What Makes Target Health Different From Other CROs?


TARGET HEALTH INC. is a New York City based full service eCRO with full-time staff dedicated to all aspects of Strategic Planning on How to Develop New Drugs and Devices, Regulatory Affairs, Clinical Research, Biostatistics, Data Management and Medical Writing. In addition, TARGET HEALTH has developed, and continues to develop, innovative web-based software tools that provide our clients with a significant productivity edge.


We get asked from time-to-time, “What makes Target Health different from other CROs.“ We figured that we should share this with our more than 5,100 readers of ON TARGET.


1. In the area of regulatory affairs, we are agents for 35 companies at FDA. We are very strong in regulatory strategy and the companies we represent are from all over the world.

2. We run a paperless operation and have developed integrated software tools to allow for the paperless clinical trial with associated saving of about $10,000/site/year when doing clinical trial monitoring. Our suite includes:

a. Target e*CRF® (EDC Made Simple)

b. Target e*CTR™ (eClinical Trial Record, a patented eSource solution for clinical trials)

c. Target e*Monitoring Reports™

d. Target e*Pharmacovigilance™

e. Target Document®

f. Target Encoder®

g. Target e*CTMS™

h. Target Newsletter®

3. We are able to take a drug or device from the nonclinical toxicology stage to NDA/PMA submissions.

4. We have over 35 approvals including 25 that used our EDC system. Approved products have been licensed to major pharmaceutical companies.


ON TARGET is the newsletter of Target Health Inc., a NYC-based contract research organization (CRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services, including the paperless clinical trial, to the pharmaceutical and device industries.


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.


Joyce Hays, Founder and Chief Editor of On Target

Jules Mitchel, Editor

Vanessa Hays, Editorial Contributor

Bell’s Palsy


Facial nerve: the facial nerve’s nuclei are in the brainstem. Orange: nerves coming from the left hemisphere of the brain. Yellow: nerves coming from the right hemisphere of the brain. Note that the forehead muscles receive innervation from both hemispheres of the brain (represented in yellow and orange).


Bell’s palsy is a form of facial paralysis resulting from a dysfunction of the cranial nerve VII (the facial nerve) causing an inability to control facial muscles on the affected side. Bell’s palsy is characterized by a one sided facial droop that comes on within 72 hours. Several conditions can cause facial paralysis, e.g., brain tumor, stroke, myasthenia gravis, and Lyme disease. However, if no specific cause can be identified, the condition is known as Bell’s palsy. Named after Scottish anatomist Charles Bell, who first described it, Bell’s palsy is the most common acute mononeuropathy(disease involving only one nerve) and is the most common cause of acute facial nerve 1) ___ (>80%).


Bell’s palsy is defined as an idiopathic unilateral facial nerve paralysis, usually self-limiting. The hallmark of this condition is a rapid onset of partial or complete paralysis that often occurs overnight. In rare cases (<1%), it can occur bilaterally resulting in total facial paralysis. It is thought that an inflammatory condition leads to swelling of the facial nerve. The nerve travels through the skull in a narrow bone canal beneath the ear. Nerve swelling and compression in the narrow bone canal are thought to lead to nerve inhibition, damage or death. Corticosteroids have been found to improve outcomes, when used early, while anti-viral drugs have not. Most people recover spontaneously and achieve near-normal to normal functions. Many show signs of improvement as early as 10 days after the onset, even without treatment. Often the eye in the affected side cannot be closed. The eye must be protected from drying up, or the cornea may be permanently damaged resulting in impaired 2) ___. In some cases denture wearers experience some discomfort.


