Biotechnology and Bioinformatics: More Drug Targets

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Table of Contents

More drug Targets
Research groups/Companies
Major problems
Real benefits
References

More drug Targets

Drug targets are molecular structures or proteins that pharmaceutical industries are designing drugs to help in preventing or curing diseases. The proteins, pathogenic microorganisms, have distinct purposes in the human body. Since proteins are in different groups due to duplication of the gene, the drug targets are also in different families. The families include the kinases, phosphates, nuclear receptors, and GPCRs (Imming, Sinning, & Meyer 2006). These targets, through clinical effects, specifically interact with the drugs in diagnosing the disease. From this definition approach, there are some constrictions, such as the absence of technique in monitoring the dynamic interaction of proteins and drugs yet diseases, just as life is constantly changing at different instances. This factor has confined the human population to deal with targets as stationary bodies. Secondly, the purpose of medicine omits the tools of pharmacology.

Presently, there are averages of 500 therapeutic targets or nucleic acids and proteins that drugs are targeting, but of late, it has moved to 324 are for FDA-approved clinical drugs (Chen, Ji & Chen 2002). In drug design, the human genome helps in finding the genes that have a direct link with different diseases. These genetic components may be due to inheritance or body response to environmental changes thus altering the genomes. Before drug design, researchers must carry out an in-depth analysis of a specific target protein to validate its role. According to Chen, Ji & Chen (2002), the process helps in understanding the disease molecular mechanisms more clearly; consequently, leading to the development of better preventive tests, treatment, and cures. In addition, the process of identifying and validating new drug targets is of immense importance in drug discovery in the pharmaceutical line. Early prediction of the potential applications of proteins as a drug target can effectively fasten the process of drug discovery that targets the protein. The new designs of drugs are less toxic and more potent.

Researchers cannot only discover more drug targets with the use of modern computer technology and a better understanding of various disease mechanisms but also discover specific drugs that can interact with both the symptoms and causes of the disease. The mass data analysis in bioinformatics helps unearth the wealth of information that can create a clear understanding of the fundamental biological organisms. Pharmacologists should come up with more drug targets as this will enable the production of a specific drug for a specific disease.

Currently, many medicines have more side effects, coupled with a lot of disease resistance to drugs. For instance, tuberculosis (TB) remains a key cause of infectious morbidity and mortality treatment, in spite of the presence of the BCG vaccine and chemotherapy. The mycobacterium TB pathogen causes nearly nine million disease fresh infection cases and about 1.5 – 2 million deaths yearly (Ying 2012, p. 719). With drug-resistant TB, such as multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) on the rise, extensive research is underway to come up with exactly more drug targets that will help in controlling the disease. The TB case is immensely under threat by HIV infection and XDR/MDR-TB; they lower the immune system thus easily increasing the susceptibility of contracting TB. However, with more drug targets, these cases will stop existing hence creating a profound impact on varied fields like biotechnology, agriculture, and energy. Furthermore, the long TB therapy period will cease to exist, as immense research activities will reveal more details on the persister bacteria found in the tubercle bacillus; therefore, drugs development that targets the persisted bacilli can come up.

Another example was the research on a new drug target for treating heart complications. Researchers at Mount Sinai School of Medicine discovered a small ubiquitin-like modifier that was notably decreasing in those with heart failures (Promising new drug target discovered for treatment and prevention of heart failure 2012, August 25). The researchers noted an improvement in cardiac function upon injection of the protein that regulates the operation of transporter genes into the patient’s hearts through gene therapy.

