Target Health Attending DIA Conference on Rare Diseases and Orphan Products


Warren Pearlson, Director of Business Development, will be attending DIA’s US Conference on Rare Diseases and Orphan Products which is being heldOctober 11-13, 2011at the Omni Shoreham Hotel inWashington,DC. Please let us know if you will be attending and stop by our booth and say hello.  Additional information can be found at:


Target Health has obtained the following Orphan Drug Designation for its clients:


1.   Alagille Syndrome

2.   Caries prevention, head and neck cancer

3.   Cushing’s syndrome secondary to ectopic ACTH secretion

4.   Edema-related effects in hospitalized patients with 3rd degree burns

5.   Gaucher Disease

6.   Hereditary angioedema

7.   Hospitalized patients with 3rd degree burns

8.   Osteonecrosis of the jaw

9.   Prevention of burn injury progression of acute, deep dermal burns in hospitalized patients

10. Scleroderma


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at


BioMedical Engineering

Electricity from the Nose: Making Power from Human Respiration


Graduate Student Jian Shi and Materials Science and Engineering Assistant Professor
Xudong Wang demonstrate a material that could be used to capture energy from respiration.



The same piezoelectric effect that ignites your gas stove top, with the push of a button could one day power sensors in your body via the respiration in your 1) ___. Writing in the September issue of the journal Energy and Environmental Science, Materials Science and Engineering Assistant Professor Xudong Wang, postdoctoral Researcher Chengliang Sun and graduate student Jian Shi (U of Wisconsin College of Engineering) report creating a plastic microbelt that vibrates when passed by low-speed airflow such as human 2) ___.

In certain materials, such as the polyvinylidene fluoride (PVDF) used by Wang’s team, an electric charge accumulates in response to applied mechanical stress. This is known as the piezoelectric effect. The researchers engineered PVDF to generate sufficient 3) ___ energy from respiration to operate small electronic devices. “Basically, we are harvesting mechanical energy from biological systems. The airflow of normal human respiration is typically below about two meters per second,“ says Wang. “We calculated that if we could make this material thin enough, small vibrations could produce a microwatt of electrical energy that could be useful for sensors or other devices implanted in the 4) ___.“


Researchers are taking advantage of advances in nanotechnology and miniaturized electronics to develop a host of biomedical devices that could monitor blood 5) ___ for diabetics or keep a pacemaker battery charged so that it would not need replacing. What’s needed to run these tiny devices is a miniscule power supply. Waste energy in the form of blood flow, motion, heat, or in this case respiration, offers a consistent source of 6) ___. Wang’s team used an ion-etching process to carefully thin material while preserving its piezoelectric properties. With improvements, he believes the thickness can be controlled down to the submicron level. Because PVDF is biocompatible, he says the development represents a significant advance toward creating a practical micro-scale device for harvesting 7) ___from respiration.


ANSWERS: 1) nose; 2) respiration; 3) electrical; 4) face; 5) glucose; 6)power; 7) energy

Nobel Medicine Winner Ralph Steinman’s Last Big Experiment: Himself


Nobel prize for medicine winner, Canadian-born Ralph Steinman MD. Rockefeller University/Handout




Dr. Ralph Steinman helped to create experiments to save his own life, as he waged a very personal battle with pancreatic cancer. The winner of the 2011 Nobel prize in medicine, who died only three days before the award was announced on October 3rd, ultimately tried as many as eight unproven treatments. Friends and colleagues said Steinman was devoted to research that would make a difference in the lives of people.


Ralph Marvin Steinman was a Canadian immunologist and cell biologist who in 1973 coined the term dendritic cells while working as a postdoc in the lab of Zanvil A. Cohn, also at Rockefeller University.  He graduated from McGill University and Harvard Medical School. Steinman spent his entire career on immunology research for which he won the Nobel Prize, an honor he shares with American Bruce Beutler and French biologist Jules Hoffmann for their contributions to explaining the immune system. Steinman’s discovery of dendritic cells in 1973 led to the first therapeutic cancer vaccine, Dendreon’s Provenge, which treats men with advanced prostate cancer.


When Steinman was diagnosed with stage-four pancreatic cancer four and-a-half years ago, the cancer had already begun to spread to his lymph nodes. He elected to receive all of the conventional therapy that was available. He had surgery and conventional chemotherapy as well, but he was quite certain that was unlikely to cure him or even allow him very much time. Dr. Michel Nussenzweig, head of molecular immunology at Rockefeller who had worked with Steinman for more than three decades, said Steinman had already been working on dendritic cell therapy when he became ill and wanted to try it himself. The medical community rallied around.


