Recent Patents on Biotechnology (v.8, #2)
Editorial (Thematic Issue: Current Topics in Pharmacogenomics) by Siva Kumar Panguluri, Kevin B. Sneed, Yashwant Pathak, Shufeng Zhou (109-109).
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 itsfuture prospects.“No two individuals are alike” and diversities among the individuals can potentially contribute their reaction (positive ornegative) to the drug. The main focus of Human Genome Project is developing personalized medicine based on the genomecontent 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, andMathematics are the core of Pharmacogenomics. The main focus of this issue is to bring novel research topics, development ofnew pharmacogenomics tools in personalized medicine for major diseases and few patents in these areas. From a therapeuticapproach, the future of pharmacy and pharmacogenomics will be a major guiding tool for drug therapy which will move theclinical practice away from “one size fits all” approach. Few topics have also been included to cover the research developingnovel 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 ofpolymorphisms in warfarin dosing, pharmacogenomics tests available for warfarin dosing along with the clinical model for theimplementation 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 criticallyill for the management of acute coronary syndrome (ACS), invasive fungal infection, and pain management along withsome 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 cardiovascularcomplications 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 pharmacogenomicsvariations that may affect the treatment of the pediatric cardiomyopathy called Barth syndrome (BTHS). In this articleauthors 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) asdietary supplements to prevent or diminish the disease risk in the population carrying certain polymorphisms that can increasethe susceptibility to certain diseases.Sixth article contributed by Dr. Thea Moore et al. focuses on the current impression of pharmacogenomics in reducing thelife-threatening adverse effects of psychotropics in patients with psychiatric and neurological disorders with special emphasison atypical antipsychotics due to their wide usage.Finally, the seventh article contributed by Dr. Manju Pathak discusses the role of functional foods in disease managementfor 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 thisissue a wonderful guide for the future pharmacists and pharmacogenomics specialists. I wish this special issue will give moreencouragement for the scientific community to bring more special issues, topics and books that can promote complete implementationof pharmacogenomics in clinical settings.
Warfarin Pharmacogenomics: Recommendations With Available Patented Clinical Technologies by Andrew A. Borkowski, Avni Kardani, Stephen M. Mastorides, L.Brannon Thomas (110-115).
Warfarin pharmacogenomic testing has become a prime example of the utility of personalized molecular testingin the modern clinical laboratory. Warfarin is a commonly used drug for the prevention and treatment of thromboemboliccomplications in a variety of clinical situations. However, a number of factors lead to a high interindividual variability indose 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 implicationsof polymorphisms in the cytochrome P-450 enzyme 2C9 (CYP2C9) and Vitamin K Epoxide Reductase EnzymeComplex subunit 1 (VKORC1) as they relate to therapeutic warfarin dosing. We discuss the clinical utility of pharmacogenomicstesting as related to warfarin dosing, and propose a clinical model for the implementation of the pharmacogenomictest results. Finally, we provide a brief overview of the currently available commercial testing platforms with discussionof the complexities of utilizing patented methodologies in bringing genetic testing such as this to the clinical laboratory.
Pharmacogenomics in the Intensive Care Unit: Focus on Potential Implications for Clinical Practice by John M. Allen, Shyam Gelot (116-122).
Critically ill patients often are at high-risk for adverse drug reactions (ADRs), mainly due to alterations inpharmacokinetic and pharmacodynamic (PK/PD) parameters. These PK/PD differences in can also lead to inadequatetherapeutic 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 remainsa “one-size-fits-all” phenomenon, utilizing dosing based on PK studies in healthy volunteers. Known differences ingene 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 increasetherapeutic efficacy. Potential uses of PGX include: identification of patients who are particularly susceptible toADRs; and patients whom are more likely to benefit from a particular drug therapy, based on the patient's own geneticprofile. This review will focus on potential applications of PGX in the critically ill, including management of acute coronarysyndromes (ACS), invasive fungal infections, and pain management. Current barriers to PGX-guided therapy in thecritically ill and recent patent developments in the clinical application of PGX will also be discussed.