Research groups/Companies

Jeffrey Conn Research Group

This is a research group that has its base in Nashville, Tennessee. Their fundamental objective is developing a vivid understanding of signals in the central nervous system. Precisely, they study the involvement of the molecular and cellular mechanisms in controlling the chemical and electrical signals in the brain (Jeffrey Conn Research Group n.d). Moreover, the groups’ interest lies in bringing forth how signals vary in certain neuronal circuits; the group is researching drug targets to help in reducing human disorders under neurology and psychiatry. Further, Jeffrey Conn Research Group uses cheminformatics and high throughput screening (HTS) dealing in small molecule reagents, which help in certifying therapeutic approaches and comprehending the biology of signals in the central nervous system. Presently, they are carrying out research on a novel treatment for Parkinson’s disease, drug addiction, Alzheimer’s disease, schizophrenia, and severe anxiety disorders. Under neuromodulation, most of their attention is on the family of G protein-coupled glutamate receptors known as metabotropic glutamate receptors (mGluRs). Jeffrey Conn Research Group (n.d) puts it that the study looks into the role of mGluRs in controlling transmission through basal ganglia circuits, which regulates the motor function and processing of information flow to the cortex. Jeffrey Conn Research Group is looking forward to identifying novel ligands for the specific target in order to help in understanding the functions of proteins in the neuronal circuit. The group has made tremendous steps towards discovering drugs that could lead to the prevention and treatment of the above diseases and other central nervous system disorders.

Metabolic Solutions Development Company (MSDC)

MSDC is a company that investigates novel molecular targets with an aim of developing new therapeutics for treating, such as type 2 diabetes and insulin resistance. This drug discovery company; therefore, aims at treating age-related mitochondrial dysfunction under the metabolic diseases (Metabolic Solutions n.d). In order to treat diabetes, there is urgent need to find insulin sensitizers, which are safe thus treating metabolic dysfunction and minimally affecting the off-target effects. MSDC scientists have discovered a new protein complex: mTOT. This mitochondrial complex has made the scientist develop new insulin sensitizers that have the capability of producing durable anti-diabetic effects. At the same time, MSDC developed two insulin sensitizers, MSDC-0602 and MSDC-0160 (Metabolic Solutions n.d). At the clinical trials stage, the interaction between the two insulin sensitizers and mTOT complex have been able to lower glucose levels without adverse side effects. The company’s research team, after the findings, has been able to understand this pharmacological aspect hence allowing for development of novel therapeutic agents. The new therapeutic agents help in treatment of patients with type 2 diabetes.

SignaBlok

This company specializes on four therapeutic areas: atherosclerosis, cancer, inflammatory and immune diseases (Drug Discovery Research – Signablok n.d), in which they use a new model of cell signaling: the SCHOOL (Signaling Chain HOmoOLigomerization). The model uncovered a signaling mechanism through membrane receptors. Additionally, the model opened room for development of new drugs, which helped in controlling numerous serious diseases. This disrupts functional coupling between recognition and signaling, receptor machineries, to modulate cell response (Drug Discovery Research – Signablok n.d). The SCHOOL peptide therapeutics opened avenues for membrane-receptor modulation. Besides, the research company is developing integrated nanosystems, which will help to design drugs that are less toxic. With the above activities, the company is trying to discover ways of preventing diseases. Thus, SignaBlok must engage in more drug targets to succeed in their set objectives.

Organisms involved in more drug Targets

In drug target, different organisms are involved in discovering the intended protein. The enzymes are individual targets that help in understanding the environmental risk; they make it possible to identify species, which are sensitive to some pharmaceuticals (Jagath, Bertil, & Gwenn 2007, p.211). Their results can help in interpreting any ecotoxicity data. Gene orientations in a person also help in designing drugs that have less side effects and prescribing of the right drug. People have different gene profile. This, therefore, helps to treat diseases at the early stages.

Technology used in drugs target

New disciplines, bioinformatics and genetics and chemical genomics, have emerged. Here, analysis of the interactions of small molecule proteins takes place in global fashion to ensure that all proteins in the genome take place. With most proteins not taking part as drug targets, only a subgroup will be of pronounced importance. Remarkably, chemical genomics can change the cellular function using the small molecules that look like drugs; for instance, the modified nucleic acids. In spite of this scenario, technologies such as Small interfering RNA (siRNA) allow genes to be eliminated selectively at a high throughput fashion (Zanders n.d). Of late, technological developments have enabled the genome arrangement for easy drug target detection in the pipeline thus facilitates clinical advancement. Present identification of targets focuses on proteins that human beings have encoded and their interaction pathways. Some of the technologies involved in target validation are as below:

Small interfering RNA (siRNA): Researchers use this technology in selective ablation of genes. A very sophisticated technology can knock out mammalian genes from their cells at a high throughput. Research has indicated that siRNA can be drugs. Small interfering RNA is an important complement of chemical genomics and genetics hence can are helpful in target discovery. On the other hand, there is no guarantee of true selectivity of gene ablation. Another technological method is the data mining technology, computer algorithms and hardware. This method has aided information extraction experiments of high throughput. It is widely used in systems biology approach in which parallel measurement of parameters is required in identifying targets. Gene sequencing applies in screening single-nucleotide polymorphisms (SNPs). It performs wide scans on genomes for mutations corresponding to a given disease, and analyses mutations in targets for drugs that are well known (Zanders n.d).

X-ray crystallography, NMR, in silico protein modeling: researchers apply this technology in analyzing the structure of proteins (Zanders n.d). With many structures of proteins, the main objective of the technology is to accomplish high throughput. It determines all the structures, with or without bound ligands. The other technology is the protein separation and analysis; for example, mass spectrometry. This method is identifying proteins and do analysis the modified post-translational. Pharmacologists identify the proteins from mixtures like that of blood, which requires complex modes of separation and sensitive techniques. To analyze proteins in their original form, it is important to identify components like glycosylation. Lastly is the novel synthesis procedure. Researchers use it in chemical drugs as it helps to maximize chemical diversity.

Ethical implications

Companies and groups involved in unearthing more drug targets, constantly faces ethical dilemmas. The first aspect is the allocation of the limited resources. Some people are of the idea that most of the global funds should be used to solve severe and urgent cases, such as access to clean water and famine eradication instead of focussing on indication of genes as a predisposition to various diseases and finding cures (Barash n.d). This group are in contention that this is an act of resource misallocation. On the other hand, pharmacogenomics agree that the Human Genome Project is of immense benefits to patients and the entire health sector. The fatal drug reactions that cause deaths among patients further complicate this scenario. The variation in the genes is the major reason for the adverse reactions. Therefore, pharmacologists should do prior tests on people to ascertain these reactions before administering the drugs. In addition, some of these medicines cause harmful reactions, but non-fatal yet medical practitioners take oaths not to harm individuals (Barash n.d). Lastly, the issue of administering one drug to different people is risky, as no individual safety is not put under consideration.

The next ethical issue is the fair distribution of benefits and burdens globally. With a lot of resource-usage in finding more drug targets, the final drug will be costly. As a result, the drug will be inaccessible to some group of people in the poor regions. This poses a serious challenge to the researchers, who want to get profit from their venture. Further, there exist competitions among companies carrying out research in this sector. This ‘battle’, in the end, will only compromise on quality. This case is rampant in companies where researchers have put their investments. There have also been cases where patients who have devoted their time and bodies in the research did not receive medical benefits because they could not meet the therapy cost. For instance, people who were suffering from Gauchier Disease and the Canavan’s Disease Support Group (Barash n.d).

Another ethical subject that faces the research groups and companies is the invasion of medical autonomy and privacy. World over, going against a person’s right is a violation of the law. A case example, a child in the US joined a genetic research study. The research required the child’s family history to help provide optimal care to the child. At one point, the father found a letter that the facility addressed to the child; the letter indicated that for research purposes, the father’s medical history usage was mandatory (Barash n.d). The information outraged the father who later informed the Office for Human Research Protections (OHRP), of the U.S. Health and Human Services Department. The OHRP sided with the father, and stopped the child using the father’s details arguing that this amounted to violation of personal medical privacy. Such cases challenge the researchers. Therefore, there is need to understand the weighty values given first priorities thus help to know whose right predominates the other. Finally, the ethical subject has been controversial in the discovering more drug targets since it involves gene testing, it amounts to discrimination. Moreover, the test does not take into consideration the environmental factors, eating habits and lifestyles.

Major problems

In discovering more drug targets, researcher faces varied problems. The first problem is lack of incentives for these companies producing many pharmacogenomic products. This undertaking costs many dollars to reach the market (Pharmacogenomics: Medicine and the New Genetics 2011, September 19). Consequently, most companies do not venture in more drug target exercise. They resort to “one size fits all” method to develop drugs. The second issue is education of health care providers on proper drug prescription. With more drugs in the market treating the same condition, complication is bound to occur in drug dispensation. Physicians must go an extra mile to understand the drug diagnosis procedures to different patients, and understand genetics in totality. These help to avert wrong diagnosis and drug prescriptions.