The facial nerves control a number of functions, such as blinking and 3) ___ the eyes, smiling, frowning, lacrimation, salivation, flaring nostrils and raising eyebrows. They also innervate the stapedial (stapes) muscles of the middle ear and carry taste sensations from the anterior two-thirds of the tongue. Because both the nerve to the stapedius and the chorda tympani nerve (taste)are branches of the facial nerve, patients with Bell’s palsy may present with hyperacusis or loss of taste sensation in the anterior 2/3 of the tongue. The forehead 4) ___ are usually affected. Although defined as a mononeuritis (involving only one nerve), patients diagnosed with Bell’s palsy may have “myriad neurological symptoms“ including “facial tingling, moderate or severe headache/neck pain, memory problems, balance problems, ipsilateral limb paresthesias, ipsilateral limb weakness, and a sense of clumsiness“ that are “unexplained by facial nerve dysfunction“.


Some viruses are thought to establish a persistent (or latent) infection without symptoms, e.g., the varicella-zoster virus and Epstein-Barr viruses, both of the herpes family. Reactivation of an existing (dormant) viral infection has been suggested as a cause of acute Bell’s palsy. Studies suggest that this new activation could be preceded by trauma, environmental factors, and metabolic or emotional disorders, thus suggesting that a host of different conditions may trigger reactivation. Once the facial paralysis sets in, many people may mistake it as a symptom of a 5) ___. But there are a few subtle differences. A stroke will usually cause a few additional symptoms, such as numbness or weakness in the arms and legs. And unlike Bell’s palsy, a stroke will usually let patients control the upper part of their faces. A person with a stroke will usually have some wrinkling of their forehead.


One disease that may be difficult to exclude in the differential diagnosis is involvement of the facial nerve in infections with the herpes zoster virus. The major differences in this condition are the presence of small blisters, or vesicles, on the external ear and hearing disturbances, but these findings may occasionally be lacking (zoster sine herpete). Reactivation of existing herpes zoster infection leading to facial paralysis in a Bell’s palsy type pattern is known as Ramsay Hunt syndrome type 2. Lyme disease may produce the typical palsy, and may be easily diagnosed by looking for Lyme-specific antibodies in the 6) ___ or erythema migrans. In endemic areas Lyme disease may be the most common cause of facial palsy.




Babies can be born with facial palsy. In a few cases, bilateral facial palsy has been associated with acute HIV infection. In some research, the herpes simplex virus type 1 (HSV-1) has been identified in a majority of cases diagnosed as Bell’s palsy. This has given hope for anti-inflammatory and anti-viral drug therapy (prednisone and acyclovir). Other research, however, identifies HSV-1 in only 31 cases (18%), herpes zoster (zoster sine herpete) in 45 cases (26%) in a total of 176 cases clinically diagnosed as Bell’s Palsy. That infection with herpes simplex virus should play a major role in cases diagnosed as Bell’s palsy therefore remains a hypothesis that requires further research. In addition, the herpes simplex virus type 1 (HSV-1) infection is associated with demyelination of nerves. This 7) ___ damage mechanism is different from the above mentioned – that edema, swelling and compression of the nerve in the narrow bone canal is responsible for nerve damage. Demyelination may not even be directly caused by the virus, but by an unknown immune system response.


Bell’s palsy is a diagnosis of exclusion, meaning it is diagnosed by elimination of other reasonable possibilities. By definition, no specific cause can be determined. There are no routine lab or imaging tests required to make the diagnosis. The degree of nerve damage can be assessed using the House-Brackmann score. One study found that 45% of patients are not referred to a specialist, which suggests that Bell’s palsy is considered by physicians to be a straightforward diagnosis that is easy to manage. Other conditions that can cause similar symptoms include: herpes zoster, sarcoidosis, and brain tumors. Steroids have been shown to be effective at improving recovery in Bell’s palsy while antivirals have not. In those who are unable to close their eyes, eye protective measures are required. Corticosteroid such as 8) ___ significantly improves recovery at 6 months and are thus recommended. Early treatment (within 3 days after the onset) is necessary for benefit with a 14% greater probability of recovery. Antivirals (such as acyclovir) are ineffective in improving recovery from Bell’s palsy beyond steroids alone. They were however commonly prescribed due to a theoretical link between Bell’s palsy and the herpes simplex and varicella zoster virus. There is still the possibility that they might result in a benefit less than 7% as this has not been ruled out.


