BB&T National Editors

Short of autopsy and the examination of a deceased's brain, there is no definitive determination of Alzheimer's disease only an informed guess concerning a group of symptoms.

In what may be the achievement of this important goal, or simply another elusive grasping, Power3 Medical (Houston) in mid-August issued a preliminary report on a 300-patient study indicating the identification of Alzheimer's in 95% of cases.

The company provided what it termed a "status report," saying that its NuroPro test using protein biomarkers in blood serum has been confirmed as having the ability to identify Alzheimer's in a large majority of cases in a 300-patient study.

That validation is "north of 90%," Steven Rash, CEO of Power3, told Biomedical Business & Technology, saying that the data looked at thus far in the study offers "wonderful news" for the company and "better than anticipated."

Well, maybe.

Even if the data ultimately demonstrates the 95% accuracy, some may question the study protocol the use of a control group, not of individuals deceased and autopsied as having Alzheimer's, but defined by a clinical expert as having the disease.

Rash said that the company is comparing its biomarker analyses "with the clinical diagnosis" of patients made by Dr. Marwan Sabbagh, director of clinical research at the Cleo Roberts Center of Clinical Research of the Sun Health Research Institute (Sun City, Arizona), lead investigator in the study. The company said it plans to publish the final data from the 300-patient study before the year is out and then begin commercialization.

Whether highly positive data from the study will convince customers of the test's validity is likely mostly a marketing question, since the company does not have to seek FDA clearance. FDA okay is unnecessary, Rash noted, since the test initially won't be sold to other labs for analysis but will be analyzed in the company's own CLIA-certified laboratory. However, he said that the company has begun discussions with the FDA, as a matter of seeking "guidance," and that longer-term plans call for negotiating the agency's hoops and hurdles to enable broader use of the test.

The test uses protein biomarkers, with Rash emphasizing that the company analyzes a "panel" of these for determination of Alzheimer's as well as Parkinson's. He said the company uses 59 biomarkers, with a variety of patent applications for them in the works, but "I can't tell you the name of them." They are "differentially expressed from the norm," that work "in tandem with one another," he said, and then analyzed by the company's system to create a disease profile.

Study leader Sabbagh reported that 92 Alzheimer's and control patient samples have been analyzed in Power3's laboratory, demonstrating high sensitivity and specificity in the diagnosis of Alzheimer's.

Dr. Essam Sheta, director of Power3's laboratory, said that the data from the 300-patient study so far shows the test's "superior sensitivity and specificity with results in the 95% range."

Rash said that the company also is pursuing an ongoing Parkinson's validation study under the direction of Dr. Katerina Markopoulou at the Research Institute at the University of Thessaly (Thessaly, Greece). It said it expects to conclude the Parkinson's study this month and publish the results soon after.

Elsewhere in the product pipeline:

Cangen Biotechnologies (Baltimore), with collaborator Dai Nippon Printing (DNP; Tokyo), is developing a blood-based assay to fill the lung-cancer screening and, perhaps diagnostic, void involving early stage lung cancer. The assay already has shown promise in a 1,000-patient sample study. "This is a pretty simple test that uses the DNP proprietary purification systems," Cathy McDermott, RN, vice president of regulatory affairs and technical development at Cangen, told BB&T. "The beauty of this test is that it could be performed anywhere without sophisticated equipment." Cangen's technology uses matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectroscopy to discover the lung cancer-specific biomarkers. McDermott said Cangen executives are currently trying to decide whether to develop the test for screening, as a diagnostic or for both. "Initially, we're looking at using this test as a screening tool for high-risk patients such as smokers and for some patients with certain types of occupational exposure," she said. "Because it's a blood test, it has very good potential utility by primary care physicians or internists." These doctors would use it for all high-risk patients as a normal course of physical exams. McDermott said the intention is to catch lung cancer at the earliest stages, I and II, as was proven during the sample study at multiple sites in South Korea. "Our next stage in this process is to negotiate with the FDA for an actual trial size," she said, adding the company hopes to have the same number of patients included, "at a minimum." If all goes well, McDermott said the trial could begin in 2009 and be completed in 2011. "We would hope to be on the market late 2011 or 2012," she said.

