April 17, 2017 09:48 ET | Source: Research and Markets

Dublin, April 17, 2017 (GLOBE NEWSWIRE) -- Research and Markets has announced the addition of Jain PharmaBiotech's new report "Gene Therapy - Technologies, Markets and Companies" to their offering.

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression.

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2015, over 2050 clinical trials have been completed, are ongoing or have been approved worldwide.A breakdown of these trials is shown according to the geographical areas and applications.

Gene therapy markets are estimated for the years 2016-2026. The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright.The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

Profiles of 187 companies involved in developing gene therapy are presented along with 232 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold within a decade. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report. John Wiley & Sons published the book in 2000 and from 2001 to 2003, updated versions of these companies (approximately 160 at mid-2003) were available on Wiley's web site. Since that free service was discontinued and the rights reverted to the author, this report remains the only authorized continuously updated version on gene therapy companies.

Key Topics Covered:

Part I: Technologies & Markets

0. Executive Summary

1. Introduction

2. Gene Therapy Technologies

3. Clinical Applications of Gene Therapy

4. Gene Therapy of Genetic Disorders

5. Gene Therapy of Cancer

6. Gene Therapy of Neurological Disorders

7. Gene Therapy of Cardiovascular Disorders

8. Gene therapy of viral infections

9. Research, Development and Future of Gene Therapy

10. Regulatory, Safety, Ethical Patent Issues of Gene Therapy

11. Markets for Gene Therapy

12. References

Part II: Companies

13. Companies involved in Gene Therapy

For more information about this report visit http://www.researchandmarkets.com/research/d5gdwq/gene_therapy

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Recommendation and review posted by Bethany Smith

John Webb, Special to The Clarion-Ledger 8:02 p.m. CT April 15, 2017

Type 2 diabetes can wreak havoc on your health. While lifestyle changes can help keep diabetes under control, many patients require oral medications or insulin injections as forms of treatment, too. Watch the video for how diabetes affects your body. Time

Mary Fortune, executive vice president of the Diabetes Foundation of Mississippi, pictured here with Bailey, one of DFM's Diabetic Alert Dogs, has lived with the disease 50 years.(Photo: Special to The Clarion-Ledger)

To invert a popular adage, it can take a child to raise a village or, in this case, a child who grew up with diabetes and as an adult vividly recalls what it was like.

A self-described free spirit, Mary Fortune has trekked the world despite a particularly brittle case of type 1 diabetes, traveling the Pacific Coast Highway on the back of a motorcycle, even in the immediate aftermath of a low blood sugar episode, and riding the rails of Europe, where she remembers asking for food from a train window in Hamburg during another hypoglycemic moment (blood glucose monitoring was not available in those days).

But she had one limitation.

She was told that because of her condition she should never try to get pregnant. That was the conventional wisdom in those days.

Yet, as she marks her 50th anniversary with diabetes a demanding and often unforgiving life partner Fortune says she feels as if she has raised an enormous family of those from across the state who like her had to come to terms in their youth or childhood with multiple daily insulin injections, finger sticks, blood sugar highs and lows, rigorous attention to diet and exercise and the kind of health complications that can beset even the most conscientious.

Theyre all my children, hundreds who have grown up with diabetes, and Im still in touch with quite a few, said Fortune, executive vice president of the Diabetes Foundation of Mississippi. Ive followed their lives and careers, engagements, weddings, births, successes and failures, times of crisis and grief, and times of joy.

And making this Mississippi matriarch of diabetes particularly proud this week are those children and adults she has mentored over the years who will be participating in the Diabetes Foundations 14th Annual Ultimate Fashion Show and Champagne Luncheon from 11 a.m to 1 p.m. Thursday at the Country Club of Jackson.

Proceeds will go to support the foundations Camp Kandu for children with diabetes and their families. The need has never been greater, because new studies have shown the rates of children being diagnosed with both Type 1 and Type 2 diabetes have increased dramatically, especially among racial and ethnic minorities.