Physiotherapy can be beneficial to some individuals with Bell’s palsy as it helps to maintain muscle tone of the affected facial muscles and stimulate the facial nerve. It is important that muscle re-education exercises and soft tissue techniques be implemented prior to recovery in order to help prevent permanent contractures of the paralyzed facial muscles. To reduce 9) ___, heat can be applied to the affected side of the face. Surgery may be able to improve outcomes in facial nerve palsy that has not recovered. A number of different techniques exist. Smile surgery or smile reconstruction is a surgical procedure that may restore the smile for people with facial nerve paralysis. It is unknown if early surgery is beneficial or harmful. Adverse effects include hearing loss which occurs in 3-15% of people. As of 2007 the American Academy of Neurology did not recommend surgical decompression. The efficacy of acupuncture remains unknown because the available studies are of low quality (poor primary study design or inadequate reporting practices).


Most people with Bell’s palsy start to regain normal facial function within 3 weeks, even those who do not receive treatment. In a 1982 study, when no treatment was available, of 1,011 patients, 85% showed first signs of recovery within 3 weeks after onset. For the other 15%, recovery occurred 3-6 months later. After a follow-up of at least 1 year or until restoration, complete recovery had occurred in more than two-thirds (71%) of all patients. Recovery was judged moderate in 12% and poor in only 4% of patients. Another study found that incomplete palsies disappear entirely, nearly always in the course of one month. The patients who regain movement within the first two weeks nearly always remit entirely. When remission does not occur until the third week or later, a significantly greater part of the patients develop sequelae. A third study found a better prognosis for young patients, aged below 10 years old, while the patients over 61 years old presented a worse prognosis.


Major complications of the condition are chronic loss of taste (ageusia), chronic facial spasm, facial pain and corneal infections. To prevent the latter, the eyes may be protected by covers, or taped shut during sleep and for rest periods, and tear-like eye drops or eye ointments may be recommended, especially for cases with complete paralysis. Where the eye does not close completely, the blink reflex is also affected, and care must be taken to protect the eye from injury. Another complication can occur in case of incomplete or erroneous regeneration of the damaged facial nerve. The nerve can be thought of as a bundle of smaller individual nerve connections that branch out to their proper destinations. During regrowth, nerves are generally able to track the original path to the right destination – but some nerves may sidetrack leading to a condition known as synkinesis. For instance, regrowth of nerves controlling muscles attached to the eye may sidetrack and also regrow connections reaching the muscles of the mouth. In this way, movement of one also affects the other. For example, when the person closes the eye, the corner of the mouth lifts involuntarily.


Around 9% of patients have some sort of sequelae after Bell’s palsy, typically the synkinesis already discussed, or spasm, contracture, tinnitus and/or hearing loss during facial movement or crocodile tear syndrome. This is also called gustatolacrimal reflex or Bogorad’s Syndrome and involves the sufferer shedding 10) ___ while eating. This is thought to be due to faulty regeneration of the facial nerve, a branch of which controls the lacrimal and salivary glands. Gustatorial sweating can also occur.


The annual incidence of Bell’s palsy is about 20 per 100,000 population, and the incidence increases with age. Bell’s palsy affects about 40,000 people in the United States every year. It affects approximately 1 person in 65 during a lifetime. Familial inheritance has been found in 4-14% of cases. Bell’s palsy is three times more likely to strike 11) ___ women than non-pregnant women. It is also considered to be four times more likely to occur in diabetics than the general population.


A range of annual incidence rates have been reported in the literature: 15, 24, and 25-53 (all rates per 100,000 population per year). Bell’s palsy is not a reportable disease, and there are no established registries for patients with this diagnosis, which complicates precise estimation. Although it is named after Sir Charles 12) ___, the Scottish anatomist who provided the first anatomic basis for trigeminal neuralgia and facial palsy, other European physicians provided earlier clinical descriptions of peripheral cranial nerve 7 palsy. In a recent review article describing history of facial palsy by Greek, Roman, and Persian physicians. Cornelis Stalpart van der Wiel (1620-1702) in 1683 gave an account of Bell’s palsy and credited Avicenna (980-1037) for describing this condition before him. James Douglas (1675-1742) and Nicolaus Anton Friedreich (1761-1836) also described it. One well known television personality with Bell’s Palsy is lawyer, Greta Van Susteren.


