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University of Manchester - Articles and news items
New STELARA® (ustekinumab) five year data show consistent efficacy and safety profile in treatment of moderate to severe plaque psoriasis
New efficacy and safety data…
Identification of protein biomarkers and the evaluation of changes in protein expression following drug treatment rely on both the generation of peptides from cellular proteins, and the acquisition and interpretation of spectra generated by tandem mass spectrometry (MS/MS). Acquisition of MS/MS spectra in a datadependent manner means that a significant number of the protein fragments (peptides) generated are never actually subjected to MS/MS1. Moreover, only a small proportion of acquired MS/MS spectra are ever interpreted, despite the large number of tools for the automated analysis of such data. Furthermore, many fragment ions are simply ignored during data analysis, in large part because automated search engines do not ‘look’ for all potential fragmentation products, and also because we simply still do not sufficiently understand the mechanisms of gas-phase peptide fragmentation to fully interpret the spectra (most likely a combination of the two). The end result is that even though proteome coverage is increasing in large-scale analyses, we are still a long way from the ideal of ‘complete’ proteome analysis.
Imagine that you are part of a small biotech company, BiotechCo, whose business is the development of delivery systems for pharmaceutical products. One of your team, who is in charge of developing sales with a large pharmaceutical company, Pharma Co, came to you three months ago with the possibility of a very interesting contract within that company. You went to a meeting where various things were discussed on a confidential basis. As a result of that, you now have a clearer idea of where the pharmaceutical company is aiming to take an important drug, which is approaching the end of its patent life. If BiotechCo can come up with a new improved delivery system, then you will assist Pharma Co in creating a significant market lead for their drug, and by so doing probably increase the chances of selling your portfolio of technologies to Pharma Co. You have set your best research brains on to the problem, and they have come up with a very clever device which uses technology that has been known outside the pharmaceutical sector for a non-medical purpose. Their developments have been reported to Pharma Co on a confidential basis and Pharma Co has been given a prototype. Pharma Co has done some tests on the device.
Toxicology is the study of the harmful interactions between chemicals and biological systems. Man, as well as other animals and plants, is increasingly exposed to a huge variety of chemicals. These range from metals to large complex organic molecules, all of which are potentially toxic. A toxicologist must understand pathology, biochemistry, chemistry and physiology as these disciplines all contribute to the impact of a given chemical’s toxicity. Indeed the multidisciplinary nature of toxicology makes the area of toxicology a challenging yet rewarding area for research and learning. To gain a true understanding of how a chemical can disrupt a biological system and cause toxic consequences is no easy matter.
Cancer molecular pathology broadly relies on the comparison between diseased and normal tissues, with statistically validated differences revealing cancerassociated pathways. This approach, although comparatively one-dimensional, has been remarkably successful, enabling identification of many types of malignant biomarkers and providing the means to develop pharmaceutical agents directed against pertinent biological targets. Most typically during the progression of malignancies, pathologists employ morphological screening of cancerous tissues. However, this form of monitoring has significant limitations, particularly in the early stages of pre-treatment or during the clinical remission.
The pharmaceutical industry continues to experience a high attrition rate during the latter stages of small molecule therapeutic development, most disappointingly during the late, and highly expensive stages of Phase II and Phase III trial1. If left unchecked, it is likely that this late-stage failure in drug development will only increase the already staggering cost of getting pharmaceuticals to market. The failure of drugs at this stage in development occurs primarily because of problems with toxicity and/or failure to produce a significant effect in whole animal models (lack of efficacy)1. The increasingly popular approach of systems biology is perceived by many as a potential solution for overcoming these problems, enabling the design of effective, safe therapeutics on a realistic R&D budget.
Biotechnological expertise is becoming increasingly important within the pharmaceutical industry, and will play a pivotal role in the monitoring of fermentations, particularly their optimisation within the framework of Process Analytical Technologies (PAT). The ability to harness biological processes for the development of drug therapies, so called ‘biopharmaceuticals’ provides treatments that range from small molecule antibiotics to large recombinant proteins. Typically, synthesis of these drug products is enabled through the exploitation of bacterial, yeast, mammalian or plant cells. One of the earliest examples of protein biopharmaceuticals was the use of recombinant DNA technology to modify ‘Escherichia coli’ for the production of Human Insulin, which was followed by the development of Human Growth Hormone and Human Blood Clotting Factor1.
Raman spectroscopy is a highly versatile tool that provides chemical fingerprints from biological material that can be interpreted using chemometrics and machine learning. In combination this powerful approach is being developed for the quantitative determination of multiple determinands in bioprocesses and for the characterisation of microorganisms.