6 April 2008
I. WHAT'S NEW?
Target Health Is Looking For A Few Good People
II. QUIZ - (Fill In The Blanks)
Could Humans Live Forever Like Turritopsis Nutricula?
III. HISTORY OF MEDICINE
Dr. Leo Sternbach (1908-2005)
IV. PSYCHIATRY
Rates Of Rare Mutations Higher In Schizophrenia
V. OPHTHALMOLOGY
Older Corneas Suitable For Transplantation
VI. CARDIOLOGY
Zetia Plus Zocor (Vytorin) vs. Zocor Plus Placebo On Intima Thickening
VII.
REGULATORY AFFAIRS
FDA Approves Rotovirus Vaccine
VIII. TARGET HEALTH
Target Health Is Looking For A Few Good People
As Target Health has expanded to a second floor at 261 Madison Avenue. we are looking for a Director of Clinical Research (PhD preferred) and a really few smart CRAs who can integrate monitoring with Target e*CRF. A plus would be both Pharma and CRO experience. You would be working in a fast, no-nonsense and highly stimulating environment. We were directly involved with 4 regulatory submissions last year (1 already approved) and 1 regulatory submission already in 2008 (US and Europe). A 2nd submission will be made in Europe this quarter (47 centers, >1,600 subjects).Could Humans Live Forever Like Turritopsis Nutricula?
The Phylum Cnidaria contains species with highly regenerative reproductive potential. A number of cnidarians, including such diverse forms as jellyfish, 1) ___, sea anemones, and corals, can undergo ontogeny reversal, or reverse development, where one or more stages in the life 2) ___ can reactivate genetic programs specific to earlier stages, leading to back-transformation and morph rejuvenation. The switch is achieved by a variable combination of cellular processes, such as transdifferentiation, programmed cell death, and proliferation of interstitial 3) ___. The potential for ontogeny reversal, at this time, has limited ecological meaning and is probably just an extreme example of a more general strategy for withstanding unfavorable periods and allowing temporal persistence of species in the environment, in other words, for 4) ___. Turritopsis nutricula is a hydrozoan (jellyfish) with a life cycle in which the organisms develop through a series of stages leading to mature adults. However, this animal has the ability to revert back to the polyp stage after becoming mature. It is the first case in which a metazoan (animal) is capable of reverting completely to an immature, colonial stage after having reached maturity as a solitary stage. It does this through the cell development process of 5) ___. This cycle then repeats, rendering it effectively immortal. Ontogeny reversal is possible, but it does not occur typically after the onset of reproductive maturity. All stages of the medusa Turritopsis nutricula, from newly liberated to fully mature individuals, can transform back into colonial hydroids, either directly or through a resting period, thus escaping death and achieving potential 6) ___. This is the first metazoan known to revert to a colonial, juvenile morph after having achieved maturity in a solitary stage. Selective excision experiments show that the transformation of medusae into polyps occurs only if differentiated cells of the exumbrellar epidermis and part of the gastrovascular system are present, revealing a transformation potential unparalleled in the animal kingdom. What if we could transfer these “ontogeny reversal” gene(s) to humans? At the end of Arthur C. Clarke’s epic film, 2001: A Space Odyssey, an old man slowly reverses his life until he becomes a fetus, floating in embryonic fluid, about to be reborn. Could it be that Arthur C. Clarke was futuristically thinking of the human ability to switch on the transdifferentiation process?IV. PSYCHIATRY
Rates Of Rare Mutations Higher In Schizophrenia
The
prevailing genetic model of schizophrenia implicates common variants of
certain suspect candidate genes, each exerting modest effects, in
interaction with each other and environmental factors. This hypothesis
holds that risk stems from common variations in the sequence of the
genetic code that result in altered protein products. About a year ago,
Sebat, King and colleagues
reported evidence strengthening the case for a different kind of
genetic risk. Many people with autism were found to have different,
spontaneous and individually rare structural variations -- variations
in the number of copies of genes. These
copy number variations were scattered throughout the genome, suggesting
many different genes could be involved in autism spectrum disorders.
