Life Sciences Summit Meeting 

Target Health is pleased to announce that it is a Sponsor of the Life Sciences Summit 2009 which will be held on September 23-24, 2009 at the Hyatt Regency Long Island, 1717 Motor Parkway, Hauppauge, New York, USA 11788. Dr, Mitchel will be hosting a panel on “Regulatory Strategic Planning in the Early Stages of Drug and Device Development.” The panel will address pre-IND/IDE activities, pre-clinical and early-clinical regulatory strategies, and the process by which companies advance through and deal with FDA regulations / requirements as well as the evolving regulatory environment. Topics include:

  1. Working with FDA  –  Chris Szustkiewicz, CS Associates
  2. The Nonclinical Process  –  Colleen Johnson, Reno and Associates
  3. The Role of Regulation in Biotech Development – Ron Guido, Pfizer, Inc.
  4. Device Clinical Trials – Mark Citron, TYRX, Inc.

For more information about Target Health and our software tools for paperless clinical trials, please contact Dr. Jules T. Mitchel (212-681-2100 ext 0) or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.

Adult Fat Cells Easily Become Multi-purpose Stem Cells 

New research has been shown that tissue from hip, thigh and belly can be transformed with relative ease into 1) ___ that may one day be capable of repairing a wide range of damaged or diseased tissues. Stem cells found in 2) ___ deposits, it turns out, are more primitive than the many adult stem cells harvested from tissues such as skin and blood, with relatively less effort than is required to make, for instance, a stem cell derived from skin. Fat cells can be reprogrammed to become muscle, neuron and stomach lining cells, finds a new study slated for publication in the Proceedings of the National Academy of Sciences. Fat cells are more embryonic-like than stem cells derived from skin, according to Ning Sun, who conducted the research at Stanford University’s Stem Cell Biology and Regenerative Medicine Institute. Reprogramming adipose stem cells to become “pluripotent” is more efficient as well. Using skin-cell “fibroblasts,” it took about 1,000 cells to yield a single induced pluripotent stem cell, while the same process conducted on 1,000 stem cells from fat yielded 20 induced 3) ___ stem cells. The science of reprogramming adult stem cells to behave more like those derived from human embryos remains in its infancy, including the risk that the use of some reprogrammed stem cells in patients might jump-start the growth of 4) ___. But the search for ways to make adult stem cells perform the same feats of transformation that 5) ___ stem cells do has provided an alternative to those cells, and with fewer ethical drawbacks. For future patients looking to regenerative medicine to repair hearts, brains and diseases of the soft tissues, the new work suggests that their own fat stores could be plentiful workhorses of medical treatment. Because these stem cells would come from a patient’s own body, they are unlikely to be attacked or rejected as foreign intruders by the body’s 6) ___ system. With roughly two-thirds of the American adult population overweight or obese, the US could become a potential future exporter of this promising new resource: “Liquid gold,” as seen by 7) ___. The nation’s ballooning weight problem is expected to be a key contributing factor in rising rates of cardiovascular disease, arthritic joints and cancers — all of which we will look to 8) ___ medicine to cure. If fat cells end up playing a key role in treating fat-related diseases, that may lend new meaning to the maxim “patient, cure thyself.” And it could mean we will need to horde our fat deposits for domestic consumption.

 

ANSWERS

1) cells; 2) fat; 3) pluripotent; 4) cancers; 5) embryonic; 6) immune; 7) liposuctionists; 8) regenerative