ANSWERS: 1) paralysis; 2) vision; 3) closing; 4) muscles; 5) stroke; 6) blood; 7) nerve; 8) prednisone; 9) pain; 10) tears; 11) pregnant; 12) Bell

Sir Charles Bell MD (1774-1842)




Engraving by Charles Bell MD


Charles Bell was a Scottish anatomist and physician whose, New Idea of Anatomy of the Brain (1811) has been called the “Magna Carta of neurology.“ Born at Edinburgh in November 1774, the youngest son of the Rev. William Bell, a clergyman of the Episcopal Church of Scotland; among his brothers were the anatomist, John Bell, and the jurist, G. J. Bell. After attending the high school and the University of Edinburgh, he embraced the profession of medicine, and devoted himself chiefly to the study of anatomy, under the direction of his brother John. His first work, entitled A System of Dissections, explaining the anatomy of the human body, the manner of displaying the parts, and their varieties in disease, was published in Edinburgh in 1798, while he was still a pupil, and for many years was considered to be a valuable guide to the student of practical anatomy.


In 1802 he published a series of engravings of original drawings, showing the anatomy of the brain and nervous system. These drawings, which are remarkable for artistic skill and finish, were taken from dissections made by Bell for the lectures or demonstrations he gave on the nervous system as part of the course of anatomical instruction of his brother. In 1804 he wrote the third volume, containing the anatomy of the nervous system and of the organs of special sense, of The Anatomy of the Human Body, by John and Charles Bell. In November of the same year he migrated to London, and from that date, for nearly forty years, he kept up a regular correspondence with his brother George, much of which was published in the Letters of Sir Charles Bell, etc., 1870. The earlier letters of this correspondence show how rapidly he rose to distinction in a field where success was difficult, as it was already occupied by such men as John Abernethy, Sir Astley Cooper and Henry Cline. Before leaving Edinburgh, he had written his work on the Anatomy of Expression, which was published in London soon after his arrival and at once attracted attention. His practical knowledge of anatomy and his skill as an artist qualified him in an exceptional manner for such a work. The object of this treatise was to describe the arrangements by which the influence of the mind is propagated to the muscular frame, and to give a rational explanation of the muscular movements which usually accompany the various emotions and passions. One special feature was the importance attributed to the respiratory arrangements as a source of expression, and it was shown how the physician and surgeon might derive information regarding the nature and extent of important diseases by observing the expression of bodily suffering. This work, apart from its value to artists and psychologists, is of interest historically, as there is no doubt the investigations of the author into the nervous supply of the muscles of expression induced him to prosecute inquiries which led to his great discoveries in the physiology of the nervous system.


In 1811 Bell published his New idea of the Anatomy of the Brain, in which he announced the discovery of the different functions of the nerves corresponding with their relations to different parts of the brain; his latest researches were described in The Nervous System of the Human Body (1830), a collection of papers read by him before the Royal Society. He discovered that in the nervous trunks there are special sensory filaments, the office of which is to transmit impressions from the periphery of the body to the sensorium, and special motor filaments which convey motor impressions from the brain or other nerve center to the muscles. He also showed that some nerves consist entirely of sensory filaments and are therefore sensory nerves, that others are composed of motor filaments and are therefore motor nerves, while a third variety contains both kinds of filaments and are therefore to he regarded as sensory-motor. Furthermore, he indicated that the brain and spinal cord may be divided into separate parts, each part having a special function — one part ministering to motion, the other to sensation, and that the origin of the nerves from one or other or both of those sources endows them with the peculiar property of the division, from which they spring. He also demonstrated that no motor nerve ever passes through a ganglion. Lastly, he showed, both from theoretical considerations and from the result of actual experiment on the living animal, that the anterior roots of the spinal nerves are motor, while the posterior are sensory. These discoveries as a whole must be regarded as the greatest in physiology since that of the circulation of the blood by William Harvey. They were not only a distinct and definite advance in scientific knowledge, but from them flowed many practical results of much importance in the diagnosis and treatment of disease. It is not surprising that Bell should have viewed his results with exultation. On the 26th of November 1807, he wrote to his brother George: “I have done a more interesting nova anatomia cerebri humani than it is possible to conceive. I lectured it yesterday. I prosecuted it last night till one o’clock; and I am sure it will be well received.“ On the 31st of the same month he wrote: “I really think this new anatomy of the brain will strike more than the discovery of the lymphatics being absorbents.“