Canica Design (Almonte, Ontario) a research and development company, has been awarded its first U.S. patent in a series of comprehensive U.S. and international patents that it said "dramatically advance" the management and closure of wounds of all kinds. The multinational patent portfolio covers Canica's clinical and surgical system and method for moving and stretching skin and muscle. A decade ago, wound management was revolutionized after the licensing of patents awarded to Wake Forest University (Winston-Salem, North Carolina) researchers, which enabled the mass commercialization of negative pressure wound therapy (NPWT) and created what has grown to become a multi-billion-dollar market led thus far by Kinetic Concepts (San Antonio). Leonard Lee, president of Canica, notes that like NPWT a decade ago, Canica's dynamic wound closure system is another classic business school study in disruptive technology. "It undermines the business model behind most current products that focus on the prolonged and laborious process of managing a wound while it heals. In comparison, dynamic wound closure focuses on rapidly closing the wound, leaving nothing to manage. This is certainly disruptive to all those companies whose profits are generated by the cumulative sales of wound management consumables."

Cook Medical (Spencer, Indiana) said it has received FDA approval to market its Zenith Abdominal Aortic Aneurysm (AAA) Iliac Flex Legs and Z-Trak introduction system, made for use with the Zenith Flex AAA endovascular graft. The products are designed to improve flexibility and conformability in the aorta and iliac artery, a tortuous section of patient anatomy, for patients undergoing endovascular aneurysm repair (EVAR), Cook said. The Zenith AAA Flex Leg external stents are shorter than those of Cook's previous offering, with increased gaps between the stents reducing the potential for the leg to kink, the company noted. The Flex Leg and Z-Trak system is available in the U.S. as well as in continental Europe and the U.K. The device, like the Zenith Flex main body, is constructed of polyester graft material supported by stainless steel Z-stent bodies. According to John Foster, a global product manager for Cook, the Zenith Flex endograft main body with Flex Leg stents "represents an important engineering achievement in the pursuit of improved outcomes for patients undergoing EVAR. The body is very variable, everyone is a little different. As a result, [flexibility and conformability has] always been an area in the AAA market where we do try to seek improvement." Cook says its Z-Trak introduction system provides an integrated interface to the company's AAA platform, continuing its established maneuverability for "precise, controllable device orientation and deployment" of the company's endovascular stent graft.

• In order to reduce the number of medical complications due to errors in injections, Covidien (St. Louis) has launched what can be called a "smart" syringe. Utilizing radio frequency identification (RFID) with its Ultraject prefilled contrast media syringes and its Optivantage DH power advantage, the company has developed a syringe that will not shoot an injection if there is an incorrect dosage. "RFID is a fairly mature and well-known industry," Jeff Lockwood, director of marketing for imaging devices at Covidien, told BB&T. "[But] RFID is new to this particular technology." The RFID-enabled system Covidien uses creates an intelligent interface between the contrast media syringe and the power injector that helps radiology technologists to better ensure that each patient receives the prescribed concentration and programmed dose of a contrast media-related drug during a procedure. The interface allows the injector to physically alter the RFID label on a syringe once it is used, which can substantially reduce the probability of life-threatening air injections or air embolisms caused from using an empty, used syringe. It also helps reduce the potential for infection from cross-contamination by automatically preventing the injection of contents from a previously used RFID-labeled syringe in another patient exam. Covidien's system also indicates if the drug in an RFID-labeled syringe is past its expiration date. "Let's say if there is an incorrect contrast in the syringe, it will not shoot the injection," Lockwood said. "It will not allow the technologists to go ahead with the procedure." A warning also comes up in the form of a pop-up screen on the syringe and on a computer screen. The company said the RFID tag changes after an injection is made so it's not possible for a used syringe to be reused. It automatically rejects it. The system also automatically transfers drug and achieved exam protocol information onto a printed label for the patient record, which reduces the need for manual data entry, thereby improving efficiency and accuracy. Plans call for it to be further modified at some point to allow for data transfer directly to electronic medical records.

Echo Therapeutics (Franklin, Massachusetts) has reported positive results of a clinical study of its Symphony Transdermal Continuous Glucose Monitoring (tCGM) System in patients with Type 1 and Type 2 diabetes and will now sprint to conduct pivotal studies in early 2009, with expectations of filing a PMA with the FDA by mid-2009. The non-invasive Symphony tCGM System consists of wireless transmission and transdermal biosensor technologies, and the Prelude SkinPrep System, which incorporates needle-free skin permeation control. The Prelude sensor sits on top of the skin, which is prepped through gentle dermabrasion or an ultrasound based method. The system is designed to provide both diabetics and hospital patients with a reliable, affordable, comfortable-to-wear, easy-to-use and needle-free continuous glucose monitoring device. "Blood glucose measurements should become the fifth vital sign," Echo Chairman/CEO Patrick Mooney, MD, told investors during a conference call. "Diabetic complications are the result of patients not keeping tight control over their glucose levels. Physicians acknowledge that more frequent testing will lead to better outcomes." Using 1,292 reference blood glucose measurements from the 10 subjects in the study, Clarke error grid analysis of the study data showed that Echo's system had approximately 99% of the data in the combined A/B zones, with 76.4% in the A zone and 22.4% in the B zone, and only 0.2% and 0.9% in the C zone and D zone, respectively.