The Food and Drug Administration regulators were quick and responsive, but did not cut the team any slack. However, things that would have taken months to turn around, turned around in days. Nussenzweig took a portion of Steinman’s tumor and used that to grow cells in the lab that would help form the basis of personalized cancer treatments. Steinman initially got an experimental vaccine called GVAX, which was first developed by Dr. Elizabeth Jaffee at Johns Hopkins University in Baltimore and is now being developed by BioSante Pharmaceuticals. The first set of dendritic cells he received, were given to him in collaboration with a biotech company called Argos Therapeutics. The researchers made dendritic cells from Steinman’s blood and from blood precursor cells. He got them eight or nine times over a course of several months, and then also received chemotherapy.


Researchers at Baylor University Medical Center in Dallas also offered a melanoma vaccine they were working on for Steinman to try. And then there were more conventional treatments: he got a chemotherapy drug from Eli Lilly and Co called gemcitabine or Gemzar, Bristol-Myers Squibb Co’s newly approved melanoma treatment ipilimumab or Yervoy, Roche’s Tarceva, which targets proteins involved in cancer growth, and a drug from Roche’s Genentech unit that interferes with the so-called hedgehog signaling pathway that can become reactivated with certain cancers. And yes, all of the treatments had been cleared for use by U.S. regulators in clinical trials.


Steinman lived four-and-a-half years after getting a diagnosis that typically kills people within a year or less. Colleagues say it is impossible to know what prolonged his life. Whether it was surgery, chemotherapy or the experimental treatments, Steinman was convinced it was his own beloved dendritic cells, the specialized immune system that eventually won him the Nobel Prize. He worked up to the very end.


Nobel awards are not given to people posthumously and earlier in the week Steinman’s daughter Alexis even joked with her father that he needed to hold out until the awards were announced on Monday. In the end, the Nobel Committee decided to award the prize to Steinman posthumously.

Missing Clue in Vertebrate Evolution:

Are Humans Just Modified Fish?



Pectoral fin muscle formation in paddlefish (Polyodon spathula) utilizes the fully derived mode of appendicular muscle formation and is not associated with an epithelial extension. (Credit: Cole et al., PLoS Biology, DOI: 10.1371/journal.pbio.1001168)



A study into the muscle development of several different fish has given insights into the genetic leap that set the scene for the evolution of hind legs in terrestrial animals. This innovation gave rise to the tetrapods – four-legged creatures, and our distant ancestors – that made the first small steps on land some 400 million years ago. A team of Australian scientists led by Professor Peter Currie, of the Australian Regenerative Medicine Institute at Monash University, and Dr Nicolas Cole, of the University of Sydney, report their results October 4 in online, open access journal PLoS Biology.


Scientists have long known that ancient lungfish species are the ancestors of the tetrapods. These fish could survive on land, breathing air and using their pelvic fins to propel themselves. Australia is home to three species of the few remaining lungfish — two marine species and one inhabiting Queensland’s Mary River basin. There are big gaps in our knowledge, however. Most conclusions have previously been drawn from fossil skeletons, but the muscles critical to locomotion cannot be preserved in the fossil record.


The team used fish living today to trace the evolution of pelvic fin muscles to find out how the load-bearing hind limbs of the tetrapods evolved. They compared embryos of the descendants of species representing key turning points in vertebrate evolution to see if there were differences in pelvic fin muscle formation. They studied “primitive” cartilaginous fish – Australia’s bamboo shark and its cousin, the elephant shark – as well as three bony fishes – the Australian lungfish, the zebrafish and the American paddlefish. The bony fish and in particular the lungfish are the closest living relative of the tetrapods’ most recent common ancestor with fish.


“We examined the way the different fish species generated the muscles of their pelvic fins, which are the evolutionary forerunners of the hind limbs,” said Professor Currie, a developmental biologist. Currie and his team genetically engineered the fish to trace the migration of precursor muscle cells in early developmental stages as the animal’s body took shape. These cells in the engineered fish were made to emit a red or green light, allowing the team to track the development of specific muscle groups. They found that the bony fish had a different mechanism of pelvic fin muscle formation from that of the cartilaginous fish, a mechanism that was a stepping stone to the evolution of tetrapod physiology.


