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Male Hypogonadism – Cleveland Clinic

Definition and Prevalence

Male hypogonadism is defined as the failure of the testes to produce androgen, sperm, or both. Although the disorder is exceedingly common, its exact prevalence is uncertain.

Testosterone production declines with advancing age; 20% of men older than 60 years and 30% to 40% of men older than 80 years have serum testosterone levels that would be subnormal in their younger adult male counterparts. This apparent physiologic decline in circulating androgen levels is compounded in frequency by permanent disorders of the hypothalamic-pituitary-gonadal axis (see later). These include the transient deficiency states associated with acute stressful illnesses, such as surgery and myocardial infarction, and the more chronic deficiency states associated with wasting illnesses, such as cancer and acquired immunodeficiency syndrome.

Male factor infertility is probably responsible for one third of the 10% to 15% of couples who are unable to conceive within 1 year of unprotected intercourse. Most of these male-associated cases result from diminished, absent, or faulty spermatogenesis. In addition to abnormal sperm production, other conditions, including obstructive ductal disease, epididymal hostility, immunologic disorders, and erectile or ejaculatory dysfunction should be considered. Finally, because combined female-male infertility is common, and fertility as well as psychological well-being are ultimate goals, both partners must be assessed from the outset.

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The physiologic regulation of the hypothalamic-pituitary-gonadal axis is shown in Figure 1. Circulating testosterone is largely protein-boundthe major protein is sex hormonebinding globulin (SHBG)with only 2% present as the biologically active or free fraction. Some clinicians believe that the bioavailable fraction, the fraction present in the supernatant after ammonium sulfate precipitation, representing testosterone loosely bound predominantly to serum albumin, is more meaningful. Hepatic SHBG production rises with aging and thyroid hormone excess and declines in hyperinsulinemic states (obesity and type 2 diabetes), so that free testosterone values may not always be concordant with total testosterone values. The biologic effects of testosterone may be mediated directly by testosterone or by its metabolites 5-dihydrotestosterone or estradiol (Fig. 2).

Male hypogonadism is caused by a primary (hypergonadotropic) testicular disorder or is secondary (hypo- or normogonadotropic) to hypothalamic-pituitary dysfunction, as illustrated in Figure 3. Combined disorders also occur. Examples of the major causes of male hypogonadism are shown in Boxes 1 and 2.

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Persistent failure of the testes to descend may be an early manifestation of testicular dysfunction. In addition, a normally formed but hypotrophic penis may provide a clue to an abnormality of the hypothalamic-pituitary-gonadal axis.

Delayed, arrested, or absent testicular growth and secondary sexual characteristic development are hallmarks of pubertal disorders. Skeletal proportions may be abnormal (eunuchoid) with more than a 5-cm difference between span and height and between pubis-floor and pubis-vertex dimensions.

Manifestations in adults are generally more subtle. Perhaps the minor contribution of adrenal androgens (or androgenic precursors) may substitute for testicular deficiency once the target tissues have been fully developed. Moreover, ingrained behavior patterns may be resistant to androgenic hormone deficiency. Certainly, prolactin excess, testosterone deficiency, or both in men may result in impaired libido and erectile dysfunction. The yield of finding hyperprolactinemia or testosterone deficiency, or both, in patients presenting with these symptoms is generally considered to be low, usually less than 5%. However, a large survey of patients with erectile dysfunction presenting to a Veterans Affairs center has suggested that the prevalence of these abnormalities is substantial: 18.7% of patients with low testosterone levels and 4.6% with elevated prolactin levels.1

The first manifestation of hypogonadism may be a consequence of a large space-occupying intrasellar or parasellar lesion manifested by headaches, bitemporal hemianopia, or extraocular muscle palsy. Galactorrhea as a manifestation of hyperprolactinemia is rare, but rarely sought. Unexplained osteoporosis or mild anemia sometimes is the clue to an underlying hypogonadal state. Some common clinical conditions associated with male hypogonadism are listed in Box 3. The subject of androgen deficiency and the aging man is dealt with in greater detail later in this chapter.

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Because of the well-known diurnal rhythm of serum testosterone, which appears to be lost with age (>60 years), with values 30% or so higher near 8 am versus the later day trough, a testosterone value should be determined first thing in the morning. Normal ranges vary among laboratories. Although the usually quoted range for young men is 300 to 1000ng/dL, the lower limit reported for the Cleveland Clinic is 220ng/dL. In general, values below 220 to 250ng/dL are clearly low in most laboratories; values between 250 and 350ng/dL should be considered borderline low. Because the acute effect of stressful illness may result in a transient lowering of testosterone levels, a confirmatory early morning specimen should be obtained. Measurement of free testosterone levels or bioavailable testosterone levels, determined adequately in select commercial laboratories, may provide additional information (see later, Pathophysiology). For example, free testosterone levels may be lower than expected from the total testosterone level as a result of aging and higher than expected in insulin-resistant individuals, such as in obesity. In addition, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels should be determined to help delineate the cause of the testosterone-deficient state.

If gonadotropin levels are not elevated, despite clearly subnormal testosterone values, anterior pituitary (thyroid-adrenal) function should be determined by measuring free thyroxine and thyroid-stimulating hormone levels, as well as an early morning cortisol level. A magnetic resonance imaging (MRI) scan of the brain and sella should be considered. An exception to this recommendation is the condition of morbid obesity, in which both total and free testosterone levels are typically low and gonadotropin values not elevated. Hyperprolactinemia, even of a small degree, may also warrant ordering MRI, because interference of hypothalamic-pituitary vascular flow by space-occupying, stalk-compressing lesions will lead to disruption of the tonic inhibitory influence of hypothalamic dopamine, and result in modest hyperprolactinemia (usually 20 to 50 ng/mL range).

A semen analysis should be performed when fertility is in question.

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Androgen replacement therapy is relatively straightforward; see Box 4 for testosterone preparations currently available in the United States. Typically, the depot esters are administered by the deep intramuscular route once every 2 weeks at a dose of 200mg in adults. A usual dosage for the transdermal or the buccal preparations results in the systemic absorption of 2.5 to 10mg daily. If the parenteral route is chosen, patients should and can be taught to self inject. The major disadvantage with the parenteral route is that testosterone levels exhibit a saw-toothed pattern, with high-normal or supranormal levels on days 2 to 4 and low-normal or borderline low trough values before the next injection. Mood, sense of well-being, and libido may vary accordingly in some patients.

Dosages may be adjusted by aiming for midnormal (400- 600ng/dL) testosterone levels after 1 week or at the low end (250-350ng/dL) just before the next injection is due at 2 weeks. Values are stable within a few days or weeks of the skin patch, gel, or newer buccal preparation. It must be ascertained that the preparation was actually used on the day the sample was drawn; again, a value in the midnormal range (400-600ng/dL) is the goal. Although comparable testosterone levels are reached by the patch and the gels, skin reactions at the application site are much more common with the patch. Also, the buccal preparation is difficult for patients to get used to. Alkylated oral androgens should be viewed as potentially hepatotoxic and should not be used. Useful criteria for selecting preparations for individual patients are summarized in Table 1.

+, ++, and +++ are semiquantitative assessments of effect.

2002 The Cleveland Clinic Foundation.

In addition to monitoring testosterone levels periodically, prostate screening and measurement of hemoglobin and hematocrit levels must also be performed at intervals when the patient is on therapy.2

Levels of prostate-specific antigen (PSA) should be checked at 3, 6, and 12 months. If the patient is truly hypogonadal to begin with, expect a significant rise at the 3-month assessment. Thereafter, the usual criteria apply regarding the possible presence of an underlying malignancy (>4ng/mL, or rate of increase >1.5ng/mL/2yr or >2ng/mL overall). These criteria continue to be revised by our urology colleagues, tending to become more stringent with time. For example, a PSA rise of more than 1ng/mL/year has been suggested as an early warning guide, and closer surveillance has been recommended, even at rates of 0.7 to 0.9ng/mL/year.2 A digital rectal examination should be performed at 3 to 6 months and at 1 year after therapy is initiated. A urologic consultation should be obtained if indicated.

Hemoglobin (Hb) and hematocrit (Hct) levels should be checked periodically. Incremental increases are to be expected, but an Hb level higher than 17.5g/dL, Hct higher than 55%, or both suggests overtreatment, occasionally abuse. Greater increments tend to occur more frequently with the intramuscular than with the transdermal preparations. If dosage adjustments do not solve the problem, look for another underlying cause.

Physicians Box 5). It should be noted that no long- term studies in large numbers of patients (neither young or old) have been performed, so potential risks and benefits need to be individualized.

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In genuinely hypogonadal men, testosterone administration can be expected to result in improvements in a variety of clinical areas (Box 6). Least predictable are the effects on sexual function, cognitive function, and muscle strength.

2002 The Cleveland Clinic Foundation.

Concerns regarding the use of testosterone have been noted in Box 5 and by Rhoden and Morgentaler.2 There is no evidence that the incidence of prostate cancer is increased by testosterone replacement. The underlying concern is that it might alter the course of an occult malignancy estimated to be present in more than 50% of men older than 50 years. On the other hand, no one would recommend prophylactic castration to prevent prostate cancer so that, in my view, testosterone replacement in the hypogonadal man should not be avoided. Although there are genuine concerns about worsening of benign prostatic hyperplasia, this may apply only to severe cases with large prostate volumes. Indeed, one study in older men has even suggested improvement in benign prostatic hyperplasia symptoms, although not statistically significant and by an unknown mechanism.3

The aging man represents a special case and has been the subject of a review.4 There is a well-known decline in testosterone production with aging in otherwise healthy men. This decline in mean values can be seen in free testosterone levels, beginning in the mid-40s (some clinicians suggest even earlier), as a consequence of increasing SHBG levels, mechanism unknown. Total testosterone levels decline on average beyond 70 years. The diurnal rhythm, seen in younger men, is lost beyond 60 years.5 Although testicular volume also declines in this age group, spermatogenesis may be well maintained into the 80s or even beyond. Gonadotropin levels tend to rise after 70 years, indicating that the testosterone deficiency is usually primary.6Figure 4 schematically presents these hormonal changes with age. Using the criterion of a low testosterone value, and remembering that there is considerable variability in commercially available tests regarding normal young adult ranges, it has been estimated that 7% of 40- to 60-year-olds, 22% of 60- to 80-year-olds, and 36% of 80- to 100-year-olds are hypogonadal.7

The ultimate issue as to whether these changes are normal and physiologic or should be considered pathologic, thus demanding therapy, remains unresolved. Indeed, it is a situation analogous to the ongoing dilemma of hormone replacement therapy for postmenopausal women, although in this group the hormonal deficiency state is usually more abrupt and symptomatic.

The scientific basis to help formulate guidelines for dealing with the issue of hormone replacement therapy in men was reviewed in a December 17, 2003, conference by the Institute of Medicines Committee on Testosterone and Aging (IMCTA).8 Many of the potential benefits of therapy (see Box 6) have been realized in small, well-controlled studies of older men. Moreover, none of the risks has been proven in a clinical trial. The IMCTA has not recommended a large-scale study to determine whether the risk for prostate cancer would be increased, because the costs of such a study were deemed to be too prohibitive.

In the meantime, practical guidelines for dealing with hypogonadism in older men have been suggested.9 I have found the recent overview in the Cleveland Clinic Mens Health Advisor newsletter to be useful for patients.10

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The American Association of Clinical Endocrinologists has published 2002 updated guidelines for the evaluation and treatment of hypogonadism in adult male patients.11 This review, geared particularly for endocrinologists, expands on some of the areas reviewed in this chapter and provides a more detailed look into aspects of male infertility.

The Endocrine Society has published clinical practice guidelines12 for testosterone replacement therapy. The major recommendations are summarized in Box 7.

Adapted from Bhasin S, Cunningham GR, Hayes FJ, etal: Testosterone therapy in adult men with androgen deficiency syndromes: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006;91:1995-2010.

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Male Hypogonadism – Cleveland Clinic

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genetics |

Genetics,chromosomeCreated and produced by QA International. QA International, 2010. All rights reserved. of heredity in general and of genes in particular. Genetics forms one of the central pillars of biology and overlaps with many other areas such as agriculture, medicine, and biotechnology.

Since the dawn of civilization, humankind has recognized the influence of heredity and has applied its principles to the improvement of cultivated crops and domestic animals. A Babylonian tablet more than 6,000 years old, for example, shows pedigrees of horses and indicates possible inherited characteristics. Other old carvings show cross-pollination of date palm trees. Most of the mechanisms of heredity, however, remained a mystery until the 19th century, when genetics as a systematic science began.

Crick, Francis Harry Compton: proposed DNA structureEncyclopdia Britannica, Inc.Genetics arose out of the identification of genes, the fundamental units responsible for heredity. Genetics may be defined as the study of genes at all levels, including the ways in which they act in the cell and the ways in which they are transmitted from parents to offspring. Modern genetics focuses on the chemical substance that genes are made of, called deoxyribonucleic acid, or DNA, and the ways in which it affects the chemical reactions that constitute the living processes within the cell. Gene action depends on interaction with the environment. Green plants, for example, have genes containing the information necessary to synthesize the photosynthetic pigment chlorophyll that gives them their green colour. Chlorophyll is synthesized in an environment containing light because the gene for chlorophyll is expressed only when it interacts with light. If a plant is placed in a dark environment, chlorophyll synthesis stops because the gene is no longer expressed.

Genetics as a scientific discipline stemmed from the work of Gregor Mendel in the middle of the 19th century. Mendel suspected that traits were inherited as discrete units, and, although he knew nothing of the physical or chemical nature of genes at the time, his units became the basis for the development of the present understanding of heredity. All present research in genetics can be traced back to Mendels discovery of the laws governing the inheritance of traits. The word genetics was introduced in 1905 by English biologist William Bateson, who was one of the discoverers of Mendels work and who became a champion of Mendels principles of inheritance.