Stevia 

Stevia is a plant that may help combat obesity. The species Stevia rebaudiana, commonly known as sweetleaf, sweet leaf, sugarleaf, or simply stevia, is widely grown for its sweet leaves. As a sweetener and sugar substitute, stevia’s taste has a slower onset and longer duration than that of sugar, although some of its extracts may have a bitter or licorice-like aftertaste at high concentrations. As long as 1500 years ago, the Guarani people of Paraguay discovered a native plant with delicious green leaves that had an unbelievable sweetening power. When they chewed just a few leaves or added crushed leaves to hot mate’ (a bitter tea-like drink), the leaves sweetened the drinks. Gradually, they found that this sweet plant they called kaa he-he (which means “sweet herb”) had other uses besides its sugary taste. The natives used this sweet plant for: softening skin, aiding digestion, balancing blood sugar, healing blemishes, sores and wounds and smoothing wrinkles. In 1887, an Italian botanist, Dr. Moises Santiago Bertoni, who was the director of the College of Agriculture in Asuncion, Paraguay, heard his native guides describe a “very strange plant” that had some interesting qualities. Finally, he received a packet of broken kaa he-he leaves from a mate’ plantation in the north and announced his “discovery” of the new species in a botanical journal. Bertoni named the plant Stevia rebaudiana in honor of a chemist named Rebaudi who would later identify the plant’s sweetness component. In 1899, Bertoni first described the plant and the sweet taste in detail. But only limited research was conducted on the topic, until in 1931, two French chemists isolated the glycosides that give stevia its sweet taste. These compounds were named stevioside and rebaudioside, and are 250-300 times sweeter than sucrose, heat stable, pH stable, and non-fermentable. The very first crop of stevia, an entire ton of dried leaves, was harvested in 1908, but it wasn’t until 1931 that stevia became more commercially viable. In the 1960’s, Japan became one of the first countries to use stevia on a large scale. Recent medical research has shown promise in treating obesity and hypertension. Stevia has a negligible effect on blood glucose, even enhancing glucose tolerance; therefore, it is attractive as a natural sweetener to diabetics and others on carbohydrate-controlled diets.

Genes Key to Staph Disease Severity, Drug Resistance Found Hitchhiking Together 

The extreme danger associated with Staphylococcus aureus infections is due to the combination of frequent antibiotic resistance, which prevents efficient treatment, with extraordinary virulence, which determines the severity of disease. S. aureus is known to exchange antibiotic resistance and virulence determinants between different strains, thereby spreading the capacity to cause serious infections in the S. aureus population. One of the ways Staphylococcus bacteria become drug-resistant is through horizontal gene transfer, whereby resistance genes move from one bacterium to another. Staph bacteria also can exchange virulence genes using the same mechanism, but this was previously assumed to occur separately from the transfer of antibiotic resistance. According to a study published online (31 July 2009) in PLoS Pathogens, a study investigating Staphylococcus bacteria, including methicillin-resistant S. aureus (MRSA), discovered a potent staph toxin responsible for disease severity. The study also found the gene for the toxin traveling with a genetic component of Staphylococcus that controls resistance to antibiotics. The research involved more than 100 strains of S. aureus and S. epidermidis, both bacteria found on the skin of most people. In recent decades, these bacteria have become increasingly virulent, often causing severe disease that can be resistant to traditional antibiotics such as methicillin. In 2007, it was found that staphylococci secrete toxins of the phenol-soluble modulin (PSM) family that are primarily responsible for attracting and killing human white blood cells called neutrophils. This process is critical for the ability of S. aureus-including community-acquired MRSA-to cause disease. While screening S. aureus and S. epidermidis strains, the research team noticed that some strains produced one additional, previously unknown PSM toxin. The researchers hypothesized that the toxin was somehow connected to drug resistance. This idea surfaced because the toxin appeared in 10% of all MRSA strains and 68% of all methicillin-resistant S. epidermidis strains analyzed-whereas it was not found in strains of S. aureus or S. epidermidis that were sensitive to methicillin. The study confirmed its theory by identifying the specific location that encodes the toxin, which was in gene clusters that control drug resistance, known as SCCmec. The group named the new toxin PSM-mec. According to the authors, this work represents a previously unknown example of a toxin hitchhiking on staphylococcal mobile genetic elements that are primarily in charge of transferring antibiotic resistance. The finding should alert the research community that aggressive, drug-resistant staph can evolve more quickly than was assumed.” The research group is continuing its study of PSM-mec in S. epidermidis, where the toxin is more prevalent. Ultimately, being able to neutralize PSM-mec and other toxins that attack human defenses could lead to new treatments for S. aureus and S. epidermidis disease.

Prenatal Stress and Cerebral Palsy: A Nationwide Cohort Study in Denmark

Exposure to prenatal stress may affect neurodevelopment of the fetus, but whether this exposure increases the risk of cerebral palsy (CP) later in life is unknown. As a result, a study published in Psychosomatic Medicine (2009;71:615-618), was performed to examine the association between maternal bereavement during the prenatal time period and CP in childhood. The investigation was a nationwide cohort study of all 1,501,894 singletons born in Denmark from 1979 to 2004. By 2006, 39,601 children were identified whose mothers lost a close relative (child, spouse, parent, sibling) during pregnancy or up to 1 year before pregnancy; this cohort was classified as the exposed group. The outcome of interest was the diagnosis of CP as registered in the National Hospital Register. Results showed that exposure to maternal bereavement after the loss of a child during the prenatal period was associated with an increased risk of CP among children born preterm without intrauterine growth retardation (HR 2.26) and among children born at term with intrauterine growth retardation (HR 2.01). However, prenatal stress after maternal bereavement by loss of other relatives was not associated with an increased risk of CP. The authors concluded that the data suggest that extremely severe stress in prenatal life could increase the susceptibility for CP among children born preterm or with impaired fetal growth.