Health Discovery Corp. (HDC; Savannah, Georgia) reported that it has a new gene-based test, this one for prostate cancer, that has successfully completed a Phase III double-blind clinical trial. Results from Phase I, Phase II and Phase III double-blind clinical validation studies now completed with prostate tissues obtained from multiple sites — including those tested in collaboration with MD Anderson Cancer Center (Houston) — demonstrated a high success rate for identifying the presence of Grade 3 or higher prostate cancer cells (clinically significant cancer), as well as normal and benign prostatic hyperplasia (BPH) cells. To date, 322 prostate tissues have been tested, according to the company. And the combined results of the recently completed double-blinded clinical validation studies demonstrated that the gene-based test achieved a sensitivity of 90% for correctly identifying the presence of Grade 3 or higher prostate cancer cells, and a specificity of 97% for correctly identifying non-cancer cells (normal and BPH), representing an overall test accuracy of 93%. "We ... are excited to have our first revenue-producing molecular diagnostic test ready for commercialization," said CEO/chairman Stephen Barnhill, MD. "The successful development, validation and commercialization of this new molecular diagnostic test for prostate cancer proves that HDC, by combining our patented SVM and SVM-RFE technology and our expert Scientific Team, has the ability to produce new molecular diagnostic and prognostic tests which are the future of personalized medicine." The new test will be performed at Clarient's (Aliso Viejo, California) clinical laboratory, with HDC receiving a 30% royalty on each test performed.

• A test developed by Pathwork Diagnostics (Sunnyvale, California) that can help healthcare professionals determine what specific type of cancer cells are present in a malignant tumor has been cleared by the FDA. The Pathwork Tissue of Origin Test uses a microarray to measure the expression pattern, comprising more than 1,500 genes, in the uncertain tumor and compares it to expression patterns of a panel of 15 known tumor types, representing 60 morphologies overall to help determine the tumor's origin. "It took three years to develop the test," David Craford, VP of commericial operations for Pathwork, told BB&T. "This test represents a real milestone for expression-based molecular diagnostics. The feedback we've gotten is positive, and oncologists have said that they were happy [this helps] get them to a stronger diagnosis." In the validation study submitted to the FDA, the test demonstrated 89% positive agreement (akin to sensitivity) with available diagnoses and 99% negative agreement (akin to specificity). The study consisted of the analysis of 545 metastatic, poorly differentiated and undifferentiated tumors that had been identified as one of the 15 tumor types on the panel using existing methods. The test demonstrated an average 94% overall concordance across four laboratories in a cross-laboratory comparison study of 60 metastatic, poorly differentiated and undifferentiated tissue specimens. The test is administered through a tissue biopsy. Pathwork's software converts the scanned image data to gene expression measurements. The gene expression patterns then are compared with known gene expression patterns in the database that correspond to different tumor types.

QualSec (North Logan, Utah) is developing the Nano-Nose, a device unique in many ways, but importantly able to analyze streaming air rather than just lab-controlled air samples. Incorporating the miniaturized finesse of nanotechnology, the result is a lightweight, hand-held machine that requires no special training, offers refined sensitivity and the ability to perform hundreds of tests consecutively. J.E. Hand, QualSec's CEO, said the Nano-Nose uses photonic energy that bounces off of quantum dots, quantum dots being nanometer-sized semiconductors made of cadmium selenide, cadmium sulfide or cadmium telluride with an inert polymer coating. Because of their small size, quantum dots can function as cell- and even molecule-specific markers that will not interfere with the normal workings of a cell. "They react to a laser light source and recording source that measures the reaction of the dot," Hand said. "We get a measurement of the presence of the element and the density instantaneously. The potential medical applications are vast. Virtually any communicable disease as well as certain chronic diseases, such as lung cancer, could all be detected with the Nano-Nose. He said QualSec is developing the Nano-Nose for a variety of uses, with medical and homeland security ranking at the top of applications out of the gate. But he's cautious about surfing the unfamiliar FDA regulatory waters. "We wouldn't yet strive to be a diagnostic tool, due to FDA constraints. We will offer it instead as a screening tool, first for tuberculosis," Hand said. The company will seek collaboration or partnership with an established med-tech company, one willing to shepherd the Nano-Nose through the regulatory turbulence. QualSec tested a benchtop prototype last year that fit inside a briefcase. But now the company is developing a hand-held model the size of a CD player.