Although scientific evidence for patterns of genetic inheritance did not appear until Mendels work, history shows that humankind must have been interested in heredity long before the dawn of civilization. Curiosity must first have been based on human family resemblances, such as similarity in body structure, voice, gait, and gestures. Such notions were instrumental in the establishment of family and royal dynasties. Early nomadic tribes were interested in the qualities of the animals that they herded and domesticated and, undoubtedly, bred selectively. The first human settlements that practiced farming appear to have selected crop plants with favourable qualities. Ancient tomb paintings show racehorse breeding pedigrees containing clear depictions of the inheritance of several distinct physical traits in the horses. Despite this interest, the first recorded speculations on heredity did not exist until the time of the ancient Greeks; some aspects of their ideas are still considered relevant today.

Hippocrates (c. 460c. 375 bce), known as the father of medicine, believed in the inheritance of acquired characteristics, and, to account for this, he devised the hypothesis known as pangenesis. He postulated that all organs of the body of a parent gave off invisible seeds, which were like miniaturized building components and were transmitted during sexual intercourse, reassembling themselves in the mothers womb to form a baby.

Aristotle (384322 bce) emphasized the importance of blood in heredity. He thought that the blood supplied generative material for building all parts of the adult body, and he reasoned that blood was the basis for passing on this generative power to the next generation. In fact, he believed that the males semen was purified blood and that a womans menstrual blood was her equivalent of semen. These male and female contributions united in the womb to produce a baby. The blood contained some type of hereditary essences, but he believed that the baby would develop under the influence of these essences, rather than being built from the essences themselves.

Aristotles ideas about the role of blood in procreation were probably the origin of the still prevalent notion that somehow the blood is involved in heredity. Today people still speak of certain traits as being in the blood and of blood lines and blood ties. The Greek model of inheritance, in which a teeming multitude of substances was invoked, differed from that of the Mendelian model. Mendels idea was that distinct differences between individuals are determined by differences in single yet powerful hereditary factors. These single hereditary factors were identified as genes. Copies of genes are transmitted through sperm and egg and guide the development of the offspring. Genes are also responsible for reproducing the distinct features of both parents that are visible in their children.

In the two millennia between the lives of Aristotle and Mendel, few new ideas were recorded on the nature of heredity. In the 17th and 18th centuries the idea of preformation was introduced. Scientists using the newly developed microscopes imagined that they could see miniature replicas of human beings inside sperm heads. French biologist Jean-Baptiste Lamarck invoked the idea of the inheritance of acquired characters, not as an explanation for heredity but as a model for evolution. He lived at a time when the fixity of species was taken for granted, yet he maintained that this fixity was only found in a constant environment. He enunciated the law of use and disuse, which states that when certain organs become specially developed as a result of some environmental need, then that state of development is hereditary and can be passed on to progeny. He believed that in this way, over many generations, giraffes could arise from deerlike animals that had to keep stretching their necks to reach high leaves on trees.

British naturalist Alfred Russel Wallace originally postulated the theory of evolution by natural selection. However, Charles Darwins observations during his circumnavigation of the globe aboard the HMS Beagle (183136) provided evidence for natural selection and his suggestion that humans and animals shared a common ancestry. Many scientists at the time believed in a hereditary mechanism that was a version of the ancient Greek idea of pangenesis, and Darwins ideas did not appear to fit with the theory of heredity that sprang from the experiments of Mendel.

Before Gregor Mendel, theories for a hereditary mechanism were based largely on logic and speculation, not on experimentation. In his monastery garden, Mendel carried out a large number of cross-pollination experiments between variants of the garden pea, which he obtained as pure-breeding lines. He crossed peas with yellow seeds to those with green seeds and observed that the progeny seeds (the first generation, F1) were all yellow. When the F1 individuals were self-pollinated or crossed among themselves, their progeny (F2) showed a ratio of 3:1 (3/4 yellow and 1/4 green). He deduced that, since the F2 generation contained some green individuals, the determinants of greenness must have been present in the F1 generation, although they were not expressed because yellow is dominant over green. From the precise mathematical 3:1 ratio (of which he found several other examples), he deduced not only the existence of discrete hereditary units (genes) but also that the units were present in pairs in the pea plant and that the pairs separated during gamete formation. Hence, the two original lines of pea plants were proposed to be YY (yellow) and yy (green). The gametes from these were Y and y, thereby producing an F1 generation of Yy that were yellow in colour because of the dominance of Y. In the F1 generation, half the gametes were Y and the other half were y, making the F2 generation produced from random mating 1/4 Yy, 1/2 YY, and 1/4 yy, thus explaining the 3:1 ratio. The forms of the pea colour genes, Y and y, are called alleles.

Mendel also analyzed pure lines that differed in pairs of characters, such as seed colour (yellow versus green) and seed shape (round versus wrinkled). The cross of yellow round seeds with green wrinkled seeds resulted in an F1 generation that were all yellow and round, revealing the dominance of the yellow and round traits. However, the F2 generation produced by self-pollination of F1 plants showed a ratio of 9:3:3:1 (9/16 yellow round, 3/16 yellow wrinkled, 3/16 green round, and 1/16 green wrinkled; note that a 9:3:3:1 ratio is simply two 3:1 ratios combined). From this result and others like it, he deduced the independent assortment of separate gene pairs at gamete formation.

Mendels success can be attributed in part to his classic experimental approach. He chose his experimental organism well and performed many controlled experiments to collect data. From his results, he developed brilliant explanatory hypotheses and went on to test these hypotheses experimentally. Mendels methodology established a prototype for genetics that is still used today for gene discovery and understanding the genetic properties of inheritance.

Mendels genes were only hypothetical entities, factors that could be inferred to exist in order to explain his results. The 20th century saw tremendous strides in the development of the understanding of the nature of genes and how they function. Mendels publications lay unmentioned in the research literature until 1900, when the same conclusions were reached by several other investigators. Then there followed hundreds of papers showing Mendelian inheritance in a wide array of plants and animals, including humans. It seemed that Mendels ideas were of general validity. Many biologists noted that the inheritance of genes closely paralleled the inheritance of chromosomes during nuclear divisions, called meiosis, that occur in the cell divisions just prior to gamete formation.

heredity: sex-linked inheritance in Drosophila fliesEncyclopdia Britannica, Inc.It seemed that genes were parts of chromosomes. In 1910 this idea was strengthened through the demonstration of parallel inheritance of certain Drosophila (a type of fruit fly) genes on sex-determining chromosomes by American zoologist and geneticist Thomas Hunt Morgan. Morgan and one of his students, Alfred Henry Sturtevant, showed not only that certain genes seemed to be linked on the same chromosome but that the distance between genes on the same chromosome could be calculated by measuring the frequency at which new chromosomal combinations arose (these were proposed to be caused by chromosomal breakage and reunion, also known as crossing over). In 1916 another student of Morgans, Calvin Bridges, used fruit flies with an extra chromosome to prove beyond reasonable doubt that the only way to explain the abnormal inheritance of certain genes was if they were part of the extra chromosome. American geneticist Hermann Joseph Mller showed that new alleles (called mutations) could be produced at high frequencies by treating cells with X-rays, the first demonstration of an environmental mutagenic agent (mutations can also arise spontaneously). In 1931 American botanist Harriet Creighton and American scientist Barbara McClintock demonstrated that new allelic combinations of linked genes were correlated with physically exchanged chromosome parts.

In 1908 British physician Archibald Garrod proposed the important idea that the human disease alkaptonuria, and certain other hereditary diseases, were caused by inborn errors of metabolism, suggesting for the first time that linked genes had molecular action at the cell level. Molecular genetics did not begin in earnest until 1941 when American geneticist George Beadle and American biochemist Edward Tatum showed that the genes they were studying in the fungus Neurospora crassa acted by coding for catalytic proteins called enzymes. Subsequent studies in other organisms extended this idea to show that genes generally code for proteins. Soon afterward, American bacteriologist Oswald Avery, Canadian American geneticist Colin M. MacLeod, and American biologist Maclyn McCarty showed that bacterial genes are made of DNA, a finding that was later extended to all organisms.

DNAEncyclopdia Britannica, Inc.A major landmark was attained in 1953 when American geneticist and biophysicist James D. Watson and British biophysicists Francis Crick and Maurice Wilkins devised a double helix model for DNA structure. This model showed that DNA was capable of self-replication by separating its complementary strands and using them as templates for the synthesis of new DNA molecules. Each of the intertwined strands of DNA was proposed to be a chain of chemical groups called nucleotides, of which there were known to be four types. Because proteins are strings of amino acids, it was proposed that a specific nucleotide sequence of DNA could contain a code for an amino acid sequence and hence protein structure. In 1955 American molecular biologist Seymour Benzer, extending earlier studies in Drosophila, showed that the mutant sites within a gene could be mapped in relation to each other. His linear map indicated that the gene itself is a linear structure.

In 1958 the strand-separation method for DNA replication (called the semiconservative method) was demonstrated experimentally for the first time by American molecular biologist Matthew Meselson and American geneticist Franklin W. Stahl. In 1961 Crick and South African biologist Sydney Brenner showed that the genetic code must be read in triplets of nucleotides, called codons. American geneticist Charles Yanofsky showed that the positions of mutant sites within a gene matched perfectly the positions of altered amino acids in the amino acid sequence of the corresponding protein. In 1966 the complete genetic code of all 64 possible triplet coding units (codons), and the specific amino acids they code for, was deduced by American biochemists Marshall Nirenberg and Har Gobind Khorana. Subsequent studies in many organisms showed that the double helical structure of DNA, the mode of its replication, and the genetic code are the same in virtually all organisms, including plants, animals, fungi, bacteria, and viruses. In 1961 French biologist Franois Jacob and French biochemist Jacques Monod established the prototypical model for gene regulation by showing that bacterial genes can be turned on (initiating transcription into RNA and protein synthesis) and off through the binding action of regulatory proteins to a region just upstream of the coding region of the gene.

Technical advances have played an important role in the advance of genetic understanding. In 1970 American microbiologists Daniel Nathans and Hamilton Othanel Smith discovered a specialized class of enzymes (called restriction enzymes) that cut DNA at specific nucleotide target sequences. That discovery allowed American biochemist Paul Berg in 1972 to make the first artificial recombinant DNA molecule by isolating DNA molecules from different sources, cutting them, and joining them together in a test tube. These advances allowed individual genes to be cloned (amplified to a high copy number) by splicing them into self-replicating DNA molecules, such as plasmids (extragenomic circular DNA elements) or viruses, and inserting these into living bacterial cells. From these methodologies arose the field of recombinant DNA technology that presently dominates molecular genetics. In 1977 two different methods were invented for determining the nucleotide sequence of DNA: one by American molecular biologists Allan Maxam and Walter Gilbert and the other by English biochemist Fred Sanger. Such technologies made it possible to examine the structure of genes directly by nucleotide sequencing, resulting in the confirmation of many of the inferences about genes originally made indirectly.

DNA fingerprinting: polymerase chain reactionEncyclopdia Britannica, Inc.In the 1970s Canadian biochemist Michael Smith revolutionized the art of redesigning genes by devising a method for inducing specifically tailored mutations at defined sites within a gene, creating a technique known as site-directed mutagenesis. In 1983 American biochemist Kary B. Mullis invented the polymerase chain reaction, a method for rapidly detecting and amplifying a specific DNA sequence without cloning it. In the last decade of the 20th century, progress in recombinant DNA technology and in the development of automated sequencing machines led to the elucidation of complete DNA sequences of several viruses, bacteria, plants, and animals. In 2001 the complete sequence of human DNA, approximately three billion nucleotide pairs, was made public.

A time line of important milestones in the history of genetics is provided in the table.

Time line of important milestones in the history of genetics

Classical genetics, which remains the foundation for all other areas in genetics, is concerned primarily with the method by which genetic traitsclassified as dominant (always expressed), recessive (subordinate to a dominant trait), intermediate (partially expressed), or polygenic (due to multiple genes)are transmitted in plants and animals. These traits may be sex-linked (resulting from the action of a gene on the sex, or X, chromosome) or autosomal (resulting from the action of a gene on a chromosome other than a sex chromosome). Classical genetics began with Mendels study of inheritance in garden peas and continues with studies of inheritance in many different plants and animals. Today a prime reason for performing classical genetics is for gene discoverythe finding and assembling of a set of genes that affects a biological property of interest.

Cytogenetics, the microscopic study of chromosomes, blends the skills of cytologists, who study the structure and activities of cells, with those of geneticists, who study genes. Cytologists discovered chromosomes and the way in which they duplicate and separate during cell division at about the same time that geneticists began to understand the behaviour of genes at the cellular level. The close correlation between the two disciplines led to their combination.

Plant cytogenetics early became an important subdivision of cytogenetics because, as a general rule, plant chromosomes are larger than those of animals. Animal cytogenetics became important after the development of the so-called squash technique, in which entire cells are pressed flat on a piece of glass and observed through a microscope; the human chromosomes were numbered using this technique.

Today there are multiple ways to attach molecular labels to specific genes and chromosomes, as well as to specific RNAs and proteins, that make these molecules easily discernible from other components of cells, thereby greatly facilitating cytogenetics research.

Microorganisms were generally ignored by the early geneticists because they are small in size and were thought to lack variable traits and the sexual reproduction necessary for a mixing of genes from different organisms. After it was discovered that microorganisms have many different physical and physiological characteristics that are amenable to study, they became objects of great interest to geneticists because of their small size and the fact that they reproduce much more rapidly than larger organisms. Bacteria became important model organisms in genetic analysis, and many discoveries of general interest in genetics arose from their study. Bacterial genetics is the centre of cloning technology.