Pharmacogenomics of Cardiovascular Complications in Diabetes and Obesity by Kalyan Chapalamadugu, Siva K. Panguluri, Aimon Miranda, Kevin B. Sneed, Srinivas M. Tipparaju (123-135).
Heart disease is a major cause of death in US and worldwide. The complex interplay of the mechanisms betweendiabetes, obesity and inflammation raises concerns for therapeutic understanding and developing treatment optionsfor patients. Recent advances utilizing pharmacogenomics has helped researchers to probe in to disease pathophysiologyand physicians to detect and, diagnose the disease in patients. The understanding developed in the area primarily addressesthe issue focusing on the nature and asks the question 'Why' some individuals respond to the standard medicationregimen 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 isthe scientific basis which offers the fundamental understanding for diseases, based on which therapeutic approaches canbe designed and delivered. The discovery that not all humans respond to the drug in the same way is a 'paradigm shift' inhow current therapies are offered. The area of pharmacogenomics at its core is linked to the genetic basis for the diseaseand the response to treatment. Given that diabetes and obesity are major metabolic ailments globally wherein patients alsooften suffer from cardiac disorders, a comprehensive genetic and pharmacogenomic understanding of these conditions enablethe development of effective therapeutic strategies. In this review, we discuss various pharmacogenomic approacheswith special emphasis on heart disease as it relates to diabetes and obesity. Recent information in regard to relevant patentsin this topic are also discussed.
Pharmacogenomic Considerations in the Treatment of the Pediatric Cardiomyopathy Called Barth Syndrome by Ashim Malhotra, Parmbir Kahlon, Timothy Donoho, Ian C. Doyle (136-143).
Barth syndrome (BTHS) is a genetic, X-linked, rare but often fatal, pediatric skeletal- and cardiomyopathy occurringdue 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 aberrationsand ultrastructural muscle damage. There are no specific treatments or cure for BTHS. Current therapy is largelypalliative and aimed at treatment of organ-specific complications during disease progression. Polypharmacy frequentlyoccurs during treatment and may lead to severe adverse events. Adverse reactions may originate from exogenous factorssuch as the inadvertent co-administration of contraindicated drugs. Theoretically, endogenous factors such as polymorphicvariations in genes encoding drug metabolizing enzymes may also precipitate fatal toxicity. Investigation of the consequencesof pharmacogenomic variations on BTHS therapy is lacking. To our knowledge, this review presents the first examinationof the possible sources of pharmacogenomic variations that may affect BTHS therapy. We also explore BTHSspecificpatents for possible treatment options. The patents discussed suggest innovative strategies for treatment, includingfeeding linoleic acid to patients to overcome compositional CL deficiency; or the use of 2S,4R ketoconazole formulationsto augment CL levels; or the delivery of mitochondrial stabilizing cargo. Future research directions are also discussed.
Genomics and Natural Products: Role of Bioinformatics and Recent Patents by Charles Preuss, Malay K. Das, Yashwant V. Pathak (144-151).
The post genomic era has promised major breakthroughs in personalized medicine which will improve a patient'shealth by selecting treatments including diet based on the patient's unique DNA sequence. The post genomic era isallowing scientists and clinicians to examine an individuals' DNA and then recommend the best diet in order to remainhealthy 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 pharmacogeneticswith an emphasis on diet or nutrition. There has been an increasing interest in consumers on natural medicines or Nutraceuticalsin order to remain healthy. The post genomic era will allow a patient to visit their physician who will screenthe patients DNA on a silicon chip. This will indicate which of the patient's genes have polymorphisms, e.g., a single nucleotidepolymorphism (SNP) that might lead the patient to be more susceptible to certain diseases and then the physiciancould prescribe the appropriate dietary supplements to prevent or diminish these potential diseases. Several recently publishedpatents are discussed in the article covering recent developments in the field.
Pharmacogenomics in Psychiatry: Implications for Practice by Thea R. Moore, Angela M. Hill, Siva K. Panguluri (152-159).