In 1807 he produced a System of Comparative Surgery, in which surgery is regarded almost wholly from an anatomical and operative point of view, and there is little or no mention of the use of medicinal substances. It placed him, however, in the highest rank of English writers on surgery. In 1809 he relinquished his professional work in London, and rendered meritorious services to the wounded from Coruna, who were brought to the Haslar hospital at Portsmouth. In 1810 he published a series of Letters concerning the Diseases of the Urethra, in which he treated a stricture from an anatomical and pathological point of view. In 1812 he was appointed surgeon to the Middlesex hospital, a post he retained for 24 years. He was also professor of anatomy, physiology and surgery to the College of Surgeons of London, and for many years teacher of anatomy in the school which used to exist in Great Windmill Street. In 1815 he went to Brussels to treat the wounded of the battle of Waterloo. In 1816, 1817 and 1818, he published a series of Quarterly Reports of Cases in Surgery; in 1821 a volume of colored plates with descriptive letterpress, entitled Illustrations of the great operations of Surgery, Trepan, Hernia, Amputalion and Lithotomy, and in 1824 Observations on Injuries of the Spine and of the Thigh Bone. On the formation of University College, Gower Street, he was for a short time head of the medical department. In 1832 he wrote a paper for the Royal Society of London on the “Organs of the Human Voice“, in which he gave many illustrations of the physiological action of these parts, and in 1833 a Bridgewater treatise, The Hand: its Mechanism and Vital Endowments as evincing Design. Along with Lord Brougham he annotated and illustrated an edition of Paley’s Natural Theology, published in 1836. The Royal Society of London awarded to him in 1829 the first annual medal of that year given by King George IV for discoveries in science; and when King William IV ascended the throne, Charles Bell received the honor of knighthood along with a few other men distinguished in science and literature.


In 1836 the chair of surgery in the University of Edinburgh was offered to him. He was then one of the foremost scientific men in London, and he had a large surgical practice. But his opinion was “London is a place to live in, but not to die in“; and he accepted the appointment. In Edinburgh he did not earn great local professional success; and, it must be confessed, he was not appreciated as he deserved. But honors came thick upon him. On the continent of Europe he was spoken of as greater than Harvey. It is narrated that one day P.J. Roux, a celebrated French physiologist, dismissed his class without a lecture, saying “C’est assez, messieurs, vous avez vu Charles Bell.“ During his professorship he published the Institutes of Surgery, arranged in the order of the lectures delivered in the University of Edinburgh (1838); and in 1841 he wrote a volume of Practical Essays, two of which, “On Squinting“, and “On the action of purgatives“, are of great value. He died at Hallow Park near Worcester on the 28th of April 1842.