Nationally between 2001 and 2009,the prevalence of Type 1 diabetes increased 21 percent among children up to age 19, according to astudy funded by the Centers for Disease Control and Prevention and the National Institutes of Health. The prevalence of Type 2 diabetes among those ages 10 to 19 rose 30 percent during the same period, the study, released in 2014, found.Type 1 diabetes is a chronic condition in which the pancreas produces little or no insulin, the hormone needed to allow sugar into cells to produce energy. Type 2 diabetesoccurs when the body becomes resistant to insulin or doesn't make enough insulin.

We are up at Batson Childrens Hospital seeing newly diagnosed children far more than we used to be, Fortune said.

RELATED:Diabetes and children: A balancing act

SEE ALSO:UMMC Delta diabetes project improves use of telehealth

Among those taking to the runway will be Charlie Mozingo, 41, the founder of Mozingo Clothiers in Fondren, who was introduced to Fortune after his diagnosis at the age of 10 and who in adulthood has been working with the foundation as a volunteer and board member.

Mozingo Clothiers is excited to be a part of this years fashion show, he said. We are dressing seven gentlemen in everything from custom clothing to some of our more casual attire. (As GQ might advise, Look for bold windowpanes in sport coats with lightweight materials that are both soft and comfortable, Mozingo said.)

Also taking part will be the foundations communications coordinator, Kaitlan Alford, 23, who was diagnosed with Type 1 at age 9 after spending two days in a coma.

My diagnosis was dramatic for everyone, really intense, and I saw how it affected my family, she said. We were all in a sense diagnosed. My mother saw me going through all this, the 2 a.m. blood sugar checks every night, but she knew I could handle it and take care of myself, which made me feel like I could do anything.

Kaitlan Alford, diagnosed as a child with Type 1 diabetes, was 14 when she walked the runway nine years ago at the Ultimate Fashion Show and Champagne Brunch in Jackson to raise money for the Diabetes Foundation of Mississippi's children's programs. Now an adult, she is the foundation's communications coordinator.(Photo: Special to The Clarion-Ledger)

Soft-spoken and demure, Alford had to fight back tears as she recalled how the disease has affected her mother, as well as the way Fortune reached out to her, first as a friend and mentor but then as the one who hired her after college.

I get emotional when I talk about it, Alford said. I dont just work here. Its not just us helping others. Mary helps me. We talk about things we both go through, trying to juggle the complex set of challenges that diabetes presents while at the same time trying to live a normal life.

Kaitlan Alford, 23, communications coordinator for the Diabetes Foundation of Mississippi, first walked the runway at the foundation's Ultimate Fashion Show and Champagne Brunch in Jackson. Alford, who has Type 1 diabetes, still participates in the event that raises money for the foundation's children's programs.(Photo: Special to The Clarion-Ledger)

At one of the foundations many statewide fund-raising walks, a child touched Alfords life in a way that she said still stands out in her mind.

My mom walked over to me and introduced me to this tiny, blond curlyhaired boy with blue eyes that could melt anyones heart, Alford said. He was 3 years old, and he had been diagnosed with Type 1 at 18 months."

She said that her eyes immediately filled with tears. Describing how I felt is nearly impossible, Alford said. I was hurting for him because I knew what he was going through, and I was empowered by him because he was 3 and dealing with challenges I didnt have to face until I was 9.

Ayden Wolken, 10, seen here with a bull at this year's Dixie National Rodeo Show, was diagnosed with diabetes when he was 18 months old.(Photo: Special to The Clarion-Ledger)

Alford said the boy, Ayden Wolken of Mendenhall, now 10 and competing on the soccer field and at livestock shows, inspired her to be even more courageous and determined while living with diabetes. Seeing him thriving now continues to inspire me, she said.

These are the kinds of moments that those at the Diabetes Foundation of Mississippi make possible because of their passion for not merely helping others, but for changing lives.