“Humans are just modified fish,” said Professor Currie. “The genome of fish is not vastly different from our own. We have shown that the mechanism of pelvic muscle formation in bony fish is transitional between that in sharks and in our tetrapod ancestors.”

Priming With DNA Vaccine Makes Avian Flu Vaccine Work Better



Since 2003, there have been 564 confirmed cases of human H5N1 influenza infection and 330 associated deaths worldwide, according to the most recent figures from the World Health Organization. Developing an effective vaccine against H5N1 influenza has proved difficult, because vaccines containing the whole, inactivated virus often fail to generate high levels of protective antibodies in people. The VRC studies confirm that volunteers who received only two doses of an inactivated H5N1 virus vaccine spaced 24 weeks apart produced only modest levels of H5N1-directed antibodies.


According to an article published online in The Lancet Infectious Diseases (4 October 2011), the immune response to an H5N1 avian influenza vaccine was greatly enhanced in healthy adults if they were first primed with a DNA vaccine expressing a gene for a key H5N1 protein. Results showed that a majority of study volunteers who received the DNA vaccine 24 weeks before receiving a booster vaccine made from whole, inactivated H5N1 virus produced high levels of antibodies thought to be protective against the globular head region of a protein called hemagglutinin (HA). Traditional seasonal influenza vaccines are designed to elicit antibodies to the head region of HA, but it changes each year and so vaccines must be repeated annually to maintain immunity. In some volunteers, the prime-boost vaccine regimen also spurred production of broadly neutralizing antibodies aimed at the HA stem, a region that is relatively constant across many strains of influenza viruses.


In 2010, the NIH’s NIAID Vaccine Research Center (VRC) studies in mice, ferrets and monkeys showed that a DNA prime-boost influenza vaccine regimen can elicit broadly neutralizing antibodies directed against the HA stem. The VRC study team is hoping to apply this approach to research on vaccines against other seasonal and pandemic influenza strains too.


Of the 26 volunteers who received the vaccines 24 weeks apart, 21 produced antibodies at levels predicted to protect them from H5N1 influenza. The antibody levels in that group were more than four times higher than those seen in volunteers who received two doses of inactivated H5N1 virus vaccine. Among volunteers who received their booster vaccine just four weeks after the DNA prime, only 4 out of 15 produced protective levels of antibodies. In both clinical studies, the H5N1 DNA priming vaccine was found to be safe. That finding is consistent with data from previous clinical trials in which VRC DNA vaccines for HIV, Ebola,Marburg,West Nilevirus, SARS and seasonal influenza have been tested and found to be safe in a total of 2,100 volunteers.


Next, the team will try to improve its DNA and other gene-based vaccines to more readily elicit antibodies directed at the stem region of the HA protein. The VRC group also is planning a larger trial of a prime-boost vaccine for seasonal influenza.

Undiagnosed Diseases Program Documents 2-Year Pilot as Clinic of Last Resort



After its first two years on the job, the Undiagnosed Diseases Program (UDP) of the National Institutes of Health (NIH) is citing successes in patients whose cases have stumped specialists at leading medical institutions around the country. The program’s first retrospective analysis was published in the early online issue of Genetics in Medicine (26 September 2011). The successes include the diagnoses of siblings whose calcium-riddled blood vessels made it excruciatingly painful to walk, a woman with life-threatening protein deposits in her muscles and a 20-year-old whose diagnosis makes him the oldest survivor of his previously undiagnosed muscle and lung disorder. The UDP is supported by the NIH Office of the Director, NHGRI, the NIH Office of Rare Diseases Research (ORDR) and theNIHClinicalCenter.


The report focuses on 160 patients of the total 326 cases accepted into the program. More than half of the accepted patients had undiagnosed neurological problems. Other prominent disorder categories include gastrointestinal disease; fibromyalgia and chronic fatigue syndrome; immune-mediated and rheumatic illnesses; psychiatric conditions; pain; dermatologic disorders; and cardiovascular disease.


So far, most of the solved cases – 37 of 39 cases for which the UDP team arrived at a diagnosis – involved diseases previously encountered in the world of medicine, according to UDP authors. In general, about 500 diseases are common enough to be in any physician’s repertoire for diagnosis, while another 6,500 are known but are exceptionally rare, according to ORDR data.