Bell served as a military surgeon, making elaborate recordings of neurological injuries at the Royal Hospital Haslar and famously documenting his experiences at Waterloo in 1815. Bell was also instrumental in the creation of the Middlesex Hospital Medical School, and became, in 1824, the first professor of Anatomy and Surgery of the College of Surgeons in London. In 1829, the Windmill Street School of Anatomy was incorporated into the new King’s College London. Bell was invited to be its first professor of physiology. Bell’s studies on emotional expression, flawed though they were, played a catalytic role in the development of Darwin’s considerations of the origins of human emotional life; and Darwin very much agreed with Bell’s emphasis on the expressive role of the muscles of respiration. Darwin detailed these opinions in his The Expression of the Emotions in Man and Animals (1872), written with the active collaboration of the psychiatrist James Crichton-Browne. Bell was one of the first physicians to combine the scientific study of neuroanatomy with clinical practice. In 1821, he described in the trajectory of the facial nerve and a disease, Bell’s Palsy which led to the unilateral paralysis of facial muscles, in one of the classics of neurology, a paper to the Royal Society entitled On the Nerves: Giving an Account of some Experiments on Their Structure an Functions, Which Lead to a New Arrangement of the System.


Bell also combined his many artistic, scientific, literary and teaching talents in a number of wax preparations and detailed anatomical and surgical illustrations, paintings and engravings in his several books on these subjects, such as in his book Illustrations of the Great Operations of Surgery: Trepan, Hernia, Amputation, Aneurism, and Lithotomy (1821). He wrote also the first treatise on notions of anatomy and physiology offacial expression for painters and illustrators, titled Essays on the Anatomy of Expression in Painting (1806). In 1833 he published the fourth Bridgewater Treatise, The Hand: Its Mechanism and Vital Endowments as Evincing Design.


A number of discoveries received his name:

  1. Bell’s (external respiratory) nerve: The long thoracic nerve.

  2. Bell’s palsy: a unilateral idiopathic paralysis of facial muscles due to a lesion of the facial nerve.

  3. Bell’s phenomenon: A normal defense mechanism — upward and outward movement of the eye which occurs when an individual closes their eyes forcibly. It can be appreciated clinically in a patient with paralysis of the orbicularis oculi (e.g. Guillain-Barre or Bell’s palsy), as the eyelid remains elevated when the patient tries to close the eye.

  4. Bell’s spasm: Involuntary twitching of the facial muscles.

  5. Bell-Magendie law or Bell’s Law: States that the anterior branch of spinal nerve roots contain only motor fibers and the posterior roots contain only sensory fibers.


Wishing to return to Scotland, he accepted in 1836 the position of Professor of Surgery at the University of Edinburgh. Bell died in the Midlands, travelling back from Edinburgh to London, in 1842.

Why Does the Incidence of Cancer Increase With Age


DNA methylation is one of several epigenetic mechanisms that can control gene expression without changes in DNA sequence.


It has been known for years that age is a leading risk factor for the development of many types of cancer, but why aging increases cancer risk remains unclear. Researchers suspect that DNA methylation, or the binding of chemical tags, called methyl groups, onto DNA, may be involved. Methyl groups activate or silence genes, by affecting interactions between DNA and the cell’s protein-making machinery. According to an article published online in the journal Carcinogenesis (28 November 2013), the accumulation of age-associated changes in a biochemical process that helps control genes may be responsible for some of the increased risk of cancer seen in older people. The study identified DNA methylation sites across the human genome that changed with age and demonstrated that a subset of those sites — the ones that become increasingly methylated with advancing age — are also disproportionately methylated in a variety of human cancers.


According to the authors one can think of methylation as dust settling on an unused switch, which then prevents the cell from turning on certain genes; and if a cell can no longer turn on critical developmental programs, it might be easier for it to become a cancer cell.


The study used blood samples from participants in the Sister Study, a nationwide research effort to find the environmental and genetic causes of breast cancer and other diseases. More than 50,000 sisters of women who have had breast cancer are participating in the study. The study analyzed blood samples from 1,000 women, using a microarray that contained 27,000 specific methylation sites. Results showed that nearly one-third of the sites showed increased DNA methylation in association with age. They then looked at three additional data sets from smaller studies that used the same microarray and found 749 methylation sites that behaved consistently across all four data sets. As an additional check, the authors consulted methylation data from normal tissues and seven different types of cancerous tumors in The Cancer Genome Atlas, a database funded by the National Cancer Institute and the National Human Genome Research Institute.