According to an article published online in "Science Express", March
27, 2008 (Science DOI: 10.1126/science.1155174), people with schizophrenia have
higher rates of rare genetic deletions and duplications that likely
disrupt the developing brain. These tiny anomalies were found in 15% of
adult onset schizophrenia patients and 20% of child and adolescent
onset patients, compared with only 5% of healthy participants.
Collectively, the mutations carried by patients were significantly more
likely than those in healthy participants to disrupt genes involved in
brain development, thus potentially implicating hundreds of genes in
the illness. The new findings in schizophrenia echo those in autism,
but also broaden their implications. The results suggest a new approach
for discovering genes for schizophrenia and other mental
disorders. Any mutation in the hundreds of genes involved in
brain development could lead to a different set of neurodevelopmental
consequences -- schizophrenia, autism, mental retardation, or no
illness at all. Each person with one of the illnesses could have a
different genetic cause for the disorder. The functional consequences
of these structural genetic variations may differ, depending on
interactions with other genes or environmental events making any gene
harboring a deleterious structural mutation a "candidate gene." Any
gene harboring one mutation likely contains others. Although each might
be individually rare, together such disease-causing variations in one
gene could explain a substantial number of illness cases, they suggest.
Among key study findings:
V. OPHTHALMOLOGY
Older Corneas Suitable For Transplantation
The cornea, a clear dome-shaped surface that covers the front of the eye, offers protection and helps focus light entering the eye. The availability of donor corneas has been adequate for the past 10 years in the US, where more than 33,000 corneal transplants are performed each year. However, recent changes in FDA regulations will likely cause a decrease in the supply of donated corneas. These new regulations, that took effect in June 2007, require additional screening and testing of potential donors for contagious diseases, registration of eye banks, more detailed records and labels, and stricter quarantine procedures. According to an article published in the journal Ophthalmology (2008;115:620-626), the age pool of corneas for transplant can be expanded to include donors up to 75 years of age. Study results showed that corneal transplants using tissue from older donors have similar rates of survival to those using tissue from younger donors. The five-year transplant success rate was the same -- 86% -- for transplants performed with corneas from donors ages 12 to 65 years and from donors ages 66 to 75. This is an important finding as many eye banks previously set the age limit for donors at 65 years or younger because some surgeons have been reluctant to use older corneas. According to the authors, the study results could expand the cormea donor pool by as much as 20% to 35%. The Cornea Donor Study (CDS), which was coordinated by the Jaeb Center for Health Research in Tampa, Fla., was a prospective cohort study conducted with 1,101 participants enrolled by 105 surgeons at 80 sites across the US. A prospective cohort study is one in which health outcomes in a group of participants are monitored over the duration of the study. Participants were between 40 and 80 years of age and were chosen for the study if they were in need of a corneal transplant for a corneal disease that put them at moderate risk for clouding of the transplanted cornea. Donor corneas were provided by 43 participating eye banks. All donor corneas met the Eye Bank Association of America's standards for human corneal transplantation and were consistent with eye banks' tissue ratings of good to excellent quality. After the transplant surgery, the participants were followed for five years. The transplant was considered a failure if a repeat corneal transplant was required or if the cornea was cloudy for at least three months. In a secondary study, the fate of the corneas' endothelial cells was examined. Endothelial cells are flat cells that live on the back of transplanted corneas and are essential for keeping the cornea clear. According to the authors, while there was cell loss in both age groups, in 86% of the cases the corneas remained clear after five years. The authors added that these findings suggest the opportunity for further research to continue to perfect corneal transplants. The CDS is the largest study of its type on corneal transplantation ever done. Its size and five-year patient follow-up, along with a simple trial design, have provided clear and important insights into contemporary transplantation.VI. CARDIOLOGY
Zetia Plus Zocor (Vytorin) vs. Zocor Plus Placebo On Intima Thickening