Psychotropic medications are used for numerous psychiatric and neurologic disorders, and are associated within some cases life-threatening adverse effects, high acquisition costs, stringent monitoring requirements, and potential interactionswith other medications. Because of the risks of adverse effects and need for adherence, risk mitigation strategiesare being implemented to protect consumers. An understanding of receptor activities, cytochrome P450 2D6 and 2C19metabolism, overlapping pharmacology, and polymorphic biomarkers for the dopamine 2 D2 receptor gene (DRD2) anddopamine 3 D3 receptor gene (DRD3), serotonin 2A and 2C receptor genes (5HTR2A and 5HTR2C), and human leukocyteantigen (HLA) variants creates opportunities for the integration of pharmacogenomics, and can assist in the applicationof personalized medicine in this arena. In this review, we discuss the current impression of pharmacogenomic principlespertaining to select psychotropics, with attention given to the atypical antipsychotics, due to their wide use across abroad spectrum of psychiatric disorders (e.g. bipolar disorder, depression, schizophrenia). Patents involving aripiprazole,clozapine, olanzapine, and risperidone will be discussed.
Diabetes Mellitus Type 2 and Functional Foods of Plant Origin by Manju Pathak (160-164).
Diabetes is the common, exponentially growing, serious human health problem existing globally. Risk factorslike genetic predisposition, lack of balanced diet, inappropriate and lethargic lifestyle, overweight, obesity, stress includingemotional and oxidative and lack of probiotics in gut are found to be the causing factors either in isolation or in synergypredisposing Diabetes. High blood sugar is a common symptom in all types of diabetes mellitus and the physiologicalcause of diabetes is lack of hormone Insulin or resistance in function faced by insulin. Low levels of Insulin causes decreasedutilization of glucose by body cells, increased mobilization of fats from fat storage cells and depletion of proteinsin the tissues of the body, keeping the body in crisis. The functional foods help achieving optimal physiological metabolismand cellular functions helping the body to come out of these crises. The mechanism of the functional foods is envisagedto act via optimizing vitamins, minerals, essential amino acids, prebiotics and probiotics. This paper reviews role offunctional foods of plant origin in the regulation of blood sugar in type 2 diabetes mellitus and also discusses some vitalpatents in this area. The article aims at creating awareness about key food ingredients in order to prevent most acute effectsof diabetes mellitus and to greatly delay the chronic effects as well.
Patents in Therapeutic Recombinant Protein Production Using Mammalian Cells by Virginia Picanco-Castro, Marcela Cristina Correa de Freitas, Aline de Sousa Bomfim, Elisa Maria de Sousa Russo (165-171).
The industrial production of recombinant proteins preferentially requires the generation of stable cell lines expressingproteins in a quick, relatively facile, and a reproducible manner. Different methods are used to insert exogenousDNA into the host cell, and choosing the appropriate producing cell is of paramount importance for the efficient productionand quality of the recombinant protein. This review addresses the advances in recombinant protein production inmammalian cell lines, according to key patents from the last 30 years.
Breath Tests in Diagnosis of Pulmonary Tuberculosis by Attapon Cheepsattayakorn, Ruangrong Cheepsattayakorn (172-175).
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 moststudied substance in the exhaled breath which was detectable in the liquid that obtained by condensing or cooling. Theadvantages of breath analysis are that it is convenient, non-invasive, and could be performed with children as well as mechanicallyventilated 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 humanbreath. Alkanes and methylalkanes have been increasingly used by physicians as a novel method to diagnose many diseaseswithout discomforts of invasive procedures. Although the limitations of measurement of exhaled nitric oxide in directdiagnosis of infectious pulmonary TB, it may have potential development as a cost-effective replacement of chest radiologicalexamination in screening algorithms. None of the individual exhaled volatile organic compound alone is specificfor disease. Exhaled breath analysis techniques may be available to diagnose and monitor the diseases in home settingwhen their sensitivity and specificity are expected to improve in the future. Here, we also discussed some patents relatedto the topic.
Patent Selections (176-177).