The authors hypothesized that DNA methylation appears to be part of the normal aging process and occurs in genes involved in cell development. Cancer cells often have altered DNA methylation, but the authors were surprised to find that 70-90% of the sites associated with age showed significantly increased methylation in all seven cancer types. This suggested that age-related methylation may disable the expression of certain genes, making it easier for cells to transition to cancer. The study also determined how fast these methylation events accumulate in cells and found that they occur at a rate of one per year.


For future work, the authors want to examine more samples, using a newer microarray that will explore methylation at 450,000 genomic methylation sites. The additional samples and larger microarray, which will provide 16 times more genomic coverage, will allow them to address whether environmental exposures during adulthood or infancy affect methylation profiles. These additional studies will help scientists better understand why methylation happens as people march toward their retirement years.

Multiple Phenotypes in Phosphoglucomutase 1 Deficiency

Congenital disorders of glycosylation are genetic syndromes that result in impaired glycoprotein production.


A study published in the New England Journal of Medicine (2014;370:533-542) evaluated patients who had a novel recessive disorder of glycosylation, with a range of clinical manifestations that included hepatopathy, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, and cardiac arrest.


For the study, homozygosity mapping followed by whole-exome sequencing was used to identify a mutation in the gene for phosphoglucomutase 1 (PGM1) in two siblings. Sequencing identified additional mutations in 15 other families. Phosphoglucomutase 1 enzyme activity was assayed on cell extracts. Analyses of glycosylation efficiency and quantitative studies of sugar metabolites were performed. Galactose supplementation in fibroblast cultures and dietary supplementation in the patients were studied to determine the effect on glycosylation.


Results showed that phosphoglucomutase 1 enzyme activity was markedly diminished in all patients. Mass spectrometry of transferrin showed a loss of complete N-glycans and the presence of truncated glycans lacking galactose. Fibroblasts supplemented with galactose showed restoration of protein glycosylation and no evidence of glycogen accumulation. Dietary supplementation with galactose in six patients resulted in changes suggestive of clinical improvement. A new screening test showed good discrimination between patients and controls.


According to the authors, phosphoglucomutase 1 deficiency, previously identified as a glycogenosis, is also a congenital disorder of glycosylation., and that supplementation with galactose leads to biochemical improvement in indexes of glycosylation in cells and patients. In addition, supplementation with complex carbohydrates stabilizes blood glucose. While a new screening test has been developed, it has not yet been validated.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.


Why FDA Supports a Flexible Approach to Drug Development 

Target Health is thrilled that Dr. Margaret Hamburg quoted the approval of Elelyso (taliglucerase alfa) – for Gaucher disease as an example of FDA’s flexible approach to drug development. Target Health worked strategically with Protalix Biotherapeutics beginning in 2006, and managed the regulatory, nonclinical and clinical programs for this project. FDA approved this orphan drug in 2012 based on two trials with 56 patients.  Elelyso is marketed by Pfizer.


The following is based on Dr. Hamburg’s post in FDA Voice on February 6, 2014.



Margaret A. Hamburg, M.D., Commissioner of the US FDA


We all know that just as every person is different, so too is every disease and every drug. And so FDA was not surprised by the results of a new study published in the Journal of the American Medical Association. The study found that FDA used a range of clinical trial evidence when approving 188 novel therapeutic drugs for 208 indications (uses) between 2005 and 2012. According to Dr. Hamburg, these results are entirely consistent with their regulatory mandate and that these varying approaches to clinical studies to support drug approval is good news, rather than bad news.


Results from the publication in JAMA showed that data to support the approvals were based on a median of two pivotal trials per indication. A pivotal trial presents the most important data used by FDA to decide whether to approve a drug. But when the authors looked more closely, they found that more than a third of these drugs were approved on the basis of a single pivotal clinical trial, while still other trials involved only small groups of patients for shorter durations. Of the approvals studied, the new drug was compared with existing drugs on the market only about 40% of the time. The authors concluded that, based on these results, the ways in which FDA arrived at those approvals “vary widely in their thoroughness.“ Or, in the words of one study author, “Not all FDA approvals are created equally.“ While Dr. Hamburg does think it was actually the author’s intent, a number of commentators framed this as criticism. But Dr. Hamburg said that would be more troubling if FDA used a rigid, “one size fits all“ approach.