The Diabetes Foundation of Mississippis 14th Annual Ultimate Fashion Show and Champagne Luncheon will feature models of all ages in spring and summer fashions, giveaways and an array of raffle items, as well as a Champagne lunch and a drawing for the 2017 Patty Peck Honda Car 4 a Cure. All money raised by the foundation remains in Mississippi to be used to improve the quality of life of children and adults with diabetes.

Being honored will be the foundations 2017 Women of Excellence, Dr. Jane-Claire Boyd Williams of GI Associates and Dr. Beverly Hogan, president of Tougaloo College.

What: The Diabetes Foundation of Mississippis 14th Annual Ultimate Fashion Show and Champagne Luncheon

Where: The Country Club of Jackson

When:11 a.m.-1 p.m. April 20

Cost: $70 per ticket

For more information, call 601-957-7878 or visit msdiabetes.org (click on Events).

Type 1 diabetes, formerly known as juvenile or insulin-dependent diabetes, isa chronic condition in which the pancreas produces little or no insulin, the hormone needed to allow sugar into cells to produce energy.

Type 2 diabetes, once call adult-onset diabetes, occurs when the body becomes resistant to insulin or doesn't make enough insulin.

Source: Mayo Clinic

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Diabetes drives children to help others - Jackson Clarion Ledger

Recommendation and review posted by Bethany Smith

Scientists have created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. The discovery is a major step forward in treating patients with tissue damage after a heart attack, researchers at University of Minnesota in the US said. During a heart attack, a person loses blood flow to the heart muscle and that causes cells to die.

Our bodies can not replace those heart muscle cells so the body forms scar tissue in that area of the heart, which puts the person at risk for compromised heart function and future heart failure. Researchers used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

When the cell patch was placed on a mouse following a simulated heart attack, the researchers saw significant increase in functional capacity after just four weeks. Since the patch was made from cells and structural proteins native to the heart, it became part of the heart and absorbed into the body, requiring no further surgeries. This is a significant step forward in treating the No 1 cause of death in the US, said Brenda Ogle, an associate professor at the University of Minnesota.

We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years, said Ogle. Ogle said that the research is different from previous ones as the patch is modelled after a digital, three- dimensional scan of the structural proteins of native heart tissue. The digital model is made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells.

Only with 3D printing of this type can we achieve one micron resolution needed to mimic structures of native heart tissue, researchers said. We were quite surprised by how well it worked given the complexity of the heart. We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch, Ogle said.

Ogle said they are already beginning the next step to develop a larger patch that they would test on a pig heart, which is similar in size to a human heart. The study was published in the journal Circulation Research.

Publish date: April 16, 2017 12:57 pm| Modified date: April 16, 2017 12:57 pm

Tags: 3D-Bioprint, Brenda Ogle, cells, Heart, heart attack, heart failure, Journal Circulation Research, scientists, structural proteins, University of Minnesota

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Scientists have made a 3D-printed patch that can help heal the damaged heart tissue - Tech2 (blog)

Recommendation and review posted by sam

Stem cells have been touted as treatments for everything from hair loss to heart disease.

But are those claims scientifically sound?

Research on the technology continues to look promising, but many of its human applications are still preliminary and their effectiveness anecdotal.

Samumed, a $12 billion biotech start-up based in San Diego, profiled this month in Business Insider, exemplifies both sides of the coin.

The company has promised a bevy of age-reversing cures, including regrowing hair, treating wrinkles, and regenerating cartilage in people with osteoarthritis

However, their research isnt conclusive.

None of their treatments have received government approval yet.

Read more: Rheumatoid arthritis and stem cell treatments

Its easy to get excited about all this research.

Samumed Is Trying to Create the Fountain of Youth, says one headline.

Samumed Aims to Reverse Aging with Eternal Youth Treatments, says another.

Combined with $300 million in investment funding, the company has more than just buzz going for it in the biotech industry.

Their treatment for androgenetic alopecia (hair loss) is currently in phase II trials.

Its program to help people with osteoarthritis regrow cartilage in their knees is in phase III.

