Dave Luke, PharmD, FACA, FCCP, Joins Target Health as Sr. Director of Clinical and Scientific Affairs


As part of the continuing growth of Target Health Inc. we welcome Dave Luke, PharmD, FACA, FCCP, as Sr. Director of Clinical and Scientific Affairs. Dave will work closely with all departments at Target Health to provide both clinical, scientific and leadership support for all of our programs.


Prior to joining Target Health, Dave spent 20 years at Pfizer where he was Senior Medical Director, MSL in the areas of Infectious Diseases, Oncology, Immunology, Cardiology, Neurology, Pain; National Medical Council Coordinator, MSL; Faculty Member, Pfizer Research University; and Senior Associate Director, Clinical Research – Phase 3 Development. Prior to joining Pfizer, Dave was Director of the HIV Clinical Research, Clinical Pharmacology Unit at Hoffmann-La Roche Inc., and held academic positions at Rutgers, State University of New Jersey, University of Houston, and University of Texas M.D. Anderson Cancer Center, Houston, TX. Dave has a Doctor of Pharmacy degree from the University of the Sciences in Philadelphia (formerly known as the Philadelphia College of Pharmacy and Sciences).  Between 1997 and 2004 Dave was also a Member of the NASA/Johnson Space Center Steering Committee.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). 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, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.


Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor



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Homosexuality May Have Evolved in Humans Because It Helps Us Bond

Source: Public Domain, Wikipedia Commons



Homosexuality, or being gay is romantic attraction between members of the same gender. As such, being gay is “an enduring pattern of emotional, romantic, and/or attractions“ to people of the same 1) ___. It “also refers to a person’s sense of identity based on those attractions, related behaviors, and membership in a community of others who share those attractions.“ Along with bisexuality and heterosexuality, being gay is one of the three main categories within the heterosexual-homosexual continuum. The exact cause of being gay is not known, but it is believed to be caused by a complex interplay of genetic, hormonal, and environmental influences, and do not view it as a 2) ___. The favored biologically-based theories point to genetic factors, the early uterine environment, both, or the inclusion of genetic and social factors. There is no substantive evidence which suggests parenting or early 3) ___ experiences play a role when it comes to being gay. While some people believe that gay activity is unnatural, scientific research has shown that being gay could be a normal and natural variation in human 4) ___ and is not in and of itself a source of negative psychological effects.


The number of people who identify as gay or lesbian is difficult to estimate reliably for a variety of reasons, including many gay or lesbian people not openly identifying as such due. Homosexual behavior has also been documented and is observed in many non-human 5) ___ species. Many gay and lesbian people are in committed same-gender relationships, though only recently have census forms and political conditions facilitated their visibility and enumeration. These relationships are equivalent to heterosexual relationships in essential psychological respects.


Gay relationships and acts have been admired, as well as condemned, throughout recorded 6) ___, depending on the form they took and the culture in which they occurred. Since the end of the 19th century, there has been a global movement towards increased visibility, recognition, and legal rights for gay people, including the rights to marriage and civil unions, adoption and parenting, employment, military service, equal access to health care, and the introduction of anti-bullying legislation to protect gay minors.


