nature and transmission mechanism of epigenetic changes to the genome related to nutrition, and its impact on policy specifically, and the ethics in 21st century human societies more broadly. The overarching aim is to make recommendations for global health policy that will benefit from advances in personalized genomics knowledge in the context of food. The discussion explores the challenging possibility of intergenerational transfer and retention of environmental signals and imprints on the genome. In addition, the article draws on the socio-ethical aspects of making decisions about how to use that information in order to benefit present and future generations equitably. Personalized nutrition genomics could benefit from unique epigenetic signatures of individuals for the purposes of personalized dietary interventions. An epigenetic information society will face obvious social choices between a policy of laissez-faire versus a policy of intervention and rehabilitation in global health. Some will also undoubtedly argue that the inevitability of natural selection invariably points to not intervening (too much, if at all) in such a transgenerational way (if we can help it) as the genome will adapt to any viable environmental stress through its inherent plasticity, regardless of the resulting social conditions through which it materializes. The article concludes that ultimately, global health will benefit from promoting appropriate governance of the biological informational value of foods together with strong educational programs for the public.

There is an increasing number of genomic research studies occurring in African countries, as well as recently enacted funding mechanisms to build capacity to conduct genomic research in Africa. While there is extensive literature and debate about the various national and international laws and policies related to genomic research in general, most discussions focus on developed and high-income countries. Genomic research, however, is a global endeavor requiring enrollment, data-sharing, and data-storage policies that involve socially, economically, and ethnically diverse populations. On one hand, the translation of genomic medicine into personalized clinical care will fail globally if as many different populations as possible are not adequately represented at the research stage. On the other, future internationally sponsored genomic research projects that could translate into personalized medicine applications will be in jeopardy in communities where genomic researchers neglect to consider local laws, beliefs, and needs. This paper discusses the opportunities and challenges for investigators and research institutions seeking to conduct genomic research in Nigeria. Specifically, we highlight the potential role of Nigerian laws, such as Nigeria’s National Code of Health Research Ethics and the role of local bodies, such as Community Advisory Committees, in promoting genomic research approaches that are appropriate for the local environment. This article thus contributes to a growing body of literature on global bioethics and personalized medicine in resource-limited settings.

Sequencing the human genome, more than a decade ago, initiated the genomics era and the promise of truly personalized medicine. However, much is still unknown about the genetic factors that affect drug efficacy and toxicity, and there are currently very few clinically useful pharmacogenetic tests available. Of these, even fewer are potentially of benefit to developing countries in Africa because pharmacogenetic screening tests are often not applicable to African populations with their unique genetic profiles. Yet, pharmacogenetic tests that accurately predict drug response and toxicity can have a major impact on efficient and effective healthcare in Africa, where the burden of disease is greatest. HIV/AIDS, malaria, and tuberculosis are responsible for approximately 2.5 million deaths in Africa annually, and improving medical care for just these three infectious diseases would save millions of lives. A number of potential biomarkers have been reported that purportedly influence the efficacy and/or toxicity of antiretroviral, antimalarial, and antituberculosis drugs, but more research is required to completely understand the pharmacogenetic applications associated with these treatments. Another 2 million people, however, are dying of preventable and easily curable diseases, such as diarrhoeal and lower respiratory tract diseases. Although pharmacogenetics can play a pivotal role in combating the disease and therapeutic burden in Africa in the future, a multifaceted approach is required to provide effective, affordable and personalized healthcare while also addressing the extreme poverty and other related problems of the people in Africa.