In total, the company has seven drugs in phase II trials, with plans to expand into more areas of disease research this year.

However, Samumed has raised some eyebrows in the industry with its secrecy. Some skeptics have likened the company to Theranos, a biotech start-up that was valued at $9 billion before an investigation by the Wall Street Journal led to a shutdown of the companys labs.

Samumed has been more open about presenting their data to the public but not about the actual treatments.

We're basically telling everyone, here's proof that it works, Samumed Chief Executive Officer, Osman Kibar, told Business Insider. How it works you just need to wait a little longer because we want to build as much of a head start as we can.

Read more: Stem cell treatments for multiple sclerosis

Beyond the applications of stem cells at Samumed, the technology is also being used to treat some of the United States most widespread health issues.

New research from the American Heart Association this month demonstrated the effectiveness of implanted stem cells into the hearts of people with cardiomyopathy.

Although the sample size was small (only 27 people), scientists noted function and symptomatic improvements of heart functioning as well as less frequency of hospitalization and lower medical costs. They conclude that the stem cell procedure is a feasible treatment for cardiomyopathy, but they note that a larger clinical follow-up is needed for more conclusive results.

In the past week, Newsweek reported on miracle stem cell treatments for burn victims that will promote healing without scars.

Stat News wrote about research on stem cells in mice that could potentially help cure Parkinsons disease.

Read more: Unproved stem cell treatments offer hope and risk

Some researchers in the industry are somewhat measured in their optimism of the technologys human applications.

I want to make sure that we provide a real cautionary note, especially to those individuals and those institutions that tout stem cells as the panacea for any ill, Dr. Cato Laurencin, director of the Institute for Regenerative Engineering at the University of Connecticut, told Healthline.

Laurencin, a medical practitioner at the forefront of stem cell technology, is a firm believer in the benefits of the treatment, but also remains skeptical of some of the claims associated with it.

Much of the evidence is still preliminary or anecdotal, and when people operate on information that is preliminary or anecdotal, there is the possibility for harm, he said.

His work in regenerative engineering a term he coined several years ago looks at the healing properties of implanted stem cells in the human body.

In research published this month, Laurencin and his team concluded that stem cells effectively improved healing to torn rotator cuff tendons in rats.

Rotator cuff tendon tears are a relatively common injury in humans and can be difficult to treat.

Unlike other tendons in the body, the rotator cuff tendon is unable to heal itself, said Laurencin.

Once it is torn, it is liable to be reinjured again and again.

However, the research released this month is about more than just applying stem cells to a certain kind of injury, its about how the stem cells are applied.

Read more: Scientists use 3-D environment to speed up growth of stem cells

Laurencin describes his field as an evolution of earlier work from 30 years ago in tissue engineering: a convergence of bringing together new technologies to create new science and new possibilities.

In this case, nanotechnology is at the heart of this stem cell operation.

Currently there are a variety of ways that stem cells can be implanted into a subject, including injections and bone marrow transplants.

For his research, Laurencin and his team used biomaterial based fiber matrices a nanomaterial conducive to growing and attaching stem cells to implant into the wounded area.

The results are promising, but Laurencin and his team will have to continue working with animals for some time before the process can be applied to humans.

The key is in understanding that stem cells have the potential for more than just regrowing damaged parts of the body.

The way we commonly think about a stem cell is it becoming a new tissue. But were also understanding that the stem cell itself can secrete biological factors that help regeneration occur. Thats what we think is happening here, said Laurencin.

His research into stem cells as a medicinal element in the body could have far reaching implications for all kinds of wound therapy.

Despite his measured approach, Laurencin is still willing to hypothesize about the excitement that the future of the field undoubtedly holds with proper time, funding, and research.

There are newts and salamanders that can regenerate a limb, he told Healthline.

How do we harness the cues that are taking place in these types of animals, and can we utilize what weve learned from these types of animals in humans?