Viral genetics is another key part of microbial genetics. The genetics of viruses that attack bacteria were the first to be elucidated. Since then, studies and findings of viral genetics have been applied to viruses pathogenic on plants and animals, including humans. Viruses are also used as vectors (agents that carry and introduce modified genetic material into an organism) in DNA technology.

Molecular genetics is the study of the molecular structure of DNA, its cellular activities (including its replication), and its influence in determining the overall makeup of an organism. Molecular genetics relies heavily on genetic engineering (recombinant DNA technology), which can be used to modify organisms by adding foreign DNA, thereby forming transgenic organisms. Since the early 1980s, these techniques have been used extensively in basic biological research and are also fundamental to the biotechnology industry, which is devoted to the manufacture of agricultural and medical products. Transgenesis forms the basis of gene therapy, the attempt to cure genetic disease by addition of normally functioning genes from exogenous sources.

The development of the technology to sequence the DNA of whole genomes on a routine basis has given rise to the discipline of genomics, which dominates genetics research today. Genomics is the study of the structure, function, and evolutionary comparison of whole genomes. Genomics has made it possible to study gene function at a broader level, revealing sets of genes that interact to impinge on some biological property of interest to the researcher. Bioinformatics is the computer-based discipline that deals with the analysis of such large sets of biological information, especially as it applies to genomic information.

The study of genes in populations of animals, plants, and microbes provides information on past migrations, evolutionary relationships and extents of mixing among different varieties and species, and methods of adaptation to the environment. Statistical methods are used to analyze gene distributions and chromosomal variations in populations.

Population genetics is based on the mathematics of the frequencies of alleles and of genetic types in populations. For example, the Hardy-Weinberg formula, p2 + 2pq + q2 = 1, predicts the frequency of individuals with the respective homozygous dominant (AA), heterozygous (Aa), and homozygous recessive (aa) genotypes in a randomly mating population. Selection, mutation, and random changes can be incorporated into such mathematical models to explain and predict the course of evolutionary change at the population level. These methods can be used on alleles of known phenotypic effect, such as the recessive allele for albinism, or on DNA segments of any type of known or unknown function.

Human population geneticists have traced the origins and migration and invasion routes of modern humans, Homo sapiens. DNA comparisons between the present peoples on the planet have pointed to an African origin of Homo sapiens. Tracing specific forms of genes has allowed geneticists to deduce probable migration routes out of Africa to the areas colonized today. Similar studies show to what degree present populations have been mixed by recent patterns of travel.

Another aspect of genetics is the study of the influence of heredity on behaviour. Many aspects of animal behaviour are genetically determined and can therefore be treated as similar to other biological properties. This is the subject material of behaviour genetics, whose goal is to determine which genes control various aspects of behaviour in animals. Human behaviour is difficult to analyze because of the powerful effects of environmental factors, such as culture. Few cases of genetic determination of complex human behaviour are known. Genomics studies provide a useful way to explore the genetic factors involved in complex human traits such as behaviour.

Some geneticists specialize in the hereditary processes of human genetics. Most of the emphasis is on understanding and treating genetic disease and genetically influenced ill health, areas collectively known as medical genetics. One broad area of activity is laboratory research dealing with the mechanisms of human gene function and malfunction and investigating pharmaceutical and other types of treatments. Since there is a high degree of evolutionary conservation between organisms, research on model organismssuch as bacteria, fungi, and fruit flies (Drosophila)which are easier to study, often provides important insights into human gene function.

Many single-gene diseases, caused by mutant alleles of a single gene, have been discovered. Two well-characterized single-gene diseases include phenylketonuria (PKU) and Tay-Sachs disease. Other diseases, such as heart disease, schizophrenia, and depression, are thought to have more complex heredity components that involve a number of different genes. These diseases are the focus of a great deal of research that is being carried out today.

Another broad area of activity is clinical genetics, which centres on advising parents of the likelihood of their children being affected by genetic disease caused by mutant genes and abnormal chromosome structure and number. Such genetic counseling is based on examining individual and family medical records and on diagnostic procedures that can detect unexpressed, abnormal forms of genes. Counseling is carried out by physicians with a particular interest in this area or by specially trained nonphysicians.

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Research News: New Skin Stem Cells Surprisingly Similar to …

Scientists have discovered a new type of stem cell in the skin that acts surprisingly like certain stem cells found in embryos: both can generate fat, bone, cartilage, and even nerve cells. These newly-described dermal stem cells may one day prove useful for treating neurological disorders and persistent wounds, such as diabetic ulcers, says Freda Miller, an HHMI international research scholar.

Miller and her colleagues first saw the cells several years ago in both rodents and people, but only now confirmed that the cells are stem cells. Like other stem cells, these cell scan self-renew and, under the right conditions, they can grow into the cell types that constitute the skins dermal layer, which lies under the surface epidermal layer. We showed that these cells are, in fact, the real thing, says Miller, a professor at the University of Toronto and a senior scientist in the department of developmental biology at the Hospital for Sick Children in Toronto. The dermal stem cells also appear tohelp form the basis for hair growth.The new work was published December 4, 2009, in the journal Cell Stem Cells.

Stem cell researchers like to talk about building organs in a dish. You can imagine, if you have all the right playersdermal stem cells and epidermal stem cellsworking together, you could do that with skin in a very real way.

Freda D. Miller

Though this research focuses on the skin, Miller has spent her career searching for cures for neurological diseases such as Parkinsons. About a decade ago, she decided to find an easily accessible cell that could be coaxed into making nerves. Brain stem cells, some of which can grow into nerves, lie deep in the middle of the organ and are too difficult to reach if the scientists eventually wanted to cultivate the cells from individual patients. I thought, This is blue sky stuff, but you never know. She searched the literature and found that amphibians can regenerate nerves in their skin. She also found published hints that mammalian nerve cells could do the same.

Her team looked in the dermal layer of the skin in both mice and people. Hair follicles and sweat glands are rooted in the dermis, a thick layer of cells that also help support and nourish blood vessels and touch-perceiving nerves. In 2001, Millers team hit paydirt when they discovered cells that respond to the same growth factors that make brain stem cells differentiate. She named them skin-derived precursors (SKPs, or skips).

Miller soon discovered that the cells act like neural crest cells from embryosstem cells that generate the entire peripheral nervous system and part of the headin that they could turn into nerves, fat, bone, and cartilage.That gave us the idea that these were some kind of embryonic-like precursor cell that migrated into the skin of the embryo, Miller said. But instead of disappearing as the embryo develops, the cells survive into adulthood.

Even though the SKPs acted like stem cells in Petri dishes, Miller didnt know if they behaved the same way in the body. We were obviously very excited about these cells, she said. The problem was, cells can do all kinds of weird things in culture dishes that look right but really arent. We thought, Maybe were being deceived.So lab member Jeffrey Biernaskie put the cells through their paces, performing a series of experiments to test whether the SKPs indeed acted like stem cells in the body.

Earlier work in the lab had shown that the SKPs produce a transcription factor called SOX2, which is produced in many types of stem cells. The team used genetically engineered mice with SOX2 genes tagged with green fluorescent protein, which allowed them to track where SOX2 was expressed in the animals. They found that about 1% of skin cells from adult mice contained the SOX2-making cells, and they were concentrated in the bulb at the base of hair follicles.When the team cultured these cells, they began behaving like SKPs.

Next, the scientists decided to see if the cells would not just settle at the base of hair follicles but grow new hair. They took the fluorescent cells, mixed them with epidermal cellswhich make up the majority of cells in a hair follicleand transplanted the mixture under the skin of hairless mice. These mice began growing hair, and analysis showed the green cells migrated to their home base in the bulb of the new hair follicles. The team also transplanted rat SKP cells under the skin of mice. The cells behaved exactly like dermal stem cellsthey spread out through the dermis and differentiated into various dermal cell types, including fat cells and dermal fibroblasts, which form the structural framework of the dermal layer. Intriguingly, the mice that carried transplanted rat SKPs also grew longer, thicker,rat-like hair, instead of short, thin mouse hair. These cells are instructive, they tell the epidermal cellswhich form the bulk of the hair follicleto make bigger, rat-like hair follicles, Miller said. There are a lot of jokes in my lab about bald men running around with rat hair on their heads.

Finally, the team gave mice small puncture wounds and then transplanted their fluorescent SKPs next to the wound. Within a month, many transplanted cells appeared in the scar, showing they had contributed to wound healing. The SKPs were also found in new hair follicles in the healed skin.

The cells behavior both in wound healing and hair growth led the team to conclude that the SKPs are, in fact, dermal stem cells. Miller said the finding complements work by HHMI investigator Elaine Fuchs, who found epidermal stem cells, which help renew the top layer of skin. Combining the evidence from the two labs suggests a possible path to baldness treatments, Miller saidthe dermal stem cells at the base of the hair follicle seem to be signaling the epidermal cells that form the shaft of the follicle to grow hair. But much about the signaling mechanism remains unknown.

Miller wants to investigate less cosmetic applications, such as treating nerve and brain diseases. Experiments she published between 2005 and 2007 showed that SKPs can grow into nerves and help repair spinal cord damage in rats. Her lab is continuing to pursue that research. She is also searching for signals that could trigger the dermal stem cells to rev up their innate wound-healing ability. If such a signal can be found and mimicked, Miller can envision one day treating chronic woundssuch as diabetic ulcerswith a topical cream. Such a treatment is years or decades away, she said, but now researchers know which cell types to focus on. Another possibility: improving skin grafts, which today consist of only epidermal, not dermal, cells. While skin grafts can dramatically help burn victims, those grafts dont function like normal skin.

Stem cell researchers like to talk about building organs in a dish, said Miller. You can imagine, if you have all the right playersdermal stem cells and epidermal stem cellsworking together, you could do that with skin in a very real way.

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Research News: New Skin Stem Cells Surprisingly Similar to …

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Skin Regeneration with Stem Cells, Growth Factors …

At a Glance

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Our skin is an extremely important and multi-faceted organ. It protects our insides by providing a cover for our body and is responsible for preventing pathogens entering our organism. The skin also fulfills other important roles by regulating body temperature, in the area of metabolism, and for our sensitivity to touch and stimuli.

In addition, our skin also contains a large quantity of autologous stem cells (so-called adult stem cells). Autologous stem cells are on the one hand relevant for the external appearance of the skin, and on the other hand they offer a great deal of positive therapeutic potential in the area of regenerative medicine.

If we bear in mind what kind of functions our skin has, it becomes obvious why we should be paying special attention to its health.

Already in the traditional European medicine there was the tenet As inside, so outside. Even in modern science we know that it is important to distinguish between cause and effect and that many degenerative processes inside the body manifest externally.

For example, various factors can lead to a massive acceleration of the per se normal skin aging: Stress, overload and unhealthy diet can cause hormonal dysfunction, which in turn leads to premature aging and tissue slackening. Certain lifestyle habits such as tanning booths as well as smoking can cause skin damages over time, which can often make people concerned look more than 10 years older than they actually are.

Our therapeutic approach is not only to treat the symptom (= premature aging of the skin), but the cause (= e.g., hormone deficiency) as far as possible. Combinations of both the therapy of the cause and targeted local treatments can be useful, especially when a large distress is present and/or the skin damages are very advanced.

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We use the autologous substances for our skin treatments. We never use artificial fillers (e.g., silicone) or Botox, because their side effects often lead to a worsening of skin quality.

When we are young, the body still has enough stem cells and produces sufficient growth factors and hormones, however, as the years pass, the body produces less of them. This wear process can be accelerated by stress, overwork, poor nutrition and certain lifestyle habits. The external signs of premature aging appear, such as wrinkles, slackening of tissue, sagging cheeks and greying of the skin.

All types of treatment offered by our clinic serve the purpose of giving your skin back a certain amount of quality, elasticity and freshness by targeted application of the autologous substances or substances similar to the bodys own.

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A Safeguard System for Induced Pluripotent Stem Cell …


iPSC-derived rejuvenated CTLs are effective against EBV-induced tumors invivo

Rejuvenated CTLs are implemented with an inducible caspase-9 (iC9)-based suicide system

Upon induction, the iC9 system efficiently leads to apoptosis in rejuvenated CTLs

The iC9-based system provides a safeguard for future iPSC-mediated cell therapy

The discovery of induced pluripotent stem cells (iPSCs) has created promising new avenues for therapies in regenerative medicine. However, the tumorigenic potential of undifferentiated iPSCs is a major safety concern for clinical translation. To address this issue, we demonstrated the efficacy of suicide gene therapy by introducing inducible caspase-9 (iC9) into iPSCs. Activation of iC9 with a specific chemical inducer of dimerization (CID) initiates a caspase cascade that eliminates iPSCs and tumors originated from iPSCs. We introduced this iC9/CID safeguard system into a previously reported iPSC-derived, rejuvenated cytotoxic T lymphocyte (rejCTL) therapy model and confirmed that we can generate rejCTLs from iPSCs expressing high levels of iC9 without disturbing antigen-specific killingactivity. iC9-expressing rejCTLs exert antitumor effects invivo. The system efficiently and safely induces apoptosis in these rejCTLs. These results unite to suggest that the iC9/CID safeguard system is a promising tool for future iPSC-mediated approaches to clinical therapy.