People with serious or life-threatening illnesses, particularly those who lack good alternatives, have told FDA repeatedly that they are willing to make some trade-offs in order to gain access. And, of course, “thoroughness,“ such as whether a clinical trial is large enough, is in the eyes of the beholder. There is no reason to expect drugs to be tested on similar numbers of patients, regardless of the disease.


According to Dr. Hamburg, variation in approach to clinical studies demonstrates FDA’s innovative and flexible approach to drug development and approvals. Such an approach was specifically adopted by Congress in the Food and Drug Administration Modernization Act in 1997 and, most recently, in the Food and Drug Administration Safety and Innovation Act in 2012. The FDA of today works with sponsors of new drugs to design a development and review pathway for each drug that best reflects the disease and patients it is intended to treat, the drug itself, and other treatment options. Some of the factors that enter into the calculus include whether the drug treats a rare or serious disease or addresses an unmet need and any previous knowledge we might have about the drug.


Thus, for example, FDA approved Imbruvica (ibrutinib), a treatment for mantle cell lymphoma, last year based on an “open-label, single-arm trial,“ which means that every patient received the treatment and both patients and researchers knew they were receiving it. The results were compared to how well the 111 participating patients had responded to previous treatment for their disease.


And Elelyso (taliglucerase alfa) – for Gaucher disease – was an orphan drug approved in 2012 based on two trials with 56 patients.


In contrast, some trials require large numbers of patients to demonstrate a drug’s effects. This is often the case in studies in patients with a chronic condition such as cardiovascular disease, where larger populations are studied to capture treatment effects. No matter what clinical trial design is chosen, the FDA always applies the same statutory approval standards of safety and efficacy to all drugs seeking to be marketed in the United States.


Increased flexibility does not mean abandoning standards, and it certainly does not mean abandoning science. Just the opposite. FDA needs to employ the best science in ways that will increase efficiency, productivity and its shared ability to find creative solutions to the challenges that confront us. At the end of the day, that is just smart regulation – ensuring that patients can more rapidly have access to the best that science has to offer.

Garlicky Orange Salad with Marcona Almonds, Black Olives and Spices


©Joyce Hays, Target Health Inc.


To lift you out of your winter doldrums, here is a sparkly salad that will perk you and your family up. Its bright hues and dark/light color contrasts, will lift your spirits. Your first bite of crunchy fresh ingredients will please your palate. If your taste buds are willing to accept a mild swirl of spice, enabling the earthiness of olives to mix with the sweetness of oranges (and the pronounced almond flavor of the gourmet Marconas). then, you’re in for an adventure in juxtaposed textures and flavors.


5 navel oranges, peeled and diced
1 cup black salt-cured olives (I used Kalamata), pitted and cut in half
2 or 3 cloves garlic, minced (3 if you love garlic)
1/4 teaspoon kosher salt (optional)
2/3 cup fresh parsley, chopped (next time I’ll use fresh cilantro)
1 teaspoon sweet paprika
1/2 teaspoon ground cumin
Pinch cayenne pepper
2 Tablespoons extra-virgin olive oil
1 cup Marcona almonds, toasted

Combine all the ingredients in a bowl and toss well. Refrigerate to chill, then serve.


Believe it or not, this is easy and quick to make. I would suggest that this beautiful salad, become part of a totally veggie meal. Serve a chilled white wine, (we had a California Sauvignon blanc). with hummus and warm pita bread. Then the Orange/Almond/Olive salad. Serve your favorite pasta, like cappellini with pesto, and an assortment of cheeses with red grapes for dessert. (If you do want a protein, then serve a light white fish, or consider seafood)




Toast to Health, Love and Friendship!