Read more from the original source:
Stem Cell Research Advancing Rapidly - Healthline

Recommendation and review posted by simmons

TERT Identifiers Aliases TERT, CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1, TP2, TRT, hEST2, hTRT, telomerase reverse transcriptase External IDs OMIM: 187270 MGI: 1202709 HomoloGene: 31141 GeneCards: TERT Genetically Related Diseases breast cancer, interstitial lung disease, adenocarcinoma of the lung, prostate cancer, se atraganto con un caramelo, testicular germ cell cancer, idiopathic pulmonary fibrosis, malignant glioma[1] RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez Ensembl UniProt RefSeq (mRNA) RefSeq (protein) Location (UCSC) Chr 5: 1.25 1.3 Mb Chr 13: 73.63 73.65 Mb PubMed search [2] [3] Wikidata View/Edit Human View/Edit Mouse

Telomerase reverse transcriptase (abbreviated to TERT, or hTERT in humans) is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex.[4][5]

Telomerases are part of a distinct subgroup of RNA-dependent polymerases. Telomerase lengthens telomeres in DNA strands, thereby allowing senescent cells that would otherwise become postmitotic and undergo apoptosis to exceed the Hayflick limit and become potentially immortal, as is often the case with cancerous cells. To be specific, TERT is responsible for catalyzing the addition of nucleotides in a TTAGGG sequence to the ends of a chromosomes telomeres.[6] This addition of repetitive DNA sequences prevents degradation of the chromosomal ends following multiple rounds of replication.[7]

hTERT absence (usually as a result of a chromosomal mutation) is associated with the disorder Cri du chat.[8][9]

Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component that serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells, resulting in progressive shortening of telomeres. Studies in mice suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity.[10]

The hTERT gene, located on chromosome 5, consists of 16 exons and 15 introns spanning 35 kb. The core promoter of hTERT includes 330 base pairs upstream of the translation start site (AUG since it's RNA by using the words "exons" and "introns"), as well as 37 base pairs of exon 2 of the hTERT gene.[11][12][13] The hTERT promoter is GC-rich and lacks TATA and CAAT boxes but contains many sites for several transcription factors giving indication of a high level of regulation by multiple factors in many cellular contexts.[11] Transcription factors that can activate hTERT include many oncogenes (cancer-causing genes) such as c-Myc, Sp1, HIF-1, AP2, and many more, while many cancer suppressing genes such as p53, WT1, and Menin produce factors that suppress hTERT activity .[13][14] Another form of up-regulation is through demethylation of histones proximal to the promoter region, imitating the low density of trimethylated histones seen in embryonic stem cells.[15] This allows for the recruitment of histone acetyltransferase (HAT) to unwind the sequence allowing for transcription of the gene.[14]

Telomere deficiency is often linked to aging, cancers and the conditions dyskeratosis congenita (DKC) and Cri du chat. Meanwhile, over-expression of hTERT is often associated with cancers and tumor formation.[8][16][17][18] The regulation of hTERT is extremely important to the maintenance of stem and cancer cells and can be used in multiple ways in the field of regenerative medicine.

hTERT is often up-regulated in cells that divide rapidly, including both embryonic stem cells and adult stem cells.[17] It elongates the telomeres of stem cells, which, as a consequence, increases the lifespan of the stem cells by allowing for indefinite division without shortening of telomeres. Therefore, it is responsible for the self-renewal properties of stem cells. Telomerase are found specifically to target shorter telomere over longer telomere, due to various regulatory mechanisms inside the cells that reduce the affinity of telomerase to longer telomeres. This preferential affinity maintains a balance within the cell such that the telomeres are of sufficient length for their function and yet, at the same time, not contribute to aberrant telomere elongation [19]