Human induced pluripotent stem cells (iPSCs) can unlimitedly self-renew and differentiate into various cell types (Takahashi etal., 2007). Their pluripotency makes iPSCs a promising tool for therapy in a wide range of diseases at present refractory to treatment (Inoue etal., 2014). Recent studies, however, reported the tumorigenic potential of contaminated undifferentiated iPSCs and the malignant transformation of differentiated iPSCs (Lee etal., 2013aandNori etal., 2015). The tumorigenic risks of iPSCs could be reduced by several strategies, such as sorting out undifferentiated cells with antibodies targeting surface-displayed biomarkers (Tang etal., 2011), killing undifferentiated cells with cytotoxic antibodies (Choo etal., 2008), or elimination of remaining undifferentiated pluripotent cells with chemical inhibitors (Ben-David etal., 2013andLee etal., 2013b). However, these strategies may not suffice to lower risk to acceptable levels, because the tumorigenic risk of iPSC-based cell therapy arises not just from contamination with undifferentiated iPSCs but also from other unexpected events associated with long-term culture for reprogramming and redifferentiation. There is always a chance of unexpected issues associated with first-in-human clinical studies.

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A Safeguard System for Induced Pluripotent Stem Cell …

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Research and Markets: Global Cell Therapy Technologies …

DUBLIN–(BUSINESS WIRE)–Research and Markets ( has announced the addition of Jain PharmaBiotech’s new report “Cell Therapy – Technologies, Markets and Companies” to their offering.

This report describes and evaluates cell therapy technologies and methods, which have already started to play an important role in the practice of medicine. Hematopoietic stem cell transplantation is replacing the old fashioned bone marrow transplants. Role of cells in drug discovery is also described. Cell therapy is bound to become a part of medical practice.

The number of companies involved in cell therapy has increased remarkably during the past few years. More than 500 companies have been identified to be involved in cell therapy and 296 of these are profiled in part II of the report along with tabulation of 280 alliances. Of these companies, 167 are involved in stem cells. Profiles of 72 academic institutions in the US involved in cell therapy are also included in part II along with their commercial collaborations. The text is supplemented with 62 Tables and 17 Figures. The bibliography contains 1,200 selected references, which are cited in the text.

Stem cells are discussed in detail in one chapter. Some light is thrown on the current controversy of embryonic sources of stem cells and comparison with adult sources. Other sources of stem cells such as the placenta, cord blood and fat removed by liposuction are also discussed. Stem cells can also be genetically modified prior to transplantation.

Cell therapy technologies overlap with those of gene therapy, cancer vaccines, drug delivery, tissue engineering and regenerative medicine. Pharmaceutical applications of stem cells including those in drug discovery are also described. Various types of cells used, methods of preparation and culture, encapsulation and genetic engineering of cells are discussed. Sources of cells, both human and animal (xenotransplantation) are discussed. Methods of delivery of cell therapy range from injections to surgical implantation using special devices.

Cell therapy has applications in a large number of disorders. The most important are diseases of the nervous system and cancer which are the topics for separate chapters. Other applications include cardiac disorders (myocardial infarction and heart failure), diabetes mellitus, diseases of bones and joints, genetic disorders, and wounds of the skin and soft tissues.

Regulatory and ethical issues involving cell therapy are important and are discussed. Current political debate on the use of stem cells from embryonic sources (hESCs) is also presented. Safety is an essential consideration of any new therapy and regulations for cell therapy are those for biological preparations.

The cell-based markets was analyzed for 2014, and projected to 2024.The markets are analyzed according to therapeutic categories, technologies and geographical areas. The largest expansion will be in diseases of the central nervous system, cancer and cardiovascular disorders. Skin and soft tissue repair as well as diabetes mellitus will be other major markets.

Key Topics Covered:

Part I: Technologies, Ethics & Regulations

0. Executive Summary

1. Introduction to Cell Therapy

2. Cell Therapy Technologies

3. Stem Cells

4. Clinical Applications of Cell Therapy

5. Cell Therapy for Cancer

6. Cell Therapy for Neurological Disorders

7. Ethical, Legal and Political Aspects of Cell therapy

8. Safety and Regulatory Aspects of Cell Therapy

Part II: Markets, Companies & Academic Institutions

9. Markets and Future Prospects for Cell Therapy

10. Companies Involved in Cell Therapy

11. Academic Institutions

12. References

For more information visit

Source: Jain PharmaBiotech

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Going viral: chimeric antigen receptor T-cell therapy for …

On July 1, 2014, the United States Food and Drug Administration granted ‘breakthrough therapy’ designation to CTL019, the anti-CD19 chimeric antigen receptor T-cell therapy developed at the University of Pennsylvania. This is the first personalized cellular therapy for cancer to be so designated and occurred 25 years after the first publication describing genetic redirection of T cells to a surface antigen of choice. The peer-reviewed literature currently contains the outcomes of more than 100 patients treated on clinical trials of anti-CD19 redirected T cells, and preliminary results on many more patients have been presented. At last count almost 30 clinical trials targeting CD19 were actively recruiting patients in North America, Europe, and Asia. Patients with high-risk B-cell malignancies therefore represent the first beneficiaries of an exciting and potent new treatment modality that harnesses the power of the immune system as never before. A handful of trials are targeting non-CD19 hematological and solid malignancies and represent the vanguard of enormous preclinical efforts to develop CAR T-cell therapy beyond B-cell malignancies. In this review, we explain the concept of chimeric antigen receptor gene-modified T cells, describe the extant results in hematologic malignancies, and share our outlook on where this modality is likely to head in the near future.

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Going viral: chimeric antigen receptor T-cell therapy for …

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Stem Cell Therapy – Premier Stem Cell Institute

Formerly Orthopedic Stem Cell Institute We put the power of your own body to work for you.

Our team of board certified, fellowship-trained orthopedic and spine surgeons work with patients from around the world using the newest and most advanced technology to treat orthopedic injuries and bone and joint pain, as well as relieving symptoms and improving the lives of patients with a multitude of illnesses.

The Premier Stem Cell Institute is a leading research and treatment facility in Colorado providing the most innovative and proven techniques and therapies using the bodys natural healing power of stem cells.

A stem cell is a basic cell constantly produced by your body to heal injuries, build new skin, even grow your hair. However, your body wont refix a chronic injury or illness by continuing to attack it with new stem cells unless those cells are extracted and reintroduced into your body via stem cell therapies.

We are a leading research and treatment facility providing the most innovative and proven techniques and therapies using the bodys natural healing power of stem cells. Our services are performed by fellowship-trained surgeons using the most state-of-the-art equipment and technology in the field.All stem cell treatments are not alike. AtPremier Stem Cell Institute, we extract your stem cells from your bone marrow because they are higher quality and result in better outcomes than stem cells from fat (adipose). We treat each patient with the utmost respect and our concierge service makes you feel incredibly well cared for from the first phone call to follow up visits.

They’re very personable, they’re very helpful..nice people. Bottom line is there’s no pain where there was a lot of pain before.

Jon Hoffman, Former NFL Player

I used to dread doing simple things like putting on a coat, a seat belt or reaching for things. I can now do those things without nearly as much difficulty. I want to thank everyone at the clinic for performing the procedure on me. They are making peoples’ lives much more enjoyable.

Bob Hyland, Former NFL Player

It’s amazing! You’re awake the whole time, it’s virtually painless, and within an hour you’re walking out.

Don Horn, Former NFL Player

of Patients are 70% Better Within 1 Year!

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Stem Cell Therapy – Premier Stem Cell Institute

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Cure For Blindness? Stem Cell Therapy Offers Hope

A cure for blindness in patients with age-related macular degeneration may be on the horizon. Doctors with the London Project to Cure Blindness confirmed 10 patients will undergo an experimental procedure that could slow or reverse the debilitating condition.

Age-related macular degeneration is a common, but devastating, condition affecting the vision of adults over the age of 50.

As explained by the National Eye Institute, AMD causes damage to a portion of the retina called the macula. Located in the rear portion of the eye, the macula is the most sensitive part of the eye.

Although the condition progresses slowly in most patients, the onset can be more aggressive for some.

Patients with AMD initially experience blurred or distorted sight in the center of vision, as the macula is located in the center of the retina. As the condition progresses, patients may experience worsening loss of vision in one or both eyes.

Although AMD does not cause total loss of vision, the loss of central vision in AMD can interfere with simple everyday activities, such as the ability to see faces, drive, read, write, or do close work.

As there is no cure for blindness, advanced stages of the condition can be devastating. According to the National Eye Institute, anyone can develop age-related macular degeneration. However, risk factors may include family history and smoking.

AMD treatment options vary depending on the stage of progression when diagnosed. Although early AMD can be detected by an eye care professional, there are no current treatment options for early AMD. Intermediate and late AMD can be treated with vitamin supplements. However, the effectiveness of this treatment is unclear.

Advanced neovascular AMD can be treated with ocular injections, laser treatment, and laser surgery. Although these treatment options may help treat the condition, there is no absolute cure for blindness caused by AMD.

As reported by the Express, scientists in the UK are currently exploring an experimental treatment, which uses embryonic stem cells to replace the damaged macula.

Essentially, embroyonic stem cells are being used to grow patches of new cells that are transplanted onto the eye. According to the doctors, the stem cells were harvested from donated embryos that were created during IVF treatment but never used.

If the procedure works as planned, the doctors may have discovered a cure for blindness in patients with AMD.

The first of 10 experimental procedures was performed in recent weeks on an unnamed 60-year-old woman. It is unclear whether the procedure slowed or reversed the patients AMD, as it may take several months to heal. However, doctors said the woman has not experienced any unforeseen complications.

In the next year and a half, nine more patients will undergo the experimental procedure. All then patients, including the 60-year-old woman, were diagnosed with advanced age-related macular degeneration.

In the UK alone, an estimated 600,000 people suffer with some form of AMD. Essentially, one in every 10 people over 65 has some degree of AMD.

Although there is no current cure for blindness, the experimental treatment offers hope for patients who have suffered a devastating loss of vision.

As reported by BBC News, the doctors hope the procedure will improve the patients quality of life.

Prof. Lyndon Da Cruz of Moorfields Eye Hospital, who performed the surgery on the 60-year-old woman, said the treatment may also be effective in treating patients with earlier stages of the devastating condition.

The London Project to Cure Blindness research is being funded by pharmaceutical company Pfizer. Although it is unclear whether the procedure will prove to be a cure for blindness, the doctors are confident that they will have positive results.

[Image via Shutterstock]

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Cure For Blindness? Stem Cell Therapy Offers Hope

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First UK patient receives stem cell treatment to cure loss …

A patient has become the first in the UK to receive an experimental stem cell treatment that has the potential to save the sight of hundreds of thousands of Britons.

By December, doctors will know whether the woman, who has age-related macular degeneration, has regained her sight after a successful operation at Moorfields Eye Hospital in London last month. Over 18 months, 10 patients will undergo the treatment.

The transplant involves eye cells, called retinal pigment epithelium, derived from stem cells and grown in the lab to form a patch that can be placed behind the retina during surgery.

Related: Stem cell therapy success in treatment of sight loss from macular degeneration

The potential is huge. Although the first patients have the wet form of macular degeneration, the doctors believe it might also eventually work for those who have the dry form, who are the vast majority of the UKs 700,000 sufferers.

The surgery is an exciting moment for the 10-year-old London Project to Cure Blindness, a collaboration between the hospital, the UCL Institute of Ophthalmology and the National Institute for Health Research, which was formed to find a cure for wet age-related macular degeneration, the more serious but less common form of the disease.

Prof Pete Coffey of UCL, one of the founders of the London Project, said he would not be working on the new treatment if he did not believe it would work. He hopes it could become a routine procedure for people afflicted by vision loss, which is as common a problem among older people as dementia.

It does involve an operation, but were trying to make it as straightforward as a cataract operation, he said. It will probably take 45 minutes to an hour. We could treat a substantial number of those patients.

First they have to get approval. The trial is not just about safety, but also efficacy. There will be a regulatory review after the first few transplants to ensure all is going well.

The group of patients chosen have the wet form of the disease and experienced sudden loss of vision within about six weeks. The support cells in the eye, which get rid of daily debris and allow the seeing part to function have died.

There is a possibility of restoring their vision, said Coffey. The aim of the transplant is to restore the support cells so the seeing part of the eye is not affected by what would become an increasingly toxic environment, causing deterioration and serious vision loss. The surgery is being performed by retinal surgeon Prof Lyndon Da Cruz from Moorfields, who is also a co-founder of the London Project.

The team chose people with this dramatic vision loss to see whether the experimental stem cell therapy would reverse the loss of vision. But in those with dry macular degeneration, said Coffey, the process is far slower, which would mean doctors could choose the time to intervene if the treatment works.

Helping people to regain their sight has long been one of the most hopeful prospects for stem cell transplantation. Other research groups have been trialling the use of stem cells in people with Stargardts disease, which destroys the vision at a much earlier age.

Stem cells have moved from the drawing board into human trials with incredible speed, scientists say. The first embryonic stem cell was derived in 1989. Using them in eyes was always going to have a big advantage over other prospects, because it is possible to transplant them without an all-out attack by the immune system, as would happen in other parts of the body. Most people who have any sort of transplant have to take drugs that suppress the immune system for the rest of their lives.

Just like conventional medicines, stem cell therapies will very likely have to be developed and marketed by large commercial concerns. The London Project has the US drug company Pfizer on board.