Additionally, limited knowledge on gene variations affecting drug response is another problem. Many genes always influence response therefore, to get the picture upon the impact in genes variation is difficult and time consuming (Pharmacogenomics: Medicine and the New Genetics 2011, September 19). Furthermore, identifying and analysing SNPs, and determining their role in drug response is challenging. If alteration of a single nucleotide in the genome takes place, SNPs, DNA sequence variation, also occur (Pharmacogenomics: Medicine and the New Genetics 2011, September 19). There are also few drug substitutes available to treat specific conditions. In case of gene variation in a patient, the patient cannot use the drug, as there will be no treatment alternatives. There is urgent need to address these problems for instance, governments and non-governmental organizations should offer incentives to the companies and groups involved in more drug target research.

Real benefits

The varied benefits that come with research on drug targets are felt in all the sectors in the society. The first benefit is the discovery of specific drugs. An in-depth study of the gene enables pharmaceutical companies to create powerful medicines targeting specific enzymes and proteins (Pharmacogenomics: Medicine and the New Genetics 2011, September 19). When drugs produced are targeting specific diseases, cases of wrong prescription will decrease. This will also minimize damage to healthy body cells. Additionally, safe and better drugs will be available at the first instance. This is possible as doctors will only analyze the genetic information of a patient and correctly prescribe the right drug at the first time (Pharmacogenomics: Medicine and the New Genetics 2011, September 19). The guesswork method of deciding on the right drug to prescribe will be gone. This will not only eliminate chances of adverse infections and deaths but also quickens recovery time.

The third benefit is manufacture of risk-free vaccines. Vaccines made from DNA will boost a person’s immune system and not cause infections. These vaccines are affordable, stable, and can carry several pathogens at ago. In addition, people can do screening of diseases at advanced levels (Pharmacogenomics: Medicine and the New Genetics 2011, September 19). With adequate information on genetic codes, a person can make necessary environmental changes to negate the adverse effects of genetic diseases. At the same time, there will be a reduction in the cost of healthcare. For example, in TB treatment, the length of time when a patient is on medication will reduce with the coming of effective therapy. The patient will not purchase trial and error drugs but the specific one. These varieties of drugs reduce the cost of healthcare. Another benefit is effective ways of drug prescription. Other than using ages, the doctors will use the rate at which a body process drugs and duration of metabolism.

More drug targets are more helpful to the society in general. Although it faces ethical challenges in the entire process, this should not overshadow the immense benefits. Philanthropists, non-government bodies, and governments should support the research process.

References

Barash, C. I n.d., Ethical Issues in Pharmacogenetics: ActionBioscience – promoting bioscience literacy, Web.

Chen, X., Ji, Z., & Chen, Y. 2002, ‘TTD: Therapeutic Target Database’, Nucleic Acids Research, vol. 30, no.1, pp 412-415. viewed 8 September 2012, via Nucleic Acids Research database.

Drug Discovery Research – Signablok n.d., Web.

Imming, P., Sinning, C., & Meyer, A 2006, ‘Drugs, their targets and the nature and number of drug targets’, Nature Reviews Drug Discovery, vol. 5, no. 10, pp. 821-834. Web.

Jagath, R C, Bertil, S., & Gwenn, V, 2007, Pattern recognition in bioinformatics second IAPR international workshop, PRIB 2007, Singapore, October 1-2, 2007: proceedings. Springer, Berlin.

Jeffrey Conn Research Group n.d., Web.

Metabolic Solutions n.d., Web.

Pharmacogenomics: Medicine and the New Genetics 2011, Web.

Promising new drug target discovered for treatment and prevention of heart failure 2012, Web.

Ying, Z. 2012, Drug Resistant and Persistent Tuberculosis: Mechanisms and Drug. Web.

Zanders, E. D. n.d, ‘New Drug Discovery Technologies’, Innovaro Pharmalicensing. Web.

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