Recent Patents on Biotechnology - Volume 8, Issue 2, 2014

The special issue “Current topics in Pharmacogenomics”, will be wonderful reference for new generation pharmacists & future pharmacists to understand the current status of Pharmacogenomics (Future medicine or personalized medicine) and its future prospects. “No two individuals are alike” and diversities among the individuals can potentially contribute their reaction (positive or negative) to the drug. The main focus of Human Genome Project is developing personalized medicine based on the genome content of the individual to maximize the drug efficacy and minimize the un-wanted side effects. Disciplines such as Biotechnology, Bioinformatics, Genomics, Genetic Engineering, Molecular Biology, Pharmaceuticals Sciences, Clinical Practice, and Mathematics are the core of Pharmacogenomics. The main focus of this issue is to bring novel research topics, development of new pharmacogenomics tools in personalized medicine for major diseases and few patents in these areas. From a therapeutic approach, the future of pharmacy and pharmacogenomics will be a major guiding tool for drug therapy which will move the clinical practice away from “one size fits all” approach. Few topics have also been included to cover the research developing novel diagnostics, biomarkers and preventive solutions using one or more of the core areas of Pharmacogenomics. The first review article in this special issue contributed by Dr. Andrew Borkowski et al. discusses on the implications of polymorphisms in warfarin dosing, pharmacogenomics tests available for warfarin dosing along with the clinical model for the implementation of pharmacogenomics test results and complexities associated with these patented methodologies. Second review contributed by Dr. John Allen et al. discusses the potential use of pharmacogenomic approaches in the critically ill for the management of acute coronary syndrome (ACS), invasive fungal infection, and pain management along with some recent patents associated with it and the current barriers for Pharmacogenomics-guided therapy in the critically ill. Third review contributed by Dr. Kalyan Chapalamadugu et al. discusses various pharmacogenomics approaches for cardiovascular complications in patients with metabolic disorders such as diabetes and obesity. Fourth review contributed by Dr. Ashim Malhotra et al. highlights for the first time on the possible sources of pharmacogenomics variations that may affect the treatment of the pediatric cardiomyopathy called Barth syndrome (BTHS). In this article authors also shed light on the possible treatment options along with the future directions. Fifth article contributed by Dr. Charles Preuss et al. elucidates upon the potential role of nutraceuticals (natural products) as dietary supplements to prevent or diminish the disease risk in the population carrying certain polymorphisms that can increase the susceptibility to certain diseases. Sixth article contributed by Dr. Thea Moore et al. focuses on the current impression of pharmacogenomics in reducing the life-threatening adverse effects of psychotropics in patients with psychiatric and neurological disorders with special emphasis on atypical antipsychotics due to their wide usage. Finally, the seventh article contributed by Dr. Manju Pathak discusses the role of functional foods in disease management for patients with Type 2 Diabetes Mellitus. We are grateful to all contributors of this special issue and to all our reviewers for their excellent feedback, which made this issue a wonderful guide for the future pharmacists and pharmacogenomics specialists. I wish this special issue will give more encouragement for the scientific community to bring more special issues, topics and books that can promote complete implementation of pharmacogenomics in clinical settings.

Warfarin pharmacogenomic testing has become a prime example of the utility of personalized molecular testing in the modern clinical laboratory. Warfarin is a commonly used drug for the prevention and treatment of thromboembolic complications in a variety of clinical situations. However, a number of factors lead to a high interindividual variability in dose requirements. Among the primary factors in this variability are genetic polymorphisms in general patient populations, which can account for 35-50% of varying dose requirements among patients. In this review, we discuss the implications of polymorphisms in the cytochrome P-450 enzyme 2C9 (CYP2C9) and Vitamin K Epoxide Reductase Enzyme Complex subunit 1 (VKORC1) as they relate to therapeutic warfarin dosing. We discuss the clinical utility of pharmacogenomics testing as related to warfarin dosing, and propose a clinical model for the implementation of the pharmacogenomic test results. Finally, we provide a brief overview of the currently available commercial testing platforms with discussion of the complexities of utilizing patented methodologies in bringing genetic testing such as this to the clinical laboratory.