First UK patient receives stem cell treatment to cure loss …

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What are Hormones? – Hormone Replacement Therapy Denver

By Dr Dale Baird

Hormones are chemicals the body uses to direct our cells to perform various tasks. The tasks performed involve almost every function, from insulin production to brain intellectual development. They are in most abundance in our earlier years of life. When we are young, we dont really know how lucky we are to have fully functioning hormones. But at age 47-53 for most women, they start going away, its called in Menopause(for men its andropause). Symptoms of waxing and waning hormones are; weight gain, low or no energy, sleep disruption, no sexual desire, osteoporosis, heart disease, looking as if youre rapidly aging. There are many hormones (even Vit D is considered a hormone in some circumstances) but the main ones we usually deal with are the following; Estrogen, Testosterone, Progesterone, DHEA, Melatonin, and Cortisol. Both Estrogen and testosterone are derived from progesterone and DHEA. A healthy cholesterol level is important because all hormones are derived from it.

Estrogen is what makes a women different from a man, like wise Testosterone is what makes a man a man. Both of them are involved with the osteoporosis as is progesterone. All of these are very necessary for a healthy heart, brain, lungs, hormone system, digestive system.

As we age these hormones become less plentiful leading to the aging process. Hormone Replacement is the medical process of re-establishing normal known hormone levels. These levels are just about the same no matter what age you are! So when you use hormones to establish normal levels, we are essentially rolling back the clock, 20 to 30 years in most cases.

Hormone levels are dropping in younger age groups more than ever before. Our clinic sees the equivalent of a 70 year old levels with males and females in their mid twenties. More now than ever before, younger people are needing hormone replacement therapy (HRT).

HRT is not for everyone, some illnesses preclude hormones and hormone replacement. Call an HRT specialty Doctor to see if you need your hormones levels measured.

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What are Hormones? – Hormone Replacement Therapy Denver

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Research Summary: Research Finds Strong Genetic Diversity …

Genetic diversity in native switchgrass populations will benefit new varieties developed for biofuel production and ecosystem services.

Identification of gene pools and their geographic patterns will help in the development of new switchgrass varieties for biofuels, and for ecosystem services such as conservation and restoration. Identifying these gene pools relies on answering several questions: Where did the remnants of the genotypes originate? How much genetic diversity do they contain? Has there been transfer of genes between the genotypes?

Glaciation that covered much of the northern United States during the last ice age removed all vegetation and buried seeds under tons of silt and rock from a large portion of the country. When the glaciers retreated, plants returned to this region but with some distinct patterns.

Michael Casler, a research plant geneticist for the USDAs Agricultural Research Service and CenUSA collaborator, and his colleagues are developing a system of classifying gene pools of switchgrass that could provide germplasm for improvement of varieties for biofuels and ecosystems services.

For a bioenergy crop, high yields of biomass, which rely on traits such as height, tillering capability, persistence, and resistance to disease and insects, is the most important improvement they could provide. The desirability of other traits, such as efficient fermentation or high energy content, would depend on the intended final biofuel product.

Adaptability to marginal soils and conditions is also an important goal for improved varieties. A sustainable bioenergy production would not compete with food crops but would utilize land impractical for producing food for humans. Through DNA research, the researchers have identified the origins and the genetic diversity of the two switchgrass ecotypes, upland and lowland, in their native habitats. Because the two ecotypes are adapted to different environments, that identification is important in the classification of gene pools.

Crossing selected switchgrass plants in the field. Photo: Michael Casler, U.S. Dairy Forage Research Center.

In a related research project, Casler and his associates did DNA sequencing on 480 plants to look at possible gene flow between upland and lowland ecotypes.

Caslers research identified eight gene pools of switchgrass across the United States that could be a rich source of germplasm to improve commercial switchgrass varieties for biofuel, and in restoration and conservation work. These gene pools harbor a great deal of genetic variety, a potential source of new varieties that can respond better to climate change and improve germplasm.

As the climate gradually warmed after glaciation, what was left behind may have been a very close representation to what survives today hundreds to perhaps thousands of small, fragmented populations of switchgrass, representing a huge array of genetic and phenotypic diversity [2].

Research has turned up several other discoveries:

Research continues, using new genomic technologies to accelerate development of new varieties and genetically modified switchgrass, and to improve winter survival in southern types of switchgrass.

The strong diversity and wide adaptation of switchgrass is good news for those developing new commercial varieties of the perennial grass for bioenergy. Improved varieties would produce more biomass for biofuel production. Through adaptation to a single annual harvest, switchgrass will be more useful for commercial bioenergy production and harvest. If that harvest is delayed until after post-senescence dry-down, more nutrients will be recycled back into the plants’ roots.

Switchgrass diversity is also a benefit for those working in conservation, who need not be so limited in the varieties they can use. Weve been trying to help people working in restoration and conservation of prairielands to define what local means, Casler said. What weve found and other studies have found is that “local”, from a practical standpoint is pretty broad. If Im trying to restore a native prairie in central Iowa, then germplasm from eastern Nebraska to eastern Indiana is going to work without any problem at all.

The genetic diversity of plants from different sources across a wide geographic area will also help growers with switchgrass production on marginal lands, and to better respond to climate change.


Peer Reviewer

CenUSA Bioenergy is a coordinated research and education effort investigating the creation of a regional system in the Central US for producing advanced transportation fuels from perennial grasses on land that is either unsuitable or marginal for row crop production. In addition to producing advanced biofuels, the proposed system will improve the sustainability of existing cropping systems by reducing agricultural runoff of nutrients in soil and increasing carbon sequestration.

CenUSA is supported by Agriculture and Food Research InitiativeCompetitive Grant no. 2011-68005-30411 from theUSDA National Institute of Food and Agriculture.

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Living with Hereditary Breast and Ovarian Cancer Syndrome and Lynch Syndrome: Georgia

CDC Social Media posted a photo:

Living with Hereditary Breast and Ovarian Cancer Syndrome and Lynch Syndrome: Georgia

Please note that the personal stories in this album describe each individual’s experience with Lynch syndrome or Hereditary Breast and Ovarian Cancer Syndrome and are not meant to offer medical advice. Decisions about medical care should be made taking into consideration the facts, the science, and the patient’s values. The right decision for one patient may not be right for someone else.

Georgia’s Story
I want you to know that I am grateful every single day of my life that I do not have cancer. However, I am writing this to let you know that for some women, having their ovaries removed is not a cakewalk. I was extremely unprepared and felt very alone – I am writing this so you feel neither.

My strong family history of early onset colorectal cancer prompted me to seek out genetic counseling and genetic testing, although I was healthy and cancer-free. At the age of 40, I tested positive for Lynch syndrome, a hereditary cancer syndrome that makes it more likely that I will get colorectal and other cancers, including uterine (endometrial) and ovarian cancer. The words “ovarian cancer” are two of the scariest words for any woman to hear. Screening for ovarian cancer at this time is poor and usually by the time it is discovered, it is too late. Current recommendations for women with Lynch syndrome do not agree on one course of action, and the evidence is limited on which option results in better outcomes. Other women might choose to have more intense and more frequent screenings. I opted for surgery to remove my ovaries and uterus. I was 9 years old when my mother died, and the thought of leaving my 12-year-old son motherless horrified me.
Ovaries are not just for reproduction. The estrogen they create protects the heart and bones, prevents many forms of cancer from developing, and is necessary for high cognitive functioning. Estrogen also impacts skin elasticity, libido, and mood. The removal of my ovaries would have enormous psychological and physical implications for me and would impact how I view myself. The moment I awoke from my surgery, I found myself in the abyss of forced menopausal hell. With the passage of time and decreasing estrogen levels, my situation worsened. Two months following my surgery, I found myself on a downward spiral into a very dark and frightening place. I found myself becoming more introverted, quiet, and disconnected from things, people, and many of my passions. What I struggled with the most was the decline of my maternal instinct: I had to make a concerted effort to continue my role as a mother.

Fortunately, the passage of time, combined with a dedicated doctor, helped improve many of the negative side effects of my hysterectomy and oophorectomy. I was fortunate to find a doctor who understood the importance of using hormone replacement therapy that is specific for each individual. The psychological and psychiatric interventions I received were also helpful. While I do feel better, I will never be the same woman. While researching Lynch syndrome and other hereditary cancer syndromes, I noticed tremendous symmetry between them. Although the mutations may be different, the psychological and some physical aspects of hereditary cancers share more parallels than disparities. After speaking with many other women who have undergone prophylactic oophorectomy, I have discovered that I am not alone. We may have prevented the potential development of ovarian cancer, but at a huge cost. Removing body parts holds implications for the emotional and psychological aspects of one’s being. Still, after reading a great deal about ovarian cancer, I am confident I made the right decision.

Learn more about Lynch syndrome:

Disclaimer: Linking to a non-federal site does not constitute an endorsement by CDC, HHS, or any of its employees of the sponsors or the information and products presented on the site.

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Living with Hereditary Breast and Ovarian Cancer Syndrome and Lynch Syndrome: Georgia

Recommendation and review posted by Bethany Smith

Life Extension Nutrition Center Orlando

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease

The information provided on this site is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional or any information contained on or in any product label or packaging. You should not use the information on this site for diagnosis or treatment of any health problem or for prescription of any medication or other treatment. You should consult with a healthcare professional before starting any diet, exercise or supplementation program, before taking any medication, or if you have or suspect you might have a health problem. You should not stop taking any medication without first consulting your physician.

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Life Extension Nutrition Center Orlando

Recommendation and review posted by Bethany Smith

Genetic Testing Toledo OH – DNA Diagnostics Center

Jeffrey Paul Nunnari

3349 Executive Pkwy, Ste D Toledo, OH

Patricia Hayden Kurt


Tybo Alan Wilhelms

405 Madison Avenue, Suite 1300 Toledo, OH

Mark Davis


Melan M Forcht


David Charles Shook

3450 W Central Ave Ste 326 Toledo, OH

Martin Joseph Holmes

300 Madison Ave., 1200 Edison Plaza Toledo, OH

Amy Elizabeth Stoner

520 Madison Ave Ste 545 Toledo, OH

Tonya Marie Robinson

Four Seagate Suite 400 Toledo, OH

Stephen Terrance Priestap


People in Ohio shared their opinions about Paternity Testing

Do you personally know of anyone who has undergone paternity/maternity testing?

Yes: 68%

No: 26%

Unsure: 4%

Have you undergone paternity or maternity testing?

Yes: 13%

No: 84%

Rather not say: 1%

What was the reason that you underwent paternity/maternity testing?

Ordered by the court to prove I was/was not the parent: 16%

For my own proof that I was/was not the parent: 33%

To prove to the mother/father/child that I was/was not the parent: 16%

Other: 16%

Rather not say: 16%

Have any of your immediate family members ever undergone paternity/maternity testing?

Yes: 32%

No: 58%

Unsure: 9%

Please rate your level of agreement/disagreement with the following statement: It is a violation of constitutional rights and/or human rights for a court to order a person to undergo a paternity/maternity test.

Completely disagree: 48%

Mostly disagree: 18%

Neither agree or disagree: 20%

Mostly agree: 8%

Completely agree: 3%

Regarding the results of paternity/maternity tests, how well do you trust the results?

Completely distrust: 4%

Distrust: 2%

Unsure whether they are trustworthy or not: 19%

Trust: 50%

Completely trust: 23%


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Genetic Testing Toledo OH – DNA Diagnostics Center

Recommendation and review posted by Bethany Smith

Endocrine disease – Wikipedia, the free encyclopedia

Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.

Broadly speaking, endocrine disorders may be subdivided into three groups:[1]

Endocrine disorders are often quite complex, involving a mixed picture of hyposecretion and hypersecretion because of the feedback mechanisms involved in the endocrine system. For example, most forms of hyperthyroidism are associated with an excess of thyroid hormone and a low level of thyroid stimulating hormone.[2]

In endocrinology, medical emergencies include diabetic ketoacidosis, hyperosmolar hyperglycemic state, hypoglycemic coma, acute adrenocortical insufficiency, phaeochromocytoma crisis, hypercalcemic crisis, thyroid storm, myxoedema coma and pituitary apoplexy.[3]

Emergencies arising from decompensated pheochromocytomas or parathyroid adenomas are sometimes referred for emergency resection when aggressive medical therapies fail to control the patient’s state, however the surgical risks are significant, especially blood pressure lability and the possibility of cardiovascular collapse after resection (due to a brutal drop in respectively catecholamines and calcium, which must be compensated with gradual normalization).[4][5] It remains debated when emergency surgery is appropriate as opposed to urgent or elective surgery after continued attempts to stabilize the patient, notably in view of newer and more efficient medications and protocols.[6][7][8]

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Endocrine disease – Wikipedia, the free encyclopedia

Recommendation and review posted by Bethany Smith

Medical Weight Loss Clinic of Utah – Hormone Replacement …

Individualized Weight Loss Programs Read More

We take a physical / health approach to weight loss. There are hundred of people that diet and exercise daily and they still gain weight or they cant loose weight, this is not because they are cheating on their diet. Its because something is wrong with their body and their metabolism. Conditions that cause weight gain, also cause other symptoms i.e fatigue, brain fog, depression, anxiety, hair loss, feeling cold, belly weight, diabetes, low hormones and more. We customize our physician supervised weight loss programs for each of our patients after analyzing their unique health situation.

whether you have difficulty losing weight or are suffering from diabetes-related issues, PCOS, infertility, seemingly incurable migraines, or a host of other conditions.

At Medical Weight Loss and Hormone Replacement Clinic we dig deep to find the underlying causes of your health issues, then our physicians, dedicated staff, and nutritionists work directly with you to help solve your health problems!