Scientists have long been puzzled by homosexuality, as it seems to be at odds with the basic human drive to 7) ___. Various theories have been offered, from the notion that gay men make more diligent uncles than their heterosexual counterparts (and thus are better at ensuring the survival of their relatives) to the notion that the same gene that codes for homosexuality in men makes women more fertile. Now researchers from the University of Portsmouth in England have put forth a controversial new theory. They say homosexuality evolved in humans and other primates because it helps us form 8) ___ with one another. “From an evolutionary perspective, we tend to think of sexual behavior as a means to an end for reproduction,“ Dr. Diana Fleischman, an evolutionary psychologist at the university and one of the researchers, said in a written statement. “However, because sexual behavior is intimate and pleasurable, it is also used in many species, including non-human primates, to help form and maintain social bonds. We can all see this in romantic couples who bond by engaging in sexual behavior even when reproduction is not possible.“ For the study, 92 women were asked to indicate the extent to which they agreed or disagreed with various hypothetical statements about homosexual behavior, such as: “The idea of kissing a person of the same gender is sexually arousing to me“ and “If someone of the same gender made a pass at me I would be disgusted.“ Then the researchers measured levels of the hormone 9) ___ in the women’s saliva. Progesterone is linked to social bonding. What did the researchers find? Women with high progesterone levels were more open to engaging in homosexual activity. The researchers theorize that progesterone may make people want to bond with others, and since sexual activity is one form of bonding, homosexual as well as heterosexual behavior is encouraged. In another experiment, 59 men did word completion puzzles, filling in the blanks of words from one of the following three categories: friendship (for instance, “fr  ds“ becomes “friends“), or neutral (“sq.ar.“ becomes “square“). The researchers found that the men who completed the friendship puzzles were 26% more likely to be open to the idea of having relationships with other men compared to the men in the other two groups. In other words, when men were led to think about forming bonds with others, they were more open to homosexual as well as heterosexual behavior, Fleischman told The Huffington Post in an email. “It’s very complex, but it’s clear there’s a continuum between 10) ___ and sexuality, and the ability to engage sexually with those of the same gender or the opposite gender is common,“ Fleischman said in the statement. “In humans, much, if not most of same-gender behavior occurs in those who don’t identify as homosexual.“ An intriguing theory, for sure. But not everyone is buying the new research. “It is a plausible theory that there is a societal benefit from homosexual behavior, but the link to progesterone is probably spurious,“ Dr. Gerard Conway, professor of reproductive endocrinology at University College, London, who was not involved in the study, told reporters. “It’s a long way from proving cause and effect.“ The study was published November 25, 2016 in the journal Archives of Sexual Behavior. TED lecture: Homosexuality: It’s about survival| James O’Keefe MD


ANSWERS: 1) gender; 2) choice; 3) childhood; 4) behavior; 5) animal; 6) history; 7) reproduce; 8) bonds; 9) progesterone; 10) affection



Burning of two homosexuals at the stake outside Z?rich, 1482 (Spiezer Schilling).

Source: Public Domain, Wikipedia Commons



Classical period: Europe


The earliest Western documents (in the form of literary works, art objects, and mythographic materials) concerning same-gender relationships are derived from ancient Greece. With regard to male homosexuality such documents depict a world in which relationships with women and relationships with youths were the essential foundation of a normal man’s love life. Same-gender relationships were a social institution variously constructed over time and from one city to another. The formal practice, an erotic yet often restrained relationship between a free adult male and a free adolescent, was valued for its pedagogic benefits and as a means of population control, though occasionally blamed for causing disorder. Plato praised its benefits in his early writings but in his late works proposed its prohibition. Aristotle, in the Politics, dismissed Plato’s ideas about abolishing homosexuality; he explains that barbarians like the Celts accorded it a special honor, while the Cretans used it to regulate the population.


Little is known of female homosexuality in antiquity. Sappho, born on the island of Lesbos, was included by later Greeks in the canonical list of nine lyric poets. The adjectives deriving from her name and place of birth (Sapphic and Lesbian) came to be applied to female homosexuality beginning in the 19th century. Sappho’s poetry centers on passion and love for various personages and both genders. The narrators of many of her poems speak of infatuations and love (sometimes requited, sometimes not) for various females, but descriptions of physical acts between women are few and subject to debate.


Sappho reading to her companions on an Attic vase of c. 435 BCE.

Source: Public Domain, Wikipedia Commons



In Ancient Rome the young male body remained a focus, but relationships were between older free men and slaves or freed youths who took the receptive role. The Hellenophile emperor Hadrian is renowned for his relationship with Antinous, but the Christian emperor Theodosius I decreed a law on 6 August 390, condemning passive males to be burned at the stake. Justinian, towards the end of his reign, expanded the proscription to the active partner as well (in 558), warning that such conduct can lead to the destruction of cities through the “wrath of God“. Notwithstanding these regulations, taxes on brothels of boys available for homosexual relationships continued to be collected until the end of the reign of Anastasius I in 518.




During the Renaissance, wealthy cities in northern Italy – Florence and Venice in particular – were renowned for their widespread practice of same-gender love, engaged in by a considerable part of the male population and constructed along the classical pattern of Greece and Rome. But even as many of the male population were engaging in same-gender relationships, the authorities, under the aegis of the Officers of the Night court, were prosecuting, fining, and imprisoning a good portion of that population. From the second half of the 13th century, death was the punishment for male homosexuality in most of Europe. The relationships of socially prominent figures, such as King James I and the Duke of Buckingham, served to highlight the issue, including in anonymously authored street pamphlets: “The world is chang’d I know not how, For men Kiss Men, not Women now;.Of J. the First and Buckingham: He, true it is, his Wives Embraces fled, To slabber his lov’d Ganimede“ (Mundus Foppensis, or The Fop Display’d, 1691).