Critically ill patients often are at high-risk for adverse drug reactions (ADRs), mainly due to alterations in pharmacokinetic and pharmacodynamic (PK/PD) parameters. These PK/PD differences in can also lead to inadequate therapeutic response to many commonly used drugs in this patient population. Frequently in the critically ill patient, medications are utilized based on a “trial-and-error” approach. Furthermore, drug dosing in the critically ill largely remains a “one-size-fits-all” phenomenon, utilizing dosing based on PK studies in healthy volunteers. Known differences in gene variation among the general population can greatly alter response to drug therapy. The use of pharmacogenomics (PGX) to aid in the development of individualized pharmacotherapeutic regimens, potentially may reduce ADRs and increase therapeutic efficacy. Potential uses of PGX include: identification of patients who are particularly susceptible to ADRs; and patients whom are more likely to benefit from a particular drug therapy, based on the patient’s own genetic profile. This review will focus on potential applications of PGX in the critically ill, including management of acute coronary syndromes (ACS), invasive fungal infections, and pain management. Current barriers to PGX-guided therapy in the critically ill and recent patent developments in the clinical application of PGX will also be discussed.

Heart disease is a major cause of death in US and worldwide. The complex interplay of the mechanisms between diabetes, obesity and inflammation raises concerns for therapeutic understanding and developing treatment options for patients. Recent advances utilizing pharmacogenomics has helped researchers to probe in to disease pathophysiology and physicians to detect and, diagnose the disease in patients. The understanding developed in the area primarily addresses the issue focusing on the nature and asks the question ‘Why’ some individuals respond to the standard medication regimen and others do not. The central idea that genomics play a vital part in how the healthcare providers: physician, pharmacist, and nurse provide treatment utilizing the best practices available for maximum benefits. Pharmacogenomics is the scientific basis which offers the fundamental understanding for diseases, based on which therapeutic approaches can be designed and delivered. The discovery that not all humans respond to the drug in the same way is a ‘paradigm shift’ in how current therapies are offered. The area of pharmacogenomics at its core is linked to the genetic basis for the disease and the response to treatment. Given that diabetes and obesity are major metabolic ailments globally wherein patients also often suffer from cardiac disorders, a comprehensive genetic and pharmacogenomic understanding of these conditions enable the development of effective therapeutic strategies. In this review, we discuss various pharmacogenomic approaches with special emphasis on heart disease as it relates to diabetes and obesity. Recent information in regard to relevant patents in this topic are also discussed.

Barth syndrome (BTHS) is a genetic, X-linked, rare but often fatal, pediatric skeletal- and cardiomyopathy occurring due to mutations in the tafazzin gene (TAZ). TAZ encodes a transacylase involved in phospholipid biosynthesis, also called tafazzin, which is responsible for remodeling the inner mitochondrial membrane phospholipid, cardiolipin (CL). Tafazzin mutations lead to compositional alterations in CL molecular species, causing extensive mitochondrial aberrations and ultrastructural muscle damage. There are no specific treatments or cure for BTHS. Current therapy is largely palliative and aimed at treatment of organ-specific complications during disease progression. Polypharmacy frequently occurs during treatment and may lead to severe adverse events. Adverse reactions may originate from exogenous factors such as the inadvertent co-administration of contraindicated drugs. Theoretically, endogenous factors such as polymorphic variations in genes encoding drug metabolizing enzymes may also precipitate fatal toxicity. Investigation of the consequences of pharmacogenomic variations on BTHS therapy is lacking. To our knowledge, this review presents the first examination of the possible sources of pharmacogenomic variations that may affect BTHS therapy. We also explore BTHSspecific patents for possible treatment options. The patents discussed suggest innovative strategies for treatment, including feeding linoleic acid to patients to overcome compositional CL deficiency; or the use of 2S,4R ketoconazole formulations to augment CL levels; or the delivery of mitochondrial stabilizing cargo. Future research directions are also discussed.