Ezetimibe (Zetia, Schering Plough), a cholesterol-absorption inhibitor, reduces levels of low-density lipoprotein (LDL) cholesterol when added to statin treatment. However, the effect of ezetimibe on the progression of atherosclerosis remains unknown. As a result, a double-blind, randomized, 24-month trial, published in the New England Journal of Medicine (2008; 358:1431-1443), was conducted to compare the effects of daily therapy with 80 mg of simvastatin (Zocor, Merck) either with placebo or with 10 mg of ezetimibe. The study was conducted in 720 patients with familial hypercholesterolemia. Patients underwent B-mode ultrasonography to assess the intima–media thickness of the walls of the carotid and femoral arteries. The primary outcome measure was the change in the mean carotid-artery intima–media thickness, which was defined as the average of the means of the far-wall intima–media thickness of the right and left common carotid arteries, carotid bulbs, and internal carotid arteries. The primary outcome, the mean change in the carotid-artery intima–media thickness, was 0.0058 mm in the simvastatin-only group and 0.0111 mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P=0.29). Secondary outcomes (consisting of other variables regarding the intima–media thickness of the carotid and femoral arteries) did not differ significantly between the two groups. At the end of the study, the mean LDL cholesterol level was 192.7 mg per deciliter in the simvastatin group and 141.3 mg per deciliter in the combined-therapy group (P<0.01). The differences between the two groups in reductions in levels of triglycerides and C-reactive protein were 6.6% and 25.7%, respectively, with greater reductions in the combined-therapy group (P<0.01 for both comparisons). Side-effect and safety profiles were similar in the two groups. It was concluded that in patients with familial hypercholesterolemia, combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima–media thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein. At this point the clinical significance of these findings is not known.VII. REGULATORY AFFAIRS
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 Approves Rotovirus Vaccine
Although the disease is usually self-limiting, rotavirus causes about 2.7 million cases of gastroenteritis in US children each year—about 55,000 to 70,000 of those require hospitalization; and between 20 and 60 deaths are attributed to it. Without vaccination, nearly every child in the US would likely be infected at least once with rotavirus by age 5. The FDA announced the approval of Rotarix, the second oral U.S. licensed vaccine for the prevention of rotavirus, an infection that causes gastroenteritis (vomiting and diarrhea) in infants and children. Rotarix is a liquid and given in a two-dose series to infants from 6 to 24 weeks of age. While there are many different strains of rotavirus, the vaccine protects against rotavirus gastroenteritis caused by the G1, G3, G4, and G9 strains. During studies involving more than 24,000 infants, Rotarix was effective in preventing both severe and mild cases of rotavirus-caused gastroenteritis during the first two years of life. The most common adverse reactions reported during clinical trials were fussiness, irritability, cough, runny nose, fever, loss of appetite and vomiting. In 1999, a different rotavirus vaccine from another manufacturer was voluntarily withdrawn from the U.S. market because of an association with an increased risk of intussusception, or intestinal folding, which can lead to potentially life-threatening intestinal blockage. Intussusception can occur in children spontaneously in the absence of vaccination, but to help ensure that Rotarix does not increase the risk of intussusception, its manufacturer conducted a study of more than 63,000 infants. In that study, there was no increase in the risk of intussusception in those who received Rotarix (31,673 infants) compared to those who received placebo (31,552 infants). Increased rates of convulsion and pneumonia-related deaths were observed in the Rotarix recipients in the intussusception study, however these events were not observed in other studies conducted by the manufacturer. Although the FDA has concluded that the available data do not establish that these events are related to the vaccine, the agency has requested the manufacturer to conduct post-marketing safety studies involving more than 40,000 infants to provide additional safety information. Rotarix is manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium.VIII. TARGET HEALTH
TARGET HEALTH INC. (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, IDE, NDA, PMA and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, Web Trials, utilizing Target e*CRF®, our proprietary Internet-based Clinical Trial System, and Medical Writing. 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.TARGET
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Ms Joyce Hays,
CEO
