June 2007
Pharmacogenomics
A true story of personalized medicine
What is pharmacogenomics?
Pharmacogenomics is the study of how an individual's genetic inheritance affects the body's response to drugs. The term comes from the words pharmacology and
genomics and is thus the intersection of pharmaceuticals and genetics.
Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each person's own genetic makeup. Environment, diet, age, lifestyle, and state of health all can influence a person's response to medicines, but understanding an individual's genetic makeup is thought to be the key to creating personalized drugs with greater efficacy and safety.
Pharmacogenomics combines traditional pharmaceutical sciences such as biochemistry with annotated knowledge of genes, proteins, and single nucleotide polymorphisms.
Personalized medicine
Personalized medicine is the use of detailed information about a patient's genotype or level of gene expression and a patient's clinical data in order to select a medication, therapy or preventative measure that is particularly suited to that patient at the time of administration. The benefits of this approach are in its accuracy, efficacy, safety and speed. The term emerged in the late 1990s with progress in the Human Genome Project. Research findings over the past decade, or so, in biomedical research have unfolded a series of new, predictive sciences that share the appendage -omics (genomics, proteomics, metabolomics, cytomics). These are opening the possibility of a new approach to drug development as well as unleashing the potential of significantly more effective diagnosis, therapeutics, and patient care.
Author: Amit Katiyar.
SNPs, Pharmacogenetics and
Pharmacogenomics
Single nucleotide substitutions are the most abundant form of polymorphism in the human genome. A number of strategies are being applied to identify SNPs from the human genome; and most of these rely on gel-based sequencing for either direct discovery of SNPs or confirmation of SNPs from indirect methods. SNP maps are used in pharmacogenomics for personalizing medicine and the two common approaches for the use of SNPs in pharmacogenomics include candidate gene approach and Linkage disequilibrium mapping. SNPs are also used to identify patients at greater risk of an
AE, or those patients with a greater
chance of responding to a medicine (pharmacogenetics). However, the use of SNPs as a tool in pharmacogenomics has its own limitations.
Keywords: Single Nucleotide polymorphisms (SNPs), Pharmacogenomics, pharmacogenetics, candidate gene approach, linkage disequilibrium mapping.
SNPs
SNPs are defined as single base-pair positions in genomic DNA that vary among individuals in one or several populations. SNPs represent as much as 90% of all human genetic variation (Kruglyak L, 1999). The least common base alternative must occur in the population at a frequency of atleast 1% for the variant to be considered an SNP (Marth G T et al, 1999). SNPs are believed to underlie susceptibility to such common diseases as cancer, diabetes, cardiovascular, and inflammatory diseases and to contribute to the traits that make individuals unique. SNPs also help to explain why different people respond differently to same drug.
Author: V.S. Mahendran, M. Prasanna Rajesh Kumar
Role of Pharmacogenetics in
determining the variability
in human drug response
A Pharmacogenetic and Pharmacogenomic approach in Asthma Treatment
Over the last decade there has been an increasing appreciation that asthma represents more of a syndrome than a single disease entity. Although phenotypically; most patients manifest the specific features of inflammation, reversible airflow obstruction, and airway hyper responsiveness, there is considerable heterogenecity among other aspects. Thus the type and extent of inflammatory response, the response to environment triggers, and the degree of atopy may all show considerable heterogeneity. perhaps most impressively the data from many clinical traits consistently indicate that the variation in treatment among individuals substaniatially exceed the variation in response within a given individual. Presumably these differences reflect the genetic variability between individuals; variability expressed, for example in differences in drug metabolic rates, drug receptor polymorphisms and even in adverse events. The premise that Pharmacogenetics and pharmacogenomics will provide the ability to use genetic information to determine who will respond favorably or unfavorably to a specific therapeutic initiative.
Explanation of Pharmacogenetics and Pharmacogenomics
Jeffrey
M. Drazen, MD, professor of medicine at Harvard Medical School in Boston, Massachusetts, introduced the topic, emphasizing that a substantial component of the variability of response to a specific asthma treatment is genetic. Pharmacogenetic mechanisms with implications for asthma treatment include:
1) Genetic variations associated with altered uptake, distribution, or metabolism of the specific drug administered.
2) Genetic variants resulting in an unintended action of a drug beyond its therapeutic indication;
3) Genetic variation in the drug target, including genetic variants in the structure of the drug target leading to altered efficacy; and
4) Genetic variants leading to differences in the expression of a physiologic phenotype such that a given target may not be disease- associated in a given patient.
There are 2 important examples of the latter classes of pathogenic mechanisms (i.e. variation in the drug target) in patients with asthma. One example involves the known variation in the coding region of the beta2-adrenergic receptor and is associated with differential responses of the receptor in-vitro as well as different clinical responses in patients. The major point is that the majority of patients with asthma have functional beta2-adregenic receptors, but the nature of the response to treatment via this receptor varies from patient to patient. A second example in asthmatic patients reflects the polymorphic forms of the core promoter of the ALOX5 gene. These polymorphisms have been associated with decreased promoter activity in-vitro and such patients have failed to respond to treatment with an inhibitor of ALOX5.
Authors: V. Sai Mahathi.