The post genomic era has promised major breakthroughs in personalized medicine which will improve a patient’s health by selecting treatments including diet based on the patient’s unique DNA sequence. The post genomic era is allowing scientists and clinicians to examine an individuals’ DNA and then recommend the best diet in order to remain healthy and attenuate disease processes which the individual might be predisposed to because of their genetic make-up, e.g., cardiovascular disease. Nutrigenomics and nutrigenetics are related terms to pharmacogenomics and pharmacogenetics with an emphasis on diet or nutrition. There has been an increasing interest in consumers on natural medicines or Nutraceuticals in order to remain healthy. The post genomic era will allow a patient to visit their physician who will screen the patients DNA on a silicon chip. This will indicate which of the patient’s genes have polymorphisms, e.g., a single nucleotide polymorphism (SNP) that might lead the patient to be more susceptible to certain diseases and then the physician could prescribe the appropriate dietary supplements to prevent or diminish these potential diseases. Several recently published patents are discussed in the article covering recent developments in the field.

Psychotropic medications are used for numerous psychiatric and neurologic disorders, and are associated with in some cases life-threatening adverse effects, high acquisition costs, stringent monitoring requirements, and potential interactions with other medications. Because of the risks of adverse effects and need for adherence, risk mitigation strategies are being implemented to protect consumers. An understanding of receptor activities, cytochrome P450 2D6 and 2C19 metabolism, overlapping pharmacology, and polymorphic biomarkers for the dopamine 2 D2 receptor gene (DRD2) and dopamine 3 D3 receptor gene (DRD3), serotonin 2A and 2C receptor genes (5HTR2A and 5HTR2C), and human leukocyte antigen (HLA) variants creates opportunities for the integration of pharmacogenomics, and can assist in the application of personalized medicine in this arena. In this review, we discuss the current impression of pharmacogenomic principles pertaining to select psychotropics, with attention given to the atypical antipsychotics, due to their wide use across a broad spectrum of psychiatric disorders (e.g. bipolar disorder, depression, schizophrenia). Patents involving aripiprazole, clozapine, olanzapine, and risperidone will be discussed.

Diabetes is the common, exponentially growing, serious human health problem existing globally. Risk factors like genetic predisposition, lack of balanced diet, inappropriate and lethargic lifestyle, overweight, obesity, stress including emotional and oxidative and lack of probiotics in gut are found to be the causing factors either in isolation or in synergy predisposing Diabetes. High blood sugar is a common symptom in all types of diabetes mellitus and the physiological cause of diabetes is lack of hormone Insulin or resistance in function faced by insulin. Low levels of Insulin causes decreased utilization of glucose by body cells, increased mobilization of fats from fat storage cells and depletion of proteins in the tissues of the body, keeping the body in crisis. The functional foods help achieving optimal physiological metabolism and cellular functions helping the body to come out of these crises. The mechanism of the functional foods is envisaged to act via optimizing vitamins, minerals, essential amino acids, prebiotics and probiotics. This paper reviews role of functional foods of plant origin in the regulation of blood sugar in type 2 diabetes mellitus and also discusses some vital patents in this area. The article aims at creating awareness about key food ingredients in order to prevent most acute effects of diabetes mellitus and to greatly delay the chronic effects as well.

The industrial production of recombinant proteins preferentially requires the generation of stable cell lines expressing proteins in a quick, relatively facile, and a reproducible manner. Different methods are used to insert exogenous DNA into the host cell, and choosing the appropriate producing cell is of paramount importance for the efficient production and quality of the recombinant protein. This review addresses the advances in recombinant protein production in mammalian cell lines, according to key patents from the last 30 years.

Since the time of Hippocrates, physicians have known that the odour of human breath can provide clues to diagnosis. In the past, hydrogen peroxide which is a marker of inflammatory diseases and oxidative stress was the most studied substance in the exhaled breath which was detectable in the liquid that obtained by condensing or cooling. The advantages of breath analysis are that it is convenient, non-invasive, and could be performed with children as well as mechanically ventilated patients. Today, exhaled nitric oxide has been studied extensively, especially in relation to asthma. More than a thousand different volatile organic compounds have been observed in low concentrations in normal human breath. Alkanes and methylalkanes have been increasingly used by physicians as a novel method to diagnose many diseases without discomforts of invasive procedures. Although the limitations of measurement of exhaled nitric oxide in direct diagnosis of infectious pulmonary TB, it may have potential development as a cost-effective replacement of chest radiological examination in screening algorithms. None of the individual exhaled volatile organic compound alone is specific for disease. Exhaled breath analysis techniques may be available to diagnose and monitor the diseases in home setting when their sensitivity and specificity are expected to improve in the future. Here, we also discussed some patents related to the topic.