NORWICH, UK – Recent efforts to optimize metabolomics technology are beginning to bear fruit in the discovery of novel biomarkers for disease. In general, the concentrations of metabolites are amplified relative to the proteins that prompted their formation, making them potentially more sensitive, both in diagnostics and as drug targets, than protein biomarkers.
“Metabolites are downstream from the protein, so you must have an amplification in concentration,” Douglas Kell, director of the Manchester Centre for Integrative Systems Biology, said here at the British Association Science Festival in August. “Furthermore, you don’t need to know the gene sequence; there are fewer metabolites than proteins, and they are generic, so once you can measure a metabolite, it is the same in every organism – which is not the case for proteins.” It has been estimated that there are about 3,000 metabolites in the human metabolome. The issue is that there is a wide concentration range and it is difficult to detect metabolites that occur at low concentrations.
Kell’s group has developed an automated “robot scientist” that couples gas chromatography separation to mass spectrometry detection, and has optimized and refined the equipment to the point where it can discriminate 1,800 true metabolites. Using the robot, blood samples from healthy and affected individuals have been analyzed to systematically uncover subsets of metabolites that are markers of particular diseases. For example, examining samples from women affected by pre-eclampsia in pregnancy and those who were not led to the discovery of three metabolites that distinguish sufferers. “None of the [three metabolites] was visible [with our equipment] when we started; it is only as we improved the process that they were detected,” Kell said.
Currently, pregnant women are sifted out as being at risk of pre-eclampsia by measuring blood pressure. “But this is more than a surrogate for blood pressure: You can look in the affected cohort only and follow the development of the disease,” Kell said. More recently his group has found further metabolites linked to pre-eclampsia, making the biomarkers potentially even more sensitive.
Kell has discovered metabolites for Huntington’s disease and for a number of cardiovascular diseases, also. “Many of these offer the possibility of novel interventions and of prognostic detection of diseases in their earliest stages, before they become life threatening,” Kell said.
Blue spectrum light targets cancer
Canadian and U.S. research agencies are joining forces to promote early diagnosis of oral cancer through research into a device that uses high-energy blue spectrum light to spot the disease. The National Institute of Dental Craniofacial Research is so impressed with the VELscope, it has given the B.C. Cancer Agency (BCA) and Simon Fraser University (Burnaby, British Columbia), a $2.5 million grant to fund an oral cancer-screening program using the device. “The idea is to try and catch oral lesions that might turn into cancer that can’t be seen through conventional examination,” BCAA research scientist Dr. Calum MacAulay told BB&T. “Those lesions are visible using this fluorescent visualization device.”
Oral lesions are typically discovered by dentists during routine examinations or by family physicians, who then refer the patient to an oral specialist. By the time a lesion is large enough to be detected by the naked eye, however, it may be too late. About half of all cancerous oral cavity lesions in North America detected by conventional oral examination are late stage, so that, on average, half the patients will die within five years.
Miriam Rosen, director of the BCAA’s Oral Cancer Prevention Program, told BB&T that clinicians have not been able to identify changes in the oral cavity that might be a precursor to cancer. “So any new devices that provide a better view of changes are really important from the standpoint of undertaking an effective intervention against disease, to prevent its development. They’re also important from the standpoint of preventing its recurrence,” Rosen said.
The VELscope works by shining high-energy blue or fluorescent light onto suspect tissue. Healthy tissue will emit a green color, while potentially pre-cancerous tissue “loses the green color and goes to a dark shadow,” a color change Rosen said is associated with changes “to both the biochemical composition and the morphology of the tissue.”
Abbott opens new facility in Ireland
Abbott Laboratories (Abbott Park, Illinois) reported continued expansion of its Abbott Vascular sites in Ireland with the opening of a new 180,000 square foot manufacturing facility in Clonmel. The company also unveiled architectural drawings for an additional 70,000 square foot administration, warehouse and logistics facility to accommodate future growth in Clonmel.
“Expansion to accommodate new facilities and additional personnel is necessary as we develop and deliver the highest-quality lifesaving devices and treatments for vascular disease — particularly in emerging therapies such as drug-eluting, carotid and bioabsorbable stents,” said Pat Ryan, vice president, Manufacturing Operations, Cardiac Therapies.
Abbott said the Clonmel and Galway sites play a key role in its drug-eluting stent (DES) manufacturing operations. It said it plans to initiate European launch of its first DES, the Xience V everolimus-eluting coronary stent system, next month. Abbott is awaiting CE Mark approval for its ZoMaxx DES.
Abbott’s Galway operation was also recently granted planning permission to build a new 150,000 square foot facility which will include manufacturing areas, warehousing, laboratories, and a three-story office accommodation.
Reuse of instruments spreading vCJD
A study published in the online edition of the Journal of the Royal Society Interface has been exploring the likelihood that varient Creutzfeldt-Jakob disease (vCJD) might be spread via the reuse of surgical instruments, and calls for more data in order to allay fears over the possible transmission of vCJD. The number of vCJD cases continues to decline, and it is believed that most cases to date are the result of consumption of BSE-infected beef. There were 161 recorded cases by the end of 2005, and the annual incidence has been decreasing steadily since 2000, with estimates that the total scale of the epidemic through this route now lie in the low hundreds.
However, concern has been raised that transmission could, in theory, occur directly from one person to another via routes such as blood transfusions and surgical operations, despite instruments being decontaminated routinely before being used.