The current drug development framework grants the innovator companies the opportunity to market a new drug exclusively for a defined time period under patent protection. After the patent protection period ends, other companies are permitted to produce their own generic version provided they meet bioequivalance. Accordingly, the test compound and the reference compound pharmacokinetic parameters are expected to be within 80% to 125% in terms of Cmax (maximum plasma concentration) and AUC (area under the curve). Generally, bioequivalence trials are carried out in healthy volunteers as a crossover, open, two-way, randomized design where each volunteer takes both test and reference medication in different periods. The remit of a bioequivalence trial is investigating the similarity of test and reference compounds without observing the pharmacodynamics or therapeutic concentration of the medication. If the trial medication has a bioactive metabolite, in this case, both the main molecule and bioactive metabolite should demonstrate bioequivalancy in terms of pharmacokinetic parameters. Both inter- and intra-individual pharmacokinetic variability can be impacted through pharmacogenetic differences and gene expression regulation at an individual and population level. Surprisingly, pharmacogenetics has been considered very little in bioequivalence studies. This expert review article aims to initiate a discussion on the ways in which these two fields of biomedicine offer synergy for innovation, and the ways forward to address the extant challenges at the unique intersection of pharmacogenetics and bioequivalance research and development.

Biomarkers are defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological or pathogenic processes or pharmacological responses to a therapeutic intervention. Over the past few decades, a growing interest in the identification of biomarkers has emerged in order to detect different pathologies in the early stages. Thus, it would be possible to provide a customized treatment to the patient, improving their outcome. Owing this purpose, proteomics has allowed the development of new methodologies and technologies which are able of detecting low-abundance proteins. This is due, in part, to the development of novel promising materials, such as quantum dots or silicon nanowires. Such emerging approaches come with the advantage of their high sensitivity, low-volume requirements or the potential high-throughput applications, among others. However, since huge information has been generated through nanoproteomic techniques, only few applications have arrived to the clinics. Referring to personalized medicine and targeted therapies, it has to be mentioned that the development of more specific drugs can be improved by the use of biomarkers, helping with decisions about dose, schedule and patient population. In this review, we summarize and highlight the utility of biomarkers identified through nanoproteomics for personalized medicine as well as the applications in the clinic and the future perspectives

Publication of the research outputs is a vital step of the research processes and a gateway between the laboratory and the global society. Open Access is revolutionizing the dissemination of scientific ideas, particularly in the field of public health pharmacogenomics that examines the ways in which pharmacogenomics impacts health systems and services at a societal level, rather than a narrow bench to bedside model of translation science. This manuscript argues that despite some limitations and drawbacks, open access has profound ethical, political and societal implications especially on underdeveloped and developing countries, and that it provides opportunities for science to grow in these resource-limited countries, particularly in the era of a severe economic and financial crisis that is imposing cuts and restrictions to research.

The involvement of neurotrophic factors, notably brain-derived neurotrophic factor (BDNF) has been suggested in the pathogenesis of major depressive disorder (MDD) and in the response of antidepressant treatment both in preclinical and clinical studies. Thus, genetic variation in human BDNF gene may be associated with MDD susceptibility and be related to treatment response to antidepressants in patients with MDD. Two hundred and eighty-eight Taiwanese patients diagnosed with MDD and 397 participants with similar mean age and gender distribution were enrolled in the study, and three markers, including rs6265 (Val66Met) in the BDNF gene were examined for their association with MDD and 4-week response to selective serotonin reuptake inhibitors (SSRI) (n = 216) using single- and haplotype-based analyses. The results showed that the Met allele of rs6265 was in allelic association with MDD. Haplotype analysis of marker combination rs2049046-rs7103411-rs6265 further indicated the association between BDNF genetic polymorphisms and MDD (global permutation p = 0.0007). Regarding 4-week SSRI treatment response and controlling the effect of relevant covariates using logistic regression, the heterozygotes of rs7103411 and rs6265 had higher treatment responder percentage than their homozygous analogs. Furthermore, MDD patients carrying AGA-TAG diplotype tended to be the responders to 4-week SSRIs treatment compared with the non-AGA-TAG diplotype carriers (corrected p= 0.048). One strength of our study is the relatively large sample size. Our findings suggest that BDNF may be a susceptibility gene for MDD, and may also confer a heterosis effect for antidepressant treatment response.