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Medical Weight Loss Clinic of Utah – Hormone Replacement …

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Gene Therapy Market, 2015 – 2025 – Research and Markets

2 of 5

1. Preface 1.1. Scope of the Report 1.2. Research Methodology 1.3. Chapter Outlines

2. Executive Summary

3. Introduction 3.1. Context and Background 3.2. Historical Evolution of Gene Therapy 3.3. Classification of Gene Therapy 3.3.1. Somatic vs. Germline 3.3.2. Ex-vivo vs. In-vivo 3.4. Route of Administration 3.5. How Does Gene Therapy Work? 3.6. Advantages and Disadvantages of Gene Therapy 3.7. Ethical and Social Concerns in Gene Therapy 3.7.1. Somatic Gene Therapy 3.7.2. Germ-line Gene Therapy 3.8. Future Constraints and Challenges 3.8.1 Manufacturing 3.8.2 Reimbursement 3.8.3 Commercial Viability

4. Viral and Non-Viral Vectors 4.1. Chapter Overview 4.2. Viral Methods of Gene Transfer 4.2.1. Retroviruses 4.2.2. Lentiviruses 4.2.3. Adenoviruses 4.2.4. Adeno Associated Virus 4.2.5. Herpes Simplex Virus 4.2.6. Alphavirus 4.2.7. Vaccinia Virus 4.2.8. Simian Virus 4.3. Non-Viral Vectors 4.3.1. Naked/Plasmid Vectors 4.3.2. Biolistic Method: Gene Gun 4.3.3. Electroporation 4.3.4. Receptor Mediated Gene Delivery Methods 4.3.5. Liposomes, Lipoplexes and Polyplexes 4.3.6. Gene Activated Matrix (GAM)

5. Pipeline of Gene Therapy 5.1. Chapter Overview 5.2. Gene Therapy: Pipeline Analysis 5.3 Oncology: The Most Popular Therapeutic Area 5.4. Distribution of Gene Therapies by Phase of Development 5.5. Distribution of Gene Therapies by Type of Vector 5.6. Distribution of Gene Therapies by Type of Genes Targeted 5.7. Distribution of Gene Therapies by Type of Sponsor

6. Marketed Gene Therapies and Applications 6.1. Chapter Overview 6.2. Gendicine (SiBionoGeneTech) 6.2.1. Company and Pipeline Overview 6.2.2. History of Approval 6.2.3. Mechanism of Action and Vectors Used 6.2.4. Target Indication 6.2.5. Development Status 6.2.6. Dosage, Sales and Manufacturing 6.2.7. Patent Portfolio 6.2.8. Gendicine Sales Forecast, 2015 – 2025 6.3. Oncorine (Shanghai Sunway Biotech) 6.3.1. Company and Pipeline Overview 6.3.2. History of Approval 6.3.3. Mechanism of Action and Vectors Used 6.3.4. Target Indication 6.3.5. Development Status 6.3.6. Dosage and Sales 6.3.7. Patent Portfolio 6.3.8. Oncorine Sales Forecast, 2015 – 2025 6.4. Rexin-G (Epeius Biotechnologies) 6.4.1. Company and Pipeline Overview 6.4.2. History of Approval 6.4.3. Mechanism of Action and Vector Used 6.4.4. Target Indication 6.4.5. Development Status 6.4.6. Dosage and Manufacturing 6.4.7. Patent Portfolio 6.4.8. Rexin-G Sales Forecast, 2015 – 2025 6.5. Neovasculgen (Human Stem Cell Institute) 6.5.1. Company and Pipeline Overview 6.5.2. History of Approval 6.5.3. Mechanism of Action and Vector Used 6.5.4. Target Indication 6.5.5. Development Status 6.5.6. Dosage, Sales and Manufacturing 6.5.7. Neovasculgen Sales Forecast, 2015 – 2025 6.6. Glybera (uniQure) 6.6.1. Company and Pipeline Overview 6.6.2. History of Approval 6.6.3. Target Indication 6.6.4. Technology 6.6.5. Development Status 6.6.6. Dosage and Manufacturing 6.6.7. Collaborations 6.6.8. Glybera Sales Forecast, 2015 – 2025

7. Gene Therapy: Pipeline Products 7.1. Chapter Overview 7.2. Generx (Taxus Cardium) 7.2.1. Company and Pipeline Overview 7.2.2. History of Development 7.2.3. Target Indication 7.2.4. Technology 7.2.5. Development Status 7.2.6. Dosage and Manufacturing 7.2.7. Collaborations 7.2.8. Generx Sales Forecast, 2015 – 2025 7.3. TK (MolMedS.p.A) 7.3.1. Company and Pipeline Overview 7.3.2. History of Development 7.3.3. Target Indication 7.3.4. Technology 7.3.5. Development Status 7.3.6. Dosage and Manufacturing 7.3.7. Collaborations 7.3.8. TK Sales Forecast, 2015 – 2025 7.4. Collategene (AnGes MG) 7.4.1. Company and Pipeline Overview 7.4.2. History of Development 7.4.3. Target Indication 7.4.4. Technology 7.4.5. Development Status 7.4.6. Dosage and Manufacturing 7.4.7. Collaborations 7.4.8. Collategene Sales Forecast, 2015 – 2025 7.5. TissueGene-C (TissueGene Inc./Kolon Life Sciences) 7.5.1. Company and Pipeline Overview 7.5.2. History of Development 7.5.3. Target Indication 7.5.4. Technology 7.5.5. Development Status 7.5.6. Dosage and Manufacturing 7.5.7. Collaborations 7.5.8. TissueGene-C Sales Forecast, 2015 – 2025 7.6. SPK-RPE65 (Spark Therapeutics) 7.6.1. Company and Pipeline Overview 7.6.2. History of Development 7.6.3. Target Indication 7.6.4. Technology 7.6.5. Development Status 7.6.6. Dosage and Manufacturing 7.6.7. Collaborations 7.6.8. SPK-RPE65 Sales Forecast, 2015 – 2025 7.7. Prostvac (Bavarian Nordic) 7.7.1. Company and Pipeline Overview 7.7.2. History of Development 7.7.3. Target Indication 7.7.4. Technology 7.7.5. Development Status 7.7.6. Dosage and Manufacturing 7.7.7. Collaborations 7.7.8. Prostvac Sales Forecast, 2015 – 2025 7.8. T-VEC (Amgen) 7.8.1. Company and Pipeline Overview 7.8.2. History of Development 7.8.3. Target Indication 7.8.4. Technology 7.8.5. Development Status 7.8.6. Dosage and Manufacturing 7.8.7. Collaborations 7.8.8. T-Vec Sales Forecast, 2015 – 2025 7.9. ProstAtak (Advantagene) 7.9.1. Company and Pipeline Overview 7.9.2. History of Development 7.9.3. Target Indication 7.9.4. Technology 7.9.5. Development Status 7.9.6. Dosage and Manufacturing 7.9.7. Collaborations 7.9.8. ProstAtak Sales Forecast, 2015 – 2025 7.10. TroVax (Oxford BioMedica) 7.10.1. Company and Pipeline Overview 7.10.2. History of Development 7.10.3. Target Indication 7.10.4. Technology 7.10.5. Development Status 7.10.6. Dosage and Manufacturing 7.10.7. Collaborations 7.10.8. TroVax Sales Forecast, 2015 – 2025 7.11. Algenpantucel-L (Newlink Genetics Corporation) 7.11.1. Company and Pipeline Overview 7.11.2. History of Development 7.11.3. Target Indication 7.11.4. Technology 7.11.5. Development Status 7.11.6. Dosage and Manufacturing 7.11.7. Collaborations 7.11.8. Algenpantucel-L Sales Forecast, 2015 – 2025 7.12. ASP0113 (Vical/Astellas Pharma) 7.12.1. Company and Pipeline Overview 7.12.2. History of Development 7.12.3. Target Indication 7.12.4. Technology 7.12.5. Development Status 7.12.6. Dosage and Manufacturing 7.12.7. Collaborations 7.12.8. ASP0113 Sales Forecast, 2015 – 2025 7.13. E10A (Marsala Biotech) 7.13.1. Company and Pipeline Overview 7.13.2. History of Development 7.13.3. Target Indication 7.13.4. Technology 7.13.5. Development Status 7.13.6. Dosage and Manufacturing 7.13.7. Collaborations 7.13.8. E10A Sales Forecast, 2015 – 2025 7.14. Other Late Phase Gene Therapies 7.15. Overall Gene Therapy Market, 2015 – 2025

8. Promising Therapeutics Areas 8.1. Chapter Overview 8.2. Cancer 8.3. Neurological Disorders 8.3.1. Neurodegenerative Disorders 8.3.2. Lysosomal Storage Disorders (LSDs) 8.4. Ocular Diseases 8.5. Muscle Disorders 8.6. Blood Disorders (Anemia and Hemophilia) 8.7. Immunodeficiency Diseases

9. Gene Therapy: Additional Considerations 9.1. Chapter Overview 9.2 Venture Capital Investment in Gene Therapy 9.3. Conferences and Exhibitions on Gene Therapy 9.4. Contract Manufacturing in Gene Therapy

10. Conclusion 10.1. Move From Monogenic Diseases To Cancer 10.2. Controlled Gene Therapy for Optimised Gene Expression: Gradually Evolving 10.3. mRNA Mediated Gene Therapy: A Promising Approach to Improve Transfection Efficiency 10.4. Germline Gene Therapy: Potential yet to Unveil 10.5. A Strong Pipeline Likely To Result In A Multi-Billion Dollar Market

11. Interview Transcripts

12. Appendix 1: Tabulated Data

13. Appendix 2: List of Companies and Organisations

List of Tables: Table 3.1 Differences between Ex vivo and In vivo Gene Therapy Table 3.2 Price comparison of Marketed Gene Therapies Table 3.3 Approved ATMPs in EU Table 4.1 Features of Retrovirus Table 4.2 Features of Lentivirus Table 4.3 Features of Adenovirus Table 4.4 Features of Adeno-associated Virus Vectors Table 4.5 Features of Herpes Simplex Virus Vectors Table 5.1 Pipeline: Approved/Marketed Gene Therapies Table 5.2 Pipeline: Pre-registration/Phase III Gene Therapies Table 5.3 Pipeline: Phase II/III Gene Therapies Table 5.4 Pipeline: Phase II Gene Therapies Table 5.5 Pipeline: Phase I/II Gene Therapies Table 5.6 Pipeline: Phase I Gene Therapies Table 5.7 Pipeline: Preclinical Stage Table 5.8 Gene Therapy: University Spin-offs Table 6.1 Marketed and Approved Gene Therapies Table 6.2 Company Overview: SiBionoGeneTech Table 6.3 Gendicine: Status of Development Table 6.4 Gendicine: Patent Portfolio Table 6.5 Company Overview: Shanghai Sunway Biotech Table 6.6 H100 Series: Status of Development Table 6.7 Company Overview: Epeius Biotechnologies Table 6.8 Rexin-G: Status of Development Table 6.9 Rexin G: Patent Portfolio Table 6.10 Company Overview: Human Stem Cell Institute Table 6.11 Neovasculgen: Status of Development Table 6.12 Company Overview: uniQure Table 6.13 Glybera: Status of Development Table 7.1 Gene Therapy: Late Stage Development Products Table 7.2 Company Overview: Taxus Cardium Table 7.3 Generx: Status of Development Table 7.4 Company Overview: MolMedS.p.A. Table 7.5 TK: Status of Development Table 7.6 Company Overview: AnGes MG Table 7.7 Collategene: Status of Development Table 7.8 Company Overview: Kolon Life Science Table 7.9 TissueGene-C: Status of Development Table 7.10 Company Overview: Spark Therapeutics Table 7.11 SPK-RPE65: Status of Development Table 7.12 Company Overview: Bavarian Nordic Table 7.13 Prostvac: Status of Development Table 7.14 Company Overview: Amgen Table 7.15 T-Vec: Status of Development Table 7.16 Company Overview: Advantagene Table 7.17 ProstAtak: Status of Development Table 7.18 Company Overview: Oxford BioMedica Table 7.19 TroVax: Status of Development Table 7.20 Company Overview: NewLink Genetics Table 7.21 Algenpantucel-L: Status of Development Table 7.22 Company Overview: Vical Table 7.23 ASP0113: Status of Development Table 7.24 Company Overview: Marsala Biotech Table 7.25 E10A: Status of Development Table 7.26 Gene Therapies in Phase II/III Table 7.27 Important Highlights of Gene Therapies in Phase II/III Table 7.28 Gene Therapy: Expected Years of Launch Table 8.1 Gene Therapy for Cancer Table 8.2 Gene Therapy for Neurological Disorders Table 8.3 Classification of Lysosomal Storage Disorders Table 8.4 Gene Therapy for Lysosomal Storage Disorders Table 8.5 Gene Therapy for Ocular Disorders Table 8.6 Gene Therapy for Muscle Disorders Table 8.7 Gene Therapy for Blood Disorders Table 8.8 Gene Therapy for Immunodeficiency Diseases Table 9.1 Recent Investments in Gene Therapy Table 9.2 Gene Transfer: Conferences 2015 Table 9.3 Contract Manufactures in Gene Therapy Table 12.1 Pipeline Analysis: Distribution by Therapeutic Area Table 12.2 Pipeline Analysis: Distribution by Phase of Development Table 12.3 Pipeline Analysis: Distribution by Type Gene Delivery Methods Table 12.4 Pipeline Analysis: Distribution by the Gene Type Table 12.5 Pipeline Analysis: Distribution by Drug Developer Type Table 12.6 Gendicine: Sales Forecast 2015 – 2025, Base Scenario (USD Million Table 12.7 Gendicine: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.8 Gendicine: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.9 Oncorine: Sales Forecast 2015 – 2025, Base Scenario (USD Million Table 12.10 Oncorine: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.11 Oncorine: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.12 Rexin-G: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.13 Rexin-G: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.14 Rexin-G: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.15 Human Stem Cell Institute: Revenues (RUB 000) Table 12.16 Neovasculgen: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.17 Neovasculgen: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.18 Neovasculgen: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.19 Glybera: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.20 Glybera: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.21 Glybera: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.22 Generx: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.23 Generx: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.24 Generx: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.25 TK: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.26 TK: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.27 TK: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.28 Collategene: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.29 Collategene: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.30 Collategene: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.31 TissueGene-C: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.32 TissueGene-C: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.33 TissueGene-C: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.34 SPK-RPE65: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.35 SPK-RPE65: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.36 SPK-RPE65: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.37 Incidence and Mortality Rate 2012: Prostate Cancer Table 12.38 Prostvac: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.39 Prostvac: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.40 Prostvac: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.41 Incidence and Mortality Rate 2014: Melanoma Table 12.42 Skin Cancer: Geographical Distribution of Death Rate (Cases per 100,000 People) Table 12.43 T-Vec: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.44 T-Vec: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.45 T-Vec: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.46 Incidence and Mortality Rate 2012: Prostate Cancer Table 12.47 ProstAtak: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.48 ProstAtak: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.49 ProstAtak: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.50 Incidence and Mortality Rate 2012: Colorectal Cancer Table 12.51 TroVax: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.52 TroVax: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.53 TroVax: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.54 Age-Standardised Rate 2012: Pancreatic Cancer Table 12.55 Incidence and Mortality Rate 2012: Pancreatic Cancer Table 12.56 Algenpantucel-L: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.57 Algenpantucel-L: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.58 Algenpantucel-L: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.59 ASP0113: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.60 ASP0113: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.61 ASP0113: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.62 E10A: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Table 12.63 E10A: Sales Forecast 2015 – 2025, Conservative Scenario (USD Million) Table 12.64 E10A: Sales Forecast 2015 – 2025, Optimistic Scenario (USD Million) Table 12.65 Overall Gene Therapy Forecast 2015-2025: Base Scenario (USD Million) Table 12.66 Overall Gene Therapy Forecast 2015-2025: Conservative Scenario (USD Million) Table 12.67 Overall Gene Therapy Forecast 2015-2025: Optimistic Scenario (USD Million) Table 12.68 Contribution of Oncology in Gene therapy market (USD Million) Table 12.69 Number of Gene Therapies in Pre-clinical/Clinical Development for Cancer: By Disease Area Table 12.70 Number of Gene Therapies in Pre-clinical/Clinical Development for Cancer: By Transfer Vectors Table 12.71 Number of Gene Therapies in Pre-clinical/Clinical Development for Neurological Disorders: By Disease Area Table 12.72 Number of Gene Therapies in Pre-clinical/Clinical Development for Neurological Disorders: By Transfer Vectors Table 12.73 Number of Gene Therapies in Pre-clinical/Clinical Development for Lysosomal Storage Disorders: By Disease Area Table 12.74 Number of Gene Therapies in Pre-clinical/Clinical Development for Lysosomal Storage Disorders: By Transfer Vectors Table 12.75 Number of Gene Therapies in Pre-clinical/Clinical Development for Ocular Disorders: By Disease Area Table 12.76 Number of Gene Therapies in Pre-clinical/Clinical Development for Ocular Disorders: By Transfer Vectors Table 12.77 Number of Gene Therapies in Pre-clinical/Clinical Development for Muscle Disorders: By Disease Area Table 12.78 Number of Gene Therapies in Pre-clinical/Clinical Development for Muscle Disorders: By Transfer Vectors Table 12.79 Number of Gene Therapies in Pre-clinical/Clinical Development for Blood Disorders: By Disease Area Table 12.80 Number of Gene Therapies in Pre-clinical/Clinical Development for Blood Disorders: By Transfer Vectors Table 12.81 Number of Gene Therapies in Pre-clinical/Clinical Development for Immunodeficiency Diseases: By Disease Area Table 12.83 Number of Gene Therapies in Pre-clinical/Clinical Development for Immunodeficiency Diseases: By Transfer Vectors Table 12.83 Gene Therapy: Type of Investments in 2013 and 2014 Table 12.84 Gene Therapy: Investments made for different Body Systems Table 12.85 Gene Therapy Conferences in 2015: Distribution by Month Table 12.86 Contract Manufacturing in Gene Therapy: By Capability Table 12.87 Contract Manufacturing in Gene Therapy: By Location Table 12.88 Gene Therapy Market (USD Million), 2017, 2021 and 2025