18th and 19th Centuries


Love Letters Between a Certain Late Nobleman and the Famous Mr. Wilson was published in 1723 in England and was presumed by some modern scholars to be a novel. The 1749 edition of John Cleland’s popular novel Fanny Hill includes a homosexual scene, but this was removed in its 1750 edition. Also in 1749, the earliest extended and serious defense of homosexuality in English, Ancient and Modern Pederasty Investigated and Exemplified, written by Thomas Cannon, was published, but was suppressed almost immediately. It includes the passage, “Unnatural Desire is a Contradiction in Terms; downright Nonsense. Desire is an amatory Impulse of the inmost human Parts.“ Around 1785 Jeremy Bentham wrote another defense, but this was not published until 1978. Executions for certain activities continued in the Netherlands until 1803, and in England until 1835. Between 1864 and 1880 Karl Heinrich Ulrichs published a series of twelve tracts, which he collectively titled Research on the Riddle of Man-Manly Love. In 1867, he became the first self-proclaimed gay person to speak out publicly in defense of gayness when he pleaded at the Congress of German Jurists in Munich for a resolution urging the repeal of discriminatory laws. A book by Havelock Ellis, published in 1896, challenged theories that homosexuality was abnormal, as well as stereotypes, and insisted on the ubiquity of homosexuality and its association with intellectual and artistic achievement. Although medical texts like these (written partly in Latin to obscure the graphic details) were not widely read by the general public, they did lead to the rise of Magnus Hirschfeld’s Scientific-Humanitarian Committee, which campaigned from 1897 to 1933 against discriminatory laws in Germany, as well as a much more informal, unpublicized movement among British intellectuals and writers, led by such figures as Edward Carpenter and John Addington Symonds. Beginning in 1894 with Homogenic Love, Socialist activist and poet Edward Carpenter wrote a string of pro-gay articles and pamphlets, and “came out“ in 1916 in his book My Days and Dreams. In 1900, Elisar von Kupffer published an anthology of homosexual literature from antiquity to his own time, Lieblingminne und Freundesliebe in der Weltliteratur.


Hearing Loss Prevalence Declining in Adults Aged 20-69


According to an article published in JAMA Otolaryngology – Head & Neck Surgery, (15 December 2016), hearing loss among U.S. adults aged 20 to 69 has declined over the last decade, even as the number of older Americans continues to grow. These findings, also confirm that hearing loss is strongly associated with age and other demographic factors such as gender, race/ethnicity, and education. Noise exposure, which is potentially preventable, was also significant but less strongly associated after adjustment for other factors..


For the study, hearing loss trends over time were examined in adults aged 20 to 69, by comparing hearing health data collected as part of the National Health and Nutrition Examination Survey (NHANES) over two time periods: 2011-2012 and 1999-2004. NHANES is a nationally representative health interview and examination survey of U.S. adults. NHANES participants listened to tones of various frequencies that were presented at different loudness levels. The study defined hearing loss as an average hearing threshold in at least one ear that was greater than 25 decibels in loudness (about as loud as rustling leaves). Data were also age- and gender-adjusted to reduce the effects of demographic differences across the two time periods.


Results showed that the overall annual prevalence of hearing loss dropped slightly, from 16% to 14%, or 28 million adults, in the 1999-2004 period versus 27.7 million in the 2011-2012 period. This decline in absolute numbers was observed despite an increase in the population generally, and in the relative number of adults aged 50 to 69 in the more recent time period. The new results are consistent with previous findings showing improvements in hearing over time, when researchers compared NHANES data from 1999 to 2004 with data from 1959 to 1962.


The authors were not able explain the reason why hearing loss prevalence is declining but speculate possible factors could include fewer manufacturing jobs, increased use of hearing protectors, less smoking, and advances in health including better medical care to manage risk factors associated with hearing loss. The study found that age was the strongest predictor of hearing loss, with the greatest amount of hearing loss in the oldest age group surveyed (aged 60 to 69). Across all ages, men were about twice as likely as women to have hearing loss. In addition, lower education level and heavy use of firearms were associated with hearing loss. Non-Hispanic white adults were more likely to have hearing loss than adults in other ethnic groups, with non-Hispanic black adults having the lowest risk. The study also found that age- and gender-adjusted hearing loss declined over the years for the averaged high frequencies (3-6 kilohertz) in both ears, and for speech frequencies (0.5-4 kilohertz) in one ear. People aged 70 and above, although not studied in this report, have the highest prevalence of hearing loss of any age group.