Gene Chip: A Fine Molecular
Gene Expression Technology
for Modern Biotech Industry
Biotechnology in recent year has created unprecedented opportunities not only for the manipulation of biological system for humankind and industrial development but also understanding basic life process, consequently, it has become the world fastest growing and most rapidly changing technology. Genetic Engineering is one of the most rapidly growing areas of biotechnological research. Biotechnological research evolves and advances not only through the combination of knowledge but also enhancement and development of new technology using traditional methods to assay gene expression. A new concept of biotechnology comes into play calls as Gene Chip technology or DNA microarray technology or Array technology. Microarray or Gene chip or DNA chip allows researchers as well as scientists to analyze expression of many genes in a single experiment very quickly and result oriented way. Using Gene chip or microarray technology scientists try to understand fundamental aspect of growth and development as well as to explore the underlying genetic causes of many human and plant diseases.
As everybody knows that every cell (plants and animals) contain a full set of chromosomes and identical genes. Gene expression is the term used to describe the transcription of information contained within the DNA. The proper and right expression of a large number of genes is natural phenomenon of normal growth and development and the maintenance of proper health of plants and animals. And due to different conditions disruption or changes in gene expression are responsible for diseases in human and plant.
It is widely believed that thousands of genes and their products (RNAs, and Proteins) in a given organism function in a complicated way that create mystery of life, however traditional methods in molecular biology generally work on a one gene in one experiment basis which was very limited and the whole picture of gene function is hard to obtain.
Authors :Sudhir Sharma,Priyamvada
Turmeric: A Hidden Drug
Class : Liliopsida
Subclass : Commelinids
Order : Zingiberales
Family : Zingiberaceae
Genus : Curcuma
Species : Curcuma longa
Turmeric (Curcuma longa) an indigenous herbal medicine belongs to the zingibaraceae family which is a part of ginger family of herbs. Turmeric (Latin terra merita, “ meritorious earth”), comes from the root of the Curcuma longa plant and has a tough brown skin and a deep orange flesh, is having a sharp, earthy, bitter, peppery flavor. It grows to a height of 5 feet in tropical parts of southern Asia. Sangli, a town in the southern part of the Indian state of Maharashtra, is the largest and most important trading centre for turmeric in Asia or perhaps in the entire world.
Turmeric has been used since ages as domestic food spice, healing remedy and textile dye. In both the Chinese and Indian systems of medicine, turmeric has long been used as a powerful anti-inflammatory agent to treat a wide variety of conditions, including jaundice, menstrual difficulties, bloody urine, hemorrhage, toothache, bruises, chest pain, flatulence and colic.
Nutrients: Turmeric contains protein, fat, minerals, carbohydrates and moisture.
Chemical composition: The essential oil obtained by steam distillation of rhizomeshas has a-phellandrene,sabinene,cineol, borneol ,zingiberene and sesquiterpines. Curcumin (diferuloylmethane) (34%) is responsible for the yellow colour, and comprises curcumin I (94%), curcumin II (6%) and curcumin III (0.3%).
Pharmacological Agent: Curcumin is thought to be the primary pharmacological agent in turmeric. In numerous studies, curcumin's anti-inflammatory effects have been shown to be comparable to the potent drugs hydrocortisone and phenylbutazone as well as over-the-counter anti-inflammatory agents such as Motrin. Unlike the drugs, which are associated with significant toxic effects (ulcer formation, decreased white blood cell count, intestinal bleeding), curcumin produces no toxicity.
“A Hypothesis to Integrate the Therapeutic Benefits of
Gene Therapy and Hypoxia-Reversal Radiotherapy for Cancer via
A Novel Non-Covalent Oxygen-DNA Complex”
Abstract
Several genes, most commonly being the Tumor Suppressor p53, are being extensively investigated as Gene Therapy candidates to treat cancers1. Solid tumors are difficult to treat with conventional Radiotherapy, due to their hypoxic, low oxygen, environment2. Extensive theoretical study and preliminary spectrophotometric experiments were carried out to see whether a novel, non-covalent “Oxy-DNA” molecule can be created, with an aim to combine the above 2 therapies in a single complex. Both, native B-form and partially heat-denatured form of DNA were oxygenated. We have proposed a hypothesis to explain the results obtained, and on that basis, have further proposed some model procedures for synthesis of a stable oxygen-DNA complex, with minimum damage to DNA biochemistry. The reaction is theoretically shown to be reversible when oxygen is removed3. This work throws open the possibility of combining two of the most vital molecules of life, in a single complex.
Keywords: Oxygen-DNA, Non-covalent Interaction, Partial Melting, UV-spectrophotometry.
Introduction and Theoretical Study
In the past years, it has been well established that proto-oncogenes are responsible for the initiation and development of most cancers. Gene-based therapies for cancer in clinical trials include strategies that involve augmentation of immunotherapeutic and chemotherapeutic approaches. These strategies include ex-vivo and in-vivo cytokine gene transfer, drug sensitization with genes for prodrug delivery, and the use of drug-resistance genes for bone marrow protection from high-dose chemotherapy. Inactivation of oncogene expression and gene replacement for tumor suppressor genes are among the strategies for targeting the underlying genetic lesions in the cancer cell. One of the future areas of research in this field includes identifying synergies between gene-based agents and other cancer therapeutics4. Such a possible synergy is what we have intended to investigate.
Authors:Rupak Doshi, Viju Thomas Varghese.