List of Figures: Figure 3.1 History of Evolution: Timeline Figure 3.2 Gene Transfer using Viral Vectors Figure4.1 Gene Transfer: Viral and Non-Viral Methods Figure 5.1 Pipeline Analysis: Distribution by Therapeutic Area Figure 5.2 Pipeline Analysis: Distribution by Phase of Development Figure 5.3 Pipeline Analysis: Distribution by Type of Vector Figure 5.4 Pipeline Analysis: Distribution by Target Gene Type Figure 5.5 Pipeline Analysis: Distribution by Drug Developer Type Figure 6.1 Pipeline Overview: SiBionoGeneTech Figure 6.2 Gendicine: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 6.3 Pipeline Overview: Shanghai Sunway Biotech Figure 6.4 Adenovirus Construct in Oncorine Figure 6.5 Oncorine: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 6.6 Pipeline Overview: Epeius Biotechnologies Figure 6.7 Rexin-G: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 6.8 Pipeline Overview: Human Stem Cell Institute Figure 6.9 Human Stem Cell Institute: Revenues (RUB000) Figure 6.10 Neovasculgen: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 6.11 Pipeline Overview: uniQure Figure 6.12 Glybera: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure7.1 Pipeline Overview: TaxusCardium Figure 7.2 Generx: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.3 Pipeline Overview: MolMedS.p.A. Figure 7.4 TK: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.5 Pipeline Overview: AnGes Figure 7.6 Collategene: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.7 Pipeline Overview: Kolon Life Science Figure 7.8 TissueGene-C: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.9 Pipeline Overview: Spark Therapeutics Figure 7.10 SPK-RPE65: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.11 Pipeline Overview: Bavarian Nordic Figure 7.12 Incidence and Mortality 2012: Prostate Cancer (in 000) Figure 7.13 Prostvac: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.14 Pipeline Overview: Amgen Figure 7.15 Incidence and Mortality 2014: Melanoma (in 000) Figure 7.16 Skin Cancer: Geographical Distribution of Death Rate (Cases per 100,000 People) Figure 7.17 T-Vec: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.18 Pipeline Overview: Advantagene Figure 7.19 Incidence and Mortality 2012: Prostate Cancer (in 000) Figure 7.20 ProstAtak: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.21 Pipeline Overview: Oxford BioMedica Figure 7.22 Incidence and Mortality 2012: Colorectal Cancer (in 000) Figure 7.23 TroVax: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.24 Pipeline Overview: NewLink Genetics Figure 7.25 Age-Standardised Rate 2012: Pancreatic Cancer Figure7.26 Incidence and Mortality 2012: Pancreatic Cancer (in 000) Figure 7.27 Algenpantucel-L: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.28 Pipeline Overview: Vical Figure 7.29 ASP0113: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.30 Pipeline Overview: Marsala Biotech Figure 7.31 E10A: Sales Forecast 2015 – 2025, Base Scenario (USD Million) Figure 7.32 Overall Gene Therapy Market Outlook 2015-2025 (USD Million) Figure 7.33 Contribution of Oncology to Gene Therapy Market Figure 8.1 Number of Gene Therapies in Pre-clinical/Clinical Development for Cancer: By Disease Area Figure 8.2 Number of Gene Therapies in Pre-clinical/Clinical Development for Cancer: By Transfer Vectors Figure 8.3 Number of Gene Therapies in Pre-clinical/Clinical Development for Neurological Disorders: By Disease Area Figure 8.4 Number of Gene Therapies in Pre-clinical/Clinical Development for Neurological Disorders: By Transfer Vectors Figure 8.5 Number of Gene Therapies in Pre-clinical/Clinical Development for Lysosomal Storage Disorders: By Disease Area Figure 8.6 Number of Gene Therapies in Pre-clinical/Clinical Development for Lysosomal Storage Disorders: By Transfer Vectors Figure 8.7 Number of Gene Therapies in Pre-clinical/Clinical Development for Ocular Disorders: By Disease Area Figure 8.8 Number of Gene Therapies in Pre-clinical/Clinical Development for Ocular Disorders: By Transfer Vectors Figure 8.9 Number of Gene Therapies in Pre-clinical/Clinical Development for Muscle Disorders: By Disease Area Figure 8.10 Number of Gene Therapies in Pre-clinical/Clinical Development for Muscle Disorders: By Transfer Vectors Figure 8.11 Number of Gene Therapies in Pre-clinical/Clinical Development for Blood Disorders: By Disease Area Figure 8.12 Number of Gene Therapies in Pre-clinical/Clinical Development for Blood Disorders: By Transfer Vectors Figure 8.13 Number of Gene Therapies in Pre-clinical/Clinical Development for Immunodeficiency Diseases: By Disease Area Figure 8.14 Number of Gene Therapies in Pre-clinical/Clinical Development for Immunodeficiency Diseases: By Transfer Vectors Figure 9.1 Gene Therapy: Type of Investments in 2013 and 2014 Figure 9.2 Gene Therapy: Investments Made for Different Body Systems (USD Million) Figure 9.3 Gene Therapy Conferences in 2015: Distribution by Month Figure 9.4 Gene Transfer: Top Conference Sponsors Figure 9.5 Contract Manufacturing in Gene Therapy: By Capability Figure 9.6 Contract Manufacturing in Gene Therapy: By Location Figure 10.1 Gene Therapy Market (USD Million), 2017, 2021 and 2025

Note: Product cover images may vary from those shown

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Gene Therapy Market, 2015 – 2025 – Research and Markets

Recommendation and review posted by Bethany Smith

Life Extension – Google+


The latest research on health, wellness, nutrition, & aging. Offering unique, premium quality dietary supplements, vitamins, minerals, herbs, & hormones.


The latest research on health, wellness, nutrition, & aging. Offering unique, premium quality dietary supplements, vitamins, minerals, herbs, & hormones.

Life Extension – Google+

Recommendation and review posted by Bethany Smith

Standards in Cell Therapy

This is a sixth post of the series Not Lost in Translation.

If youre trying to develop a cellular product and just entering the field of cell therapy, you should be aware of existent standards. Why is it important? Knowing standards in your field allows to:

Even though, cell therapy filed relatively new, there are numerous related standards. Unfortunately, many professionals are unaware about organizations and standards in cell therapy field. The purpose of this post is to indicate few leadig organizations, providing standards and types of standards in cell products development. Significant part of this topic was summarized from the recent public FDA workshop Synergizing Efforts in Standards Development for Cellular Therapies and Regenerative Medicine Products.

Type of standards in cell therapy:

Standards-developing organizations and examples: ISO International Organization for Standardization Developing and providing international standards, including medical devices, laboratory testing and some, related to cell therapy and tissue engineered products. Examples: ISO/TC 194/SC 1 Tissue product safety ISO/TC 150/SC 7 Tissue-engineered medical products

ASTM International American Society for Testing and Materials ASTM leading international standards organization. ASTM has Subcommittee F04.43 for developing standards in cell therapy and tissue engineering. Examples: ASTM F2210 Standard Guide for Processing Cells, Tissues, and Organs for Use in Tissue Engineered Medical Products ASTM F2739 Standard Guide for Quantitating Cell Viability Within Biomaterial Scaffolds ASTM F2315 Standard Guide for Immobilization or Encapsulation of Living Cells or Tissue in Alginate Gels ASTM F2944 Standard Test Method for Automated Colony Forming Unit (CFU) Assays

USP U.S. Pharmacopeial Convention Provides standards for use ancillary and raw materials for cellular and tissue products. Examples: Chapter 1046 Cell and Gene Therapies Products Chapter 1047 Gene Therapy Products Chapter 1043 Ancillary Materials for Cell, Gene and Tissue-Engineered Products Chapter 92 Growth Factors and Cytokines Used in Cell Therapy Manufacturing Chapter 90 Fetal Bovine SerumQuality Attributes and Functionality Tests

GBSI Global Biological Standard Institute Developing standards for life sciences, including biomedical research.

ATCC American Type Culture Collection Manufactures and provides reference material (including cells), developing biological standards for basic and translational research. Examples: ATCC Certified reference material ATCC Standards Development Organization

BSI British Standards Institution Has a project for developing regenerative medicine definitions and guidelines for clinical cell products characterization. Examples: PAS 93:2011 Characterization of human cells for clinical applications. Guide PAS 84:2012 Cell therapy and regenerative medicine. Glossary

FACT Foundation for the Accreditation of Cellular Therapy Provides standards for collection and processing cellular products. Accredits clinical stem cell labs, cord blood banks and more than minimal manipulation cell therapy facilities. Examples: FACT-JACIE International Standards for Cellular Therapy Product Collection, Processing and Administration FACT-JACIE Cellular Therapy Accreditation Manual

AABB American Association of Blood Banks Center for Cellular Therapies In cell therapy field, AABB has very similar functions with FACT. Examples: Standards for Cellular Therapy Services

ICCBBA International Council for Commonality in Blood Bank Automation Management of the ISBT-128 Standard the terminology, identification, coding and labeling of medical products of human origin (including blood, cell, tissue, and organ products).

ISCT International Society for Cellular Therapy ISCT leverages expertise of cell therapy professionals to develop guidelines and recommendations for cellular products development, characterization, and quality. Examples: Minimal criteria for defining multipotent mesenchymal stromal cells Potency assay development for cellular therapy products Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells IFATS/ISCT statement

Coordination and harmonization As you can see, there are many organizations, involved in different aspects of cell therapy standardization. How can we make sure that there are no overlaps between them? How to coordinate and harmonize their activities? There are some good existent examples of such coordination:

*********************** This post is a part of Not Lost in Translation online community project. In this series we will try to bridge the translational gaps between scientific discovery in research labs and clinical cell applications for therapies. We will look at challenges in translation of cell product development and manufacturing in academic and industry settings. If you would like to contribute to this community project, please contact us!