Scientists based at both the London School of Hygiene & Tropical Medicine and the National Creutzfeldt-Jakob Disease Surveillance Unit at Western General Hospital (Edinburgh, Scotland) decided to explore this possibility.
The results, published online by the journal, show that key factors determining the scale of any epidemic are the number of times a single instrument is re-used, combined with how infectious contaminated instruments are and how effective the cleaning is.
The authors begin by presenting data on the surgical procedures undertaken on vCJD patients prior to the onset of clinical symptoms that support the hypothesis that cases via this route are possible. They then apply a mathematical framework to assess the potential for self-sustaining epidemics via surgical procedures. They conclude that further research is needed into how surgical instruments are used so as to reduce uncertainty and assess the potential risk of this transmission route.
Researchers said, “Given the frequency of high- and medium-risk surgical procedures undertaken in the UK, a range of plausible scenarios suggest that surgical procedures could provide a potential route for a self-sustaining epidemic of vCJD.”
They added, “A first step to reducing the current uncertainty in the potential for self-sustaining transmission via surgery would be to survey the frequency with which different instruments are used, particularly those used on high-infectivity procedures. Also, tracking of surgical instruments should be improved, so that, at the very least, instruments are not re-used once the infection status of a patient is known.”
Viacortis engenders tissue-viability process
Viacortis, a EUREKA project being carried out in Lithuania, has developed new techniques to monitor the viability of heart tissue during heart surgery, so that cardiac surgeons have a real-time, comprehensive indication of how the heart is reacting.
A current trend in cardiac surgical practice is to work with an actively beating heart, rather than the more usual suppression of heart activity by low temperature. But carrying out surgical manipulation on a beating heart can lead to other problems if blood supply to the heart tissue itself is obstructed.
The Viacortis project has developed three techniques that can be used side by side to give detailed information on the way the heart tissue is coping, so that the surgeon has early warning signals if it is becoming too stressed.
Project coordinator Algimantas Krisciukaitis, MD, of the Kaunas University of Medicine in Lithuania, said, “The novelty of our method is that we developed quantitative criteria to measure heart damage. We can measure the electrical potential of the heart muscle, compare it at the same time with the biochemical activity of the tissue, and map its local heat pattern.”
These three parameters together reveal early and small changes in the functional state of the heart tissue, and their exact location. The researchers said this gives vital information to the surgeon on the extent of tissue damage and the time he has available to complete the procedure.
Viacortis brought together the Biomedical Research Institute and the Heart Center of Kaunas University, plus the Laser Research Center of Vilnius University and Elinta Uab, a small company with expertise in multi-channel analysis of biological signals
A German partner was the Free University of Berlin’s Institute for Medical Physics and Laser Medicine, which developed the equipment to measure fluorescence as an indicator of biochemical activity. The German institute also worked closely with Krisciukaitis’ group in Kaunas to correlate fluorescence with electrical activity.
Because the Viacortis results introduce quantitative measurement of these indicators, they have made it possible to draw up optimum protocols for routine use of a range of surgical methods — showing clearly when urgency is great or when the heart tissue is not under excessive pressure.
The project has successfully demonstrated the use of the triple-monitoring system, which now is ready for further development of the equipment, followed by testing, approval and manufacture, before surgeons can make use of the extra support it can offer.
The results of this development have been published in professional journals and presented at conferences.
“It was useful to be a EUREKA project because it gave us international recognition and government support for the participation of a small company, which worked hard and did great things,” said Krisciukaitis.
Pioneer Surgical introducing Nubac System
Pioneer Surgical Technology (Marquette, Michigan) will introduce its Nubac Intradiscal Arthroplasty System in the European market through its new subsidiary, Pioneer Surgical Technology BV, which will be managed by Dr. Lex Giltaij. Following the introduction of Nubac, Pioneer Surgical Technology said it will grow its product offerings to include Pioneer’s expanding line of spinal and orthopedic devices and support services.
“The founding of our European subsidiary is an important landmark for Pioneer in its goal to become a global player in the spine market,” said Dr. Matthew Songer, president and CEO of Pioneer. “With Nubac we have developed an exciting non-fusion technology designed to preserve spinal motion. Our experiences in Europe have shown great promise for patients suffering from back pain.”
Pioneer said Nubac is “the only intradiscal arthroplasty device for patients with degenerative disc disease utilizing articulating PEEK-on-PEEK material designed to achieve load-sharing and uniform stress distribution under various physiological loading conditions.”
The Nubac procedure is intended to preserve most of the annular tissue while being less invasive than total disc replacement (TDR) and fusion. The Nubac procedure allows further treatment options of TDR or fusion, if revision is required.
Pioneer Surgical began U.S. clinical trials of the Nubac Intradiscal Arthroplasty System for patients with degenerative disc disease as part of its investigational device exemption (IDE) study. Implantations of the Nubac devices under the IDE took place at Marquette General Hospital (also Marquette), last month.
Avitar tests to be used in DRUID Project
Avitar (Canton, Massachusetts), developer of a rapid, on-site, oral fluid-based screening test for drugs-of-abuse, reported that it has been selected to participate in the European Driving Under the Influence of Drugs (DRUID) Project.
Under the DRUID Project, oral fluid screening devices will be tested under operational police conditions by police forces in Germany, Spain, Italy, Belgium, Denmark, and Finland.