Does Anxiety Affect Risk of Dementia?

According to an article published in Psychosomatic Medicine (2009;71:659-666), a study was performed to examine the association of anxiety with incident dementia and cognitive impairment not dementia (CIND). The investigation was a prospective 17 year study of 1481 men who at ages 48 to 67 years had a baseline anxiety assessment. Trait Anxiety was assessed using the Spielberger State Trait Anxiety Inventory and psychological distress was assessed using the 30-item general health questionnaire. Cognitive screening was followed by a clinical examination. Medical notes and death certificates of those not seen were also examined. Outcomes were CIND and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) dementia. Results showed that of 1160 men who were cognitively screened, there were 174 cases of CIND and 69 cases of dementia. A further 21 cases of dementia were identified from medical records. After adjustment for age, vascular risk factors and premorbid cognitive function associations with higher anxiety (31st-95th centile) were for CIND odds ratio (OR) 2.31 and for dementia OR 2.37. These associations were slightly stronger for nonvascular (OR = 2.45) than for vascular impairment (OR = 1.94). Analyses of change in cognitive performance, assessed by the Cambridge Cognitive Examination of the Elderly subscales found some evidence for decline in learning memory with higher anxiety score (bage adj = -0.291), but not for any other subscale. According to the authors, anxiety is a risk factor for CIND and dementia, but the extent to which the association is independent of depression and whether or not it is causal requires further study.

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.

FDA Clears a Test for Ovarian Cancer 

The American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncologists published recommendations in 2002 for the role of generalist obstetrician-gynecologists in the early detection of ovarian cancer, which included a recommendation of patient referral to a gynecological oncologist when specific indicators of malignancy are present. These recommendations and later reports indicate that patients with ovarian cancer have improved survival when the surgery is performed by gynecologic oncologists as opposed to general gynecologists or surgeons. The FDA has cleared a test that can help detect ovarian cancer in a pelvic mass that is already known to require surgery. The test, called OVA1, helps patients and health care professionals decide what type of surgery should be done and by whom. OVA1 can identify women who may benefit from referral to a gynecological oncologist for their surgery, despite negative results from other clinical and radiographic tests for ovarian cancer. If other test results suggest cancer, referral to an oncologist is appropriate even with a negative OVA1 result. OVA1 should be used by primary care physicians or gynecologists as an adjunctive test to complement, not replace, other diagnostic and clinical procedures. OVA1 uses a blood sample to test for levels of five proteins that change due to ovarian cancer. The test combines the five separate results into a single numerical score between 0 and 10 to indicate the likelihood that the pelvic mass is benign or malignant. OVA1 is intended only for women, 18 years and older, who are already selected for surgery because of their pelvic mass. It is not intended for ovarian cancer screening or for a definitive diagnosis of ovarian cancer. Interpreting the test result requires knowledge of whether the woman is pre- or post-menopausal. For the approval, FDA reviewed a study of 516 patients, including 269 evaluated by non-gynecological oncologists, which compared OVA1 results with biopsy results. When combined with pre-surgical information, such as radiography and other laboratory tests, results from the OVA1 tests identified additional patients who might benefit from oncology referral who were not identified using pre-surgical information alone. OVA1 is developed by Vermillion Inc., headquartered in Fremont, Calif., in conjunction with researchers at The Johns Hopkins University in Baltimore. 

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

Target Health (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND (eCTD), IDE, NDA (eCTD), BLA (eCTD), PMA (eCopy) and 510(k) submissions, Management of Clinical Trials, Biostatistics, Data Management, EDC utilizing Target e*CRF®, Project Management, and Medical Writing. Target Health has developed a full suite of eClinical Trial software including 1) Target e*CRF® (EDC plus randomization and batch edit checks), 2) Target e*CTMSTM, 3) Target Document®, 4) Target Encoder®, 5) Target Newsletter®, 6) Target e*CTRTM (electronic medical record for clinical trials). Target Health ‘s Pharmaceutical Advisory Dream Team assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.