UDP researchers reviewed, evaluated and diagnosed 23 patients with rare diseases, of which 15 cases reflect extremely rare diseases affecting fewer than 10,000 people. The authors note that while these are known disorders, some lack diagnostic tests or medical definitions to describe them. Rare diseases are defined as those affecting fewer than 200,000 people in theUnited States. The program has also delved into the realm of unknown maladies.


In February, the UDP announced the program’s first discovery of a new disease, called ACDC, or arterial calcification due to deficiency of CD73, in the New England Journal of Medicine. CD73 is a protein that produces a small molecule, adenosine, which protects arteries from calcifying. The siblings whose cases led to discovery of ACDC continue to experience pain while walking more than a short distance. However, the NIH team has obtained approval to start a drug treatment protocol which will be initiated within months that could improve the condition.


The patient who UDP researchers encountered with an unexplained muscle condition was diagnosed with a rare form of amyloidosis, a condition in which bone marrow produces excess immunoglobulin proteins, which had accumulated in the patient’s muscle tissue. The NIH team referred the patient for a stem-cell, bone marrow transplant, using healthy donor stem cells. The patient has subsequently experienced progressive improvement in her condition. The UDP team also succeeded in diagnosing the 20-year-old patient with a condition called spinal muscular atrophy with respiratory distress. The condition causes damage to muscles, including respiratory muscles. The patient remains dependent on a respirator for much of his day but last year achieved the significant personal milestone of high school graduation. The diagnosis has allayed the patient’s concern that the condition might at any point impair his learning.


A typical UDP patient visits theNIHClinicalCenterfor one week. The case is evaluated by specialists from several of NIH’s 27 institutes and centers, with expertise in areas such as neurology, radiology, dentistry and rheumatology. A key component of the program is genetics, so researchers collect DNA from blood or tissue samples from all participating patients, and often from family members to support the genomic analyses. Most of the patients accepted in the first two years of the UDP had their DNA analyzed for known single nucleotide polymorphisms (SNPs), which reflect differences in the single chemical subunits of DNA that could indicate a genetic disorder. Their tool in the SNP analysis process is called a million-SNP array, which can be used to find potentially important differences between the genome of an affected individual and an unaffected family member, pointing to the genetic cause of a disorder. This approach has resulted in three successful diagnoses.


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US Task Force Recommends Against Routine PSA Testing



One in six men in the US will eventually be found to have prostate cancer, making it the second most common form of cancer in men after skin cancer. An estimated 32,050 men died of prostate cancer last year and 217,730 men received the diagnosis. The disease is rare before age 50, and most deaths occur after age 75.


The P.S.A. test measures a protein – prostate-specific antigen – that is released by prostate cells, and there is little doubt that it helps identify the presence of cancerous cells in the prostate. But a vast majority of men with such cells never suffer ill effects because their cancer is usually slow-growing.


According to a key government health panel, healthy men should no longer receive a P.S.A. blood test to screen for prostate cancer because the test does not save lives overall and often leads to more tests and treatments that needlessly cause pain, impotence and incontinence in many. The draft recommendation, by the United States Preventive Services Task Force and due for official release next week, is based on the results of five well-controlled clinical trials and could substantially change the care given to men 50 and older. According to the report, there are 44 million such men in theUS, and 33 million of them have already had a P.S.A. test – sometimes without their knowledge – during routine physicals.


As the P.S.A. test has grown in popularity, the devastating consequences of the biopsies and treatments that often flow from the test have become increasingly apparent. From 1986 through 2005, one million men received surgery, radiation therapy or both who would not have been treated without a P.S.A. test, according to the task force. Among them, at least 5,000 died soon after surgery and 10,000 to 70,000 suffered serious complications. Half had persistent blood in their semen, and 200,000 to 300,000 suffered impotence, incontinence or both. As a result of these complications, the man who developed the test, Dr. Richard J. Ablin, has called its widespread use a “public health disaster.”


According to the report, P.S.A. testing is most common in men over 70, where the benefit is the least as a result of surgery and radiation. Some doctors treat patients who have high P.S.A. levels with drugs that block male hormones, although there is no convincing evidence that these drugs are helpful in localized prostate cancer and they often result in impotence, breast enlargement and hot flashes.


Of the trials conducted to assess the value of P.S.A. testing, the two largest were conducted inEuropeand theUS. According to the task force’s draft recommendation statement, both trials “demonstrate that if any benefit does exist, it is very small after 10 years.”