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Clinical Trial Demonstrates Shrinkage in Pediatric Neural Tumors


Neurofibromatosis type 1 (NF1), also called von Recklinghausen’s disease, is a rare genetic disorder characterized by the development of multiple noncancerous (benign) tumors of nerves and skin (neurofibromas) and areas of abnormally decreased or increased coloration (hypo- or hyperpigmentation) of the skin. Areas of abnormal pigmentation typically include pale tan or light brown discolorations (cafe-au-lait spots) on the skin of the trunk and other regions as well as freckling, particularly under the arms (axillary) and in the groin (inguinal) area. Such abnormalities of skin pigmentation are often evident by one year of age and tend to increase in size and number over time. At birth or early childhood, affected individuals may have relatively large benign tumors that consist of bundles of nerves (plexiform neurofibromas). Individuals with NF1 may also develop benign tumor-like nodules of the colored regions of the eyes (Lisch nodules) or tumors of the optic nerves (second cranial nerves), which transmit nerve impulses from the innermost, nerve-rich membrane of the eyes (retinas) to the brain. More rarely, affected individuals may develop certain malignant (cancerous) tumors. NF1 may also be characterized by unusual largeness of the head (macrocephaly) and relatively short stature. Additional abnormalities may also be present, such as episodes of uncontrolled electrical activity in the brain (seizures); learning disabilities; speech difficulties; abnormally increased activity (hyperactivity); and skeletal malformations, including progressive curvature of the spine (scoliosis), bowing of the lower legs, and improper development of certain bones. Plexiform neurofibromas develop in up to 50% of people with NF1. Complete surgical removal of the tumors is rarely feasible, and incompletely resected tumors tend to grow back.


The disease-causing gene for NF1 was first identified in 1990 by two independent teams, one of them led by NIH Director Francis S. Collins, Ph.D., M.D., who at the time was chief of Medical Genetics at the University of Michigan. The other team was led by Ray White at the University of Utah. Research to understand the gene’s function revealed that deregulation of the RAS signaling pathway was the most likely cause of tumor development. Numerous drugs that target RAS-related signaling pathways have been tested in patients with NF1 in phase I and phase II clinical trials, with disappointing results.


According to an article published online in the New England Journal of Medicine (29 Dec. 2016), in an early-phase clinical trial of a new oral drug, selumetinib, children with NF1 and plexiform neurofibromas, tumors of the peripheral nerves, tolerated selumetinib and, in most cases, responded to it with tumor shrinkage. NF1 affects 1 in 3,000 people.


The multicenter phase I clinical trial, which included 24 patients, and was conducted at the NIH Clinical Center and three participating sites. The primary aim of the clinical trial was to evaluate the toxicity and safety of selumetinib in patients with NF1 and inoperable plexiform neurofibromas, and, encouragingly, most of the selumetinib-related toxic effects were mild. At present, no therapies are considered effective for NF1-related large plexiform neurofibromas, but, in this trial, partial responses, meaning 20% or more reduction in tumor volume, were observed in over 70% of the patients. Responses were observed in tumors that were previously growing at a rate of greater than 20% per year, as well as in non-progressing lesions. Tumor shrinkage was maintained long term, for approximately two years, and, as of early 2016, no disease progression had been observed in any trial participant. Additionally, anecdotal evidence of clinical improvement, such as a decrease in tumor-related pain, improvement in motor function, and decreased disfigurement, was reported.


Selumetinib, provided for the study by AstraZeneca, is a selective inhibitor of the MEK protein, a part of the complex network of RAS signaling pathways. The drug has demonstrated activity in some advanced cancers, but it is not yet approved by the FDA. It is manufactured in capsule form to be taken orally.