Rosetta Genomics (Rehovot, Israel) is seeking to validate its microRNA-based test designed to identify the primary site of cancer of unknown primary (CUP). The company has initiated a clinical validation study of its CUP assay with the University of Texas M. D. Anderson Cancer Center (Houston). The validation study will include 100 patients who are diagnosed with CUP at M. D. Anderson. Rosetta expects to submit this test for regulatory approval later this year. "The initiation of this validation study is an integral part of the commercialization roadmap for our diagnostic tests, as we advance them toward use in a clinical setting," said Amir Avniel, president/CEO of Rosetta Genomics. "We believe the initiation of this study for our CUP assay with a leading cancer research center such as M. D. Anderson attests to the critical unmet need this test addresses." Treatment that is specific to the type and location of the primary tumor is more likely to be effective, according to the National Cancer Institute. Rosetta says patients with CUP pose a therapeutic dilemma and treatment is often empiric with a "trial and error" approach. Quicker and more accurate methods of identifying the tissue of origin of CUP cases would permit the use of these therapies, thereby improving the chances of achieving a response and possibly extending the patient's survival, the company said.

Royal Philips Electronics (Amsterdam, the Netherlands) has unveiled a series of portable, compact patient monitors that provides a reliable, yet affordable means to observe and care for patients. Now available to healthcare providers in India, the new Philips SureSigns VM3 is the first Philips patient monitor designed for emerging markets. "The SureSigns VM3 leverages the high-quality platform of Philips' industry leading patient monitoring portfolio," said Anjan Bose, Philips Healthcare India (Hyderabad) senior director and business head for India, Bangladesh, Sri Lanka and Nepal. He added, "Combining advanced software and technology in a compact economical package, the VM3 is the perfect solution for caregivers across the wide variety of clinical environments we see here in India." The SureSigns VM3 offers ECG, respiration and pulse oximetry in a compact monitor that helps provide quality care in almost any clinical setting, according to the company.

• Researchers at the University of California Los Angeles (UCLA), working via a $12.5 million grant from the National Institute of Dental and Craniofacial Research, have developed an ultra-sensitive optical protein sensor, a first for a salivary diagnostic test. Chih-Ming Ho, PhD, and his UCLA team report that the sensor can be integrated into a specially designed lab-on-a-chip, or microchip assay, and preprogrammed to bind a specific protein of interest, generating a sustained fluorescent signal as the molecules attach. A microscope then reads the intensity of the fluorescent light a measure of the protein's cumulative concentration in the saliva sample and scientists gauge whether it corresponds with levels linked to developing disease. "The biggest challenge is that the biomarkers in saliva are at very low concentrations compared to blood, so we need a highly sensitive sensor," Ho told BB&T. "Because saliva contains all the same markers found in blood, in principal, you could detect many of the diseases that you can in the blood. Our first task is to try to detect oral cancer and we have proved that it is possible." In their early experiments, the researchers primed the optical protein sensor to detect the IL-8 protein, which at higher than normal concentration in saliva is linked to oral cancer. Using saliva samples from 20 people half healthy, the others diagnosed with oral cancer the sensor correctly distinguished in all cases between health and disease. The sensor achieved a limit of detection for IL-8 that is roughly 100 times more sensitive than the current blood-based ELISA tests, the gold standard technique to measure protein in bodily fluid.

• Researchers at the University of Utah School of Medicine (Salt Lake City) and colleagues at UCLA may have found a way to make it easier to diagnose anemia related to chronic illness, as well as diseases of iron overload. According to the researchers, iron balance in the body is regulated by the interaction between a liver-produced hormone called hepcidin and the iron transporting receptor ferroportin. Hepcidin binds to ferroportin resulting in decreased export of iron out of cells. An excess of hepcidin in the blood can cause anemia and a deficiency of hepcidin causes a build-up of iron that is damaging to body organs. Both anemia and iron overload have various causes, so it is often difficult to distinguish among those causes. "It is hard to diagnose the anemia of chronic disease," said the study's senior author, Jerry Kaplan, PhD, University of Utah professor of pathology and assistant VP for research at the University of Utah Health Sciences Center. "Having an assay for hepcidin would make it much easier and it would also help in diagnosing iron overload diseases." The research was published in the August issue of Cell Metabolism.

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