The European trial had 182,000 men from seven countries who either got P.S.A. testing or did not. When measured across all of the men in the study, P.S.A. testing did not cut death rates in nine years of follow-up. But in men ages 55 to 69, there was a very slight improvement in mortality. The American trial, with 76,693 men, found that P.S.A. testing did not cut death rates after 10 years.


Dr. Eric Klein of the Cleveland Clinic, an expert in prostate cancer, said he disagreed with the task force’s recommendations. Citing the European trial, he said “I think there’s a substantial amount of evidence from randomized clinical trials that show that among younger men, under 65, screening saves lives.”


The task force’s recommendations apply only to healthy men without symptoms. The group did not consider whether the test is appropriate in men who already have suspicious symptoms or those who have already been treated for the disease. The recommendations will be open to public comment next week before they are finalized. Recommendations of the task force often determine whether federal health programs like Medicare and private health plans envisioned under the health reform law pay fully for a test. But legislation already requires Medicare to pay for P.S.A. testing no matter what the task force recommends.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.



FDA Approves Combination Therapy Juvisync (sitagliptin and simvastatin)



About 20 million people in theUShave type 2 diabetes, and they often have high cholesterol levels as well. These conditions can lead to increased risk of heart disease, stroke, kidney disease and blindness, among other chronic conditions, particularly if left untreated or poorly treated.


Sitagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor that enhances the body’s own ability to lower elevated blood sugar and is approved for use in combination with diet and exercise to improve glycemic control in adults with type 2 diabetes. Simvastatin is an HMG-CoA reductase inhibitor, or statin, approved for use with diet and exercise to reduce the amount of “bad cholesterol“ (low-density lipoprotein cholesterol or LDL-C) in the blood.


The FDA has approved Juvisync (sitagliptin and simvastatin), a fixed-dose combination (FDC) prescription medication that contains two previously approved medicines in one tablet for use in adults. This FDC is based on substantial experience with both sitagliptin and simvastatin, and the ability of the single tablet to deliver similar amounts of the drugs to the bloodstream as when sitagliptin and simvastatin are taken separately. Juvisync is a convenience combination and should only be prescribed when it is appropriate for a patient to be placed on both of these drugs.


Juvisync was approved in dosage strengths for sitagliptin/simvastatin of 100 mg/10 mg, 100 mg/20 mg and 100 mg/40 mg. The company has committed to develop FDC tablets with the sitagliptin 50 mg dose, as Juvisync 50 mg/10 mg, 50 mg/20 mg and 50 mg/40 mg. Pending availability of the FDC tablets containing 50 mg of sitagliptin, patients who require this dose should continue to use the single ingredient sitagliptin tablet. There is no plan to develop FDCs with the sitagliptin 25 mg dose as use of this dose is quite low.


Simvastatin is currently marketed in dosage strengths of 5, 10, 20, 40, and 80 mg. Due to recent restrictions placed on the use of the 80 mg dose because of a higher risk of muscle toxicity, there will not be a FDC using this dose. There is also no plan to develop FDCs with the simvastatin 5 mg dose as use of this dose is quite low as well.


The FDA has recently become aware of the potential for statins to increase blood sugar levels in patients with type 2 diabetes. This risk appears very small and is outweighed by the benefits of statins for reducing heart disease in diabetes. However, the prescribing information for Juvisync will inform doctors of this possible side effect. The company will also be required to conduct a post-marketing clinical trial comparing the glucose lowering ability of sitagliptin alone compared to sitagliptin given with simvastatin.


Juvisync is approved with a Medication Guide that provides important information to patients. The most common side effects of Juvisync include upper respiratory infection; stuffy or runny nose and sore throat; headache; muscle and stomach pain; constipation; and nausea.


Juvisync is manufactured by MSD International GmbH Clonmel, Co. inTipperary,Ireland.

Target Health ( a full service e*CRO, is committed to serve the pharmaceutical community through knowledge, experience, technology and connectivity. Target Health strives to optimize the life cycle of drugs, biologics and devices with expertise, leadership, innovation and teamwork. Target Health Inc. has fulltime staff dedicated to all aspects of Regulatory Affairs, Clinical Research, Biostatistics, Data Management, Strategic Planning and Drug and Device Development. Target Health is committed to the paperless clinical trial and has developed a full suite of eClinical Trial software including:


1) Target e*CRF® (EDC Made Simple)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

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6) Target e*Monitoring™

7) Target Newsletter®

8) Target e*CTR™ (eSource, electronic medical record for clinical trials).


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