Trial enrollment began in September 2011 and 24 children (11 girls, 13 boys) participated. Twice daily doses of the medicine were taken continuously, over a median of 30 month-long treatment cycles. The majority of patients are still continuing with therapy, some for as long as five years, and the long-term treatment has had no observed adverse effect on their development or overall health. In some patients, a loss of response to selumetinib with slow regrowth of tumors was observed, particularly after dose reductions. The authors believe that additional studies are warranted to characterize tumors that no longer respond to selumetinib. NCI is currently sponsoring an ongoing phase II trial of the drug for adults with NF1, in which serial tissue samples are being obtained. This study should provide information about possible mechanisms of resistance to selumetinib. In addition, a larger phase II pediatric trial is enrolling patients and should help establish the efficacy of selumetinib treatment in children. In this trial, in addition to tumor volume measurements, evaluations are being performed to assess the effect of selumetinib on plexiform neurofibroma related disfigurement, pain, quality of life, and function.


FDA Approves First Drug For Spinal Muscular Atrophy


Spinal muscular atrophy (SMA), is a hereditary disease that causes weakness and muscle wasting because of the loss of lower motor neurons controlling movement. There is wide variability in age of onset, symptoms and rate of progression. SMA types 1 through 4 all result from a single known cause – a deficiency of a protein called SMN, for “survival of motor neuron.“ Deficiency of SMN protein occurs when a mutation is present in both copies of the SMN1 gene one on each chromosome 5. When SMA symptoms are present at birth or by the age of 6 months, the disease is called type 1 SMA (also called infantile onset or Werdnig-Hoffmann disease). Babies typically have generalized muscle weakness, a weak cry and breathing distress. They often have difficulty swallowing and sucking, and don’t reach the developmental milestone of being able to sit up unassisted. Typically these babies have two copies of the SMN2 gene, one on each chromosome 5. Over half of all new SMA cases are SMA type 1. When SMA has its onset between the ages of 7 and 18 months and before the child can stand or walk independently, it is called type 2 or intermediate SMA. Children with type 2 SMA generally have at least three SMN2 genes. Late-onset SMA (also known as types 3 and 4 SMA, mild SMA, adult-onset SMA and Kugelberg-Welander disease) results in variable levels of weakness. Type 3 SMA has its onset after 18 months, and children can stand and walk independently, although they may require assistance. Type 4 SMA has its onset in adulthood, and people are able to walk during their adult years. People with types 3 or 4 SMA generally have between four and eight SMN2 genes, from which a fair amount of full-length SMN protein can be produced.


The FDA has approved Spinraza (nusinersen) for use across the range of SMA patients. Spinraza is the first drug approved to treat children and adults with SMA, is administered by injection into the fluid surrounding the spinal cord. The efficacy of Spinraza was demonstrated in a clinical trial in 121 patients with infantile-onset SMA who were diagnosed before 6 months of age and who were less than 7 months old at the time of their first dose. Patients were randomized to receive an injection of Spinraza, into the fluid surrounding the spinal cord, or undergo a mock procedure without drug injection (a skin prick). Twice the number of patients received Spinraza compared to those who underwent the mock procedure. The trial assessed the percentage of patients with improvement in motor milestones, such as head control, sitting, ability to kick in supine position, rolling, crawling, standing and walking.


The FDA worked closely with the sponsor during development to help design and implement the analysis upon which this approval was based. The FDA asked the sponsor to conduct an interim analysis as a way to evaluate the study results as early as possible. A total of 82 of the 121 treated patients were eligible for this analysis. Results showed that 40% of patients treated with Spinraza achieved improvement in motor milestones as defined in the study, whereas none of the control patients did. Additional open-label uncontrolled clinical studies were conducted in symptomatic patients who ranged in age from 30 days to 15 years at the time of the first dose, and in presymptomatic patients who ranged in age from 8 days to 42 days at the time of first dose. These studies lacked control groups and therefore were more difficult to interpret than the controlled study, but the findings appeared generally supportive of the clinical efficacy demonstrated in the controlled clinical trial in infantile-onset patients.


The most common side effects found in participants in the clinical trials on Spinraza were upper respiratory infection, lower respiratory infection and constipation. Warnings and precautions include low blood platelet count and toxicity to the kidneys (renal toxicity). Toxicity in the nervous system (neurotoxicity) was observed in animal studies.


The FDA granted this application fast track designation and priority review. The drug also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The sponsor is also receiving a rare pediatric disease priority review voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed by a sponsor at a later date to receive priority review of a subsequent marketing application for a different product. This is the eighth rare pediatric disease priority review voucher issued by the FDA since the program began.


Spinraza is marketed by Biogen of Cambridge, Massachusetts and was developed by Ionis Pharmaceuticals of Carlsbad, California.


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