Tagged as: cell therapy, reference material, standard, translation

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Standards in Cell Therapy

Recommendation and review posted by Bethany Smith

The Genetics of Calico Cats – Department of Biology

In mammals, sex is determined by two sex chromosomes, known as the X and the Y chromosomes. Genes located on either the X or the Y chromosome are known as “sex-linked” genes. Genes on any chromosomes other than the X or Y are known as autosomal genes. The Karyotype: A Visualization of the Chromosomes Normal female mammals have two X chromosomes. Normal males have one X and one Y chromosome. This can be seen in this human male karyotype: The X and Y chromosomes appear at the bottom right corner of the image. If this were a female, the two sex chromosomes would both be relatively larger X chromosomes. As you can see, compared to the X chromosome, the Y chromosome is small and carries fewer genes.

The exact genes carried on the X chromosome varies among species. In humans, for example, the gene coding for normal clotting factors and the gene coding for normal cone photoreceptor pigment are located on the X chromosome. Abnormal mutant forms of these genes can result in hemophilia (a potentially fatal disorder in which the blood fails to clot) in the former case, and red-green color blindness in the latter.

There are two possible (normal) male genotypes:

At a certain point in the embryonic development of every female mammal (including cats), one of the two X chromosomes in each cell inactivates by supercoiling into a structure known as a Barr Body. This irreversible process is known as Lyonization; it leaves only ONE active X chromosome in each cell of the female embryo. Only the alleles on the active (uncoiled) X chromosome are expressed.

Lyonization is random in each cell: there’s no way to predict which of the two X chromosomes will become inactivated. Hence, any given cell of a heterozygous female could end up as either of the following:

A heterozygous cat will be a patchwork of these two types of cells. Lyonization takes place relatively early in development, when the cat is still a blastula, and all the cells descended from a blastomere with a particular X chromosome inactivated as a Barr Body will also have the same Barr Body inactivated. That means that all the skin tissues that arise from a cell like the left one will express black fur, and all the skin tissue that arise from a cell like the right one will express orange fur. Hence:

Here’s an overview:

This is why calico cats are almost invariably female.

A calico cat is a tortoiseshell expressing an additional genetic condition known as piebalding. A piebald animal has patches of white (i.e., unpigmented) skin/fur. This is controlled by a different locus (S) than the black/orange fur colors.

The patches may be relatively large, or rather small and interwoven:

Larger patches may be caused by:

See more here:
The Genetics of Calico Cats – Department of Biology

Recommendation and review posted by Bethany Smith

Tortoiseshell cat – Wikipedia, the free encyclopedia

Tortoiseshell describes a coat coloring found almost exclusively in female cats,[1][2] so called because of the similarity to the tortoiseshell material. Also called Torties for short, these cats combine two colors other than white, either closely mixed or in large patches.[2] The colors are often described as red and black, but “red” can instead be orange, yellow, or cream[2] and “black” can instead be chocolate, grey, tabby, or blue.[2] A tortoiseshell cat with the tabby pattern as one of its colors is a Torbie.

“Tortoiseshell” is typically reserved for cats with relatively small or no white markings. Those that are largely white with tortoiseshell patches are described as tricolor,[2] tortoiseshell-and-white (in the United Kingdom), or calico (in Canada and the United States). Tortoiseshell markings appear in many different breeds as well as in non-purebred domestic cats.[3] This pattern is especially preferred in the Japanese Bobtail breed.[4]

Tortoiseshell cats have coats with patches of various shades of red and black, as well as white. The size of the patches can vary from a fine speckled pattern to large areas of color. Typically, the more white a cat has, the more solid the patches of color. Dilution genes may modify the coloring, lightening the fur to a mix of cream and blue, lilac or fawn. The markings on tortoiseshell cats are usually asymmetrical. Occasionally tabby patterns of black and brown (eumelanistic) and red (phaeomelanistic) colors are also seen. These patched tabbies are often called tortie-tabby, torbie or, with large white areas, caliby.[5] Tortoiseshell can also be expressed in the point pattern.

Frequently there will be a “split face” pattern with black on one side of the face and orange on the other, with the dividing line running down the bridge of the nose.

Tortoiseshell and calico coats result from an interaction between genetic and developmental factors. The primary gene for coat color (B) for the colors brown, chocolate, cinnamon, etc., can be masked by the co-dominant gene for the orange color (O) which is on the X Chromosome and has two alleles, the Orange (XO) and not-Orange (Xo), that produce orange phaeomelanin and black eumelanin pigments, respectively. (NOTE: Typically, the X for the chromosome is assumed from context and the alleles are referred to by just the uppercase O for the orange, or lower case o for the not-orange.) The Tortoiseshell and Calico cats are indicated: Oo to indicate they are heterozygous on the O gene. The (B) and (O) genes can be further modified by a recessive dilute gene (dd) which softens the colors. Orange becomes Cream, Black becomes Gray, etc. Various terms are used for specific colors, for example, Gray is also called Blue, Orange is also called Ginger. Therefore a Tortoiseshell cat may be a Chocolate Tortoiseshell or a Blue/Cream Tortoiseshell or the like, based on the alleles for the (B) and (D) genes.

The cells of female cats, which like other mammalian females have two X chromosomes (XX), undergo the phenomenon of X-inactivation,[6][7] in which one or the other of the X-chromosomes is turned off at random in each cell in very early development. The inactivated X becomes a Barr body. Cells in which the chromosome carrying the Orange (O) allele is inactivated express the alternative non-Orange (o) allele, determined by the (B) gene. Cells in which the non-Orange (o) allele is inactivated express the Orange (O) allele. Pigment genes are expressed in melanocytes that migrate to the skin surface later in development. In bi-colored tortoiseshell cats, the melanocytes arrive relatively early, and the two cell types become intermingled, producing the characteristic brindled appearance consisting of an intimate mixture of orange and black cells, with occasional small diffuse spots of orange and black.

In tri-colored calico cats, a separate gene interacts developmentally with the coat color gene. This spotting gene produces white, unpigmented patches by delaying the migration of the melanocytes to the skin surface. There are a number of alleles of this gene that produce greater or lesser delays. The amount of white is artificially divided into mitted, bicolor, harlequin, and van, going from almost no white to almost completely white. In the extreme case, no melanocytes make it to the skin and the cat is entirely white (but not an albino). In intermediate cases, melanocyte migration is slowed, so that the pigment cells arrive late in development and have less time to intermingle. Observation of tri-color cats will show that, with a little white color, the orange and black patches become more defined, and with still more white, the patches become completely distinct. Each patch represents a clone of cells derived from one original cell in the early embryo.[8]

A male cat, like males of other therian mammals, has only one X and one Y chromosome (XY). That X chromosome does not undergo X-inactivation, and coat color is determined by which allele is present on the X. Accordingly the cat’s coat will be either entirely orange or non-orange. Very rarely (approximately 1 in 3,000[9]) a male tortoiseshell or calico is born. These animals typically have an extra X chromosome (XXY), a condition known in humans as Klinefelter syndrome, and their cells undergo an X-inactivation process like that in females. As in humans, these cats often are sterile because of the imbalance in sex chromosomes. Some male calico or tortoiseshell cats may be chimeras, which result from the fusion in early development of two embryos with different color genotypes. Others are mosaics, in which the XXY condition arises after conception and the cat is a mixture of cells with different numbers of X chromosomes.

Cats of this coloration are believed to bring good luck in the folklore of many cultures.[10] In the United States, these are sometimes referred to as money cats.[11]

According to cat expert Jackson Galaxy, tortoiseshell cats tend to have a much more distinct personality.[12] The magazine of the Smithsonian Institution has reported that studies suggest many tortoiseshell owners believe their cats have increased attitude and they call it “tortitude” but science does not support this.[13]

Continued here:
Tortoiseshell cat – Wikipedia, the free encyclopedia

Recommendation and review posted by Bethany Smith

Cloning Myths – Learn Genetics

In What is cloning? we learned what it means to clone an individual organism. Given its high profile in the popular media, the topic of cloning brings up some common, and often confusing, misconceptions.

Let’s say you wanted a clone to do your homework. After reviewing What is Cloning? and Click and Clone, you’ve figured out, generally, how to make a clone. Knowing what you know, do you think this approach would really help you finish your homework…this decade?

A common belief is that a clone, if created, would magically appear at the same age as the original. This simply isn’t true. You remember that cloning is a way to create an embryo, not a full-grown individual. The embryo, once created, must develop exactly the same way as a regular embryo made by joining egg and sperm. Your clone would need a surrogate mother and ample time to grow and fully develop into an individual.

Your beloved cat Frankie has been a loyal companion for years. Recently, though, Frankie has been showing signs of old age, and you realize that your friend’s days are numbered. You can’t bear the thought of living without her, so you contact a biotechnology company that advertises pet cloning services. For a fee, this company will clone Frankie using DNA from a sample of her somatic cells. You’re thrilled: you’ll soon have a carbon copy of Frankiewe’ll call her Frankie #2and you’ll never have to live without your pal! Right?

Not exactly. Are you familiar with the phrase “nature versus nurture?” Basically, this means that while genes help determine traits, environmental influences have a considerable impact on shaping an individual’s physical appearance and personality. For example, do you know any identical twins? They are genetically the same, but do they really look and act exactly alike?

So, even though Frankie #2 is genetically identical to the original Frankie, she will grow and develop in a completely different environment than the original Frankie, she will have a different mother, and she will be exposed to different experiences throughout her development and life. Therefore, there is only a slim chance that Frankie #2 will closely resemble the Frankie you know and love.

Another difference between a clone and the original is the mitochondria. Mitochondria are organelles that sit inside nearly every cell. Their job is to burn fuel (from the food we eat) to make energy. Mitochondria have their own chromosome, made of DNA and divided into genes, and they divide as our cells divide.

We get our mitochondria from our mothers. Egg cells are packed with mitochondria, which are copied and distributed to new cells as they form. When a clone is made using nuclear transfer, the egg cell that’s used to receive the donor nucleus is already filled with mitochondria contributed by the egg donor. As the clone develops, its cells will be filled with these mitochondriaand their genesrather than the mitochondria from the DNA donor.

Nature vs. Nurture. Find out why twins become increasingly different as they age in Epigenetics.

Clones can be made in the lab through artificial embryo twinning or nuclear transfer. But these aren’t the only ways to make a clone.

Clones are simply identical genetic copies. Many organisms reproduce through cloning as a matter of course, through a process called asexual reproduction. Bacteria, yeast, and single-celled protozoa multiply by making copies of their DNA and dividing in two. Redwood and aspen trees send up shoots from their roots, which grow into trees that are genetically identical to the parent.

In the animal world, the eggs of female aphids grow into identical genetic copies of their motherwithout being fertilized by a male. If a starfish is chopped in half, both pieces can regenerate, forming two complete, genetically identical individuals. Even mammals form natural clones: identical twins are a common example in many species.

Learn more about Sexual and Asexual Reproduction.

Humans have been cloning plants for at least a couple thousand years. Many of the fruits we eatincluding bananas, grapes, and applescome from artificially created clones. Unlike the complex process of cloning a mammal, cloning a plant can be as simple as cutting a branch from one tree and grafting it onto another.

Animal cloning also has a long history. Artificial embryo twinning, which involves dividing an early embryo to form separate, genetically identical organisms, was first done in a vertebrate over 100 years ago. And the first successful nuclear transfer was done in a frog in the 1970s.

Learn more about The History of Cloning.

While animal cloning still has a high failure rate, and some well-known clones (including Dolly the sheep) have had health problems, clones are not necessarily “damaged.” Many live long, healthy lives. One racing mule clone was at one time ranked third in the world. And a barrel-racing horse clone was not only born healthy, but at two years old he was also collecting a stud fee of $4,000 for his owners.

One reason for cloning’s high failure rate seems to be incomplete resetting of the somatic cell’s DNA. During egg and sperm formation, DNA is “reset” to a baseline or embryonic state. As the embryo develops, cells begin to differentiate into muscle, nerve, liver, and other types. Part of the differentiation process involves adding and removing chemical tags on the DNA, which keeps genes turned “on” that are necessary for the function of that cell type and keeps others turned “off.”

Learn more about this process in Epigenetics.

APA format: Genetic Science Learning Center (2014, June 22) Cloning Myths. Learn.Genetics. Retrieved September 25, 2015, from MLA format: Genetic Science Learning Center. “Cloning Myths.” Learn.Genetics 25 September 2015 Chicago format: Genetic Science Learning Center, “Cloning Myths,” Learn.Genetics, 22 June 2014, (25 September 2015)

Read the original here:
Cloning Myths – Learn Genetics

Recommendation and review posted by Bethany Smith

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HRT | Hormone Replacement Therapy | Testosterone

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Contact a Physician – Hormone Therapy – BodyLogicMD

BodyLogicMD’s affiliated physicians are the most highly trained in natural bioidentical hormone replacement therapy with integrated fitness and nutrition programs which they have been providing to their patients since 2003. And their patients are pleased!

BodyLogicMD has been given anA+rating with the Better Business Bureau. That is the highest rating a business can get from the BBB, and it means that its customers are highly and consistently satisfied with the services they receive. You can rest assured that when you visit a BodyLogicMD affiliated physician, you’ll get the care you deserve.

Contact a Physician – Hormone Therapy – BodyLogicMD

Recommendation and review posted by Bethany Smith