High expression of hTERT is also often used as a landmark for pluripotency and multipotency state of embryonic and adult stem cells. Over-expression of hTERT was found to immortalize certain cell types as well as impart different interesting properties to different stem cells.[13][20]

hTERT immortalizes various normal cells in culture, thereby endowing the self-renewal properties of stem cells to non-stem cell cultures.[13][21] There are multiple ways in which immortalization of non-stem cells can be achieved, one of which being via the introduction of hTERT into the cells. Differentiated cells often express hTERC and TP1, a telomerase-associated protein that helps form the telomerase assembly, but does not express hTERT. Hence, hTERT acts as the limiting factor for telomerase activity in differentiated cells [13][22] However, with hTERT over-expression, active telomerase can be formed in differentiated cells. This method has been used to immortalize prostate epithelial and stromal-derived cells, which are typically difficult to culture in vitro. hTERT introduction allows in vitro culture of these cells and available for possible future research. hTERT introduction have an advantage over the use of viral protein for immortalization in that it does not involve the inactivation of tumor suppressor gene, which might lead to cancer formation.[21]

Over-expression of hTERT in stem cells changes the properties of the cells.[20][23][24] hTERT over-expression increases the stem cell properties of human mesenchymal stem cells. The expression profile of mesenchymal stem cells converges towards embryonic stem cells, suggesting that these cells may have embryonic stem cell-like properties. However, it has been observed that mesenchymal stem cells undergo decreased levels of spontaneous differentiation.[20] This suggests that the differentiation capacity of adult stem cells may be dependent on telomerase activities. Therefore, over-expression of hTERT, which is akin to increasing telomerase activities, may create adult stem cells with a larger capacity for differentiation and hence, a larger capacity for treatment.

Increasing the telomerase activities in stem cells gives different effects depending on the intrinsic nature of the different types of stem cells.[17] Hence, not all stem cells will have increased stem-cell properties. For example, research has shown that telomerase can be upregulated in CD34+ Umbilical Cord Blood Cells through hTERT over-expression. The survival of these stem cells was enhanced, although there was no increase in the amount of population doubling.[24]

Deregulation of telomerase expression in somatic cells may be involved in oncogenesis.[10]

Genome-wide association studies suggest TERT is a susceptibility gene for development of many cancers,[25] including lung cancer.[26]

Telomerase activity is associated with the number of times a cell can divide playing an important role in the immortality of cell lines, such as cancer cells. The enzyme complex acts through the addition of telomeric repeats to the ends of chromosomal DNA. This generates immortal cancer cells.[27] In fact, there is a strong correlation between telomerase activity and malignant tumors or cancerous cell lines.[28] Not all types of human cancer have increased telomerase activity. 90% of cancers are characterized by increased telomerase activity.[28]Lung cancer is the most well characterized type of cancer associated with telomerase.[29] There is a lack of substantial telomerase activity in some cell types such as primary human fibroblasts, which become senescent after about 3050 population doublings.[28] There is also evidence that telomerase activity is increased in tissues, such as germ cell lines, that are self-renewing. Normal somatic cells, on the other hand, do not have detectable telomerase activity.[30] Since the catalytic component of telomerase is its reverse transcriptase, hTERT, and the RNA component hTERC, hTERT is an important gene to investigate in terms of cancer and tumorigenesis.

The hTERT gene has been examined for mutations and their association with the risk of contracting cancer. Over two hundred combinations of hTERT polymorphisms and cancer development have been found.[29] There were several different types of cancer involved, and the strength of the correlation between the polymorphism and developing cancer varied from weak to strong.[29] The regulation of hTERT has also been researched to determine possible mechanisms of telomerase activation in cancer cells. Glycogen synthase kinase 3 (GSK3) seems to be over-expressed in most cancer cells.[27] GSK3 is involved in promoter activation through controlling a network of transcription factors.[27]Leptin is also involved in increasing mRNA expression of hTERT via signal transducer and activation of transcription 3 (STAT3), proposing a mechanism for increased cancer incidence in obese individuals.[27] There are several other regulatory mechanisms that are altered or aberrant in cancer cells, including the Ras signaling pathway and other transcriptional regulators.[27]Phosphorylation is also a key process of post-transcriptional modification that regulates mRNA expression and cellular localization.[27] Clearly, there are many regulatory mechanisms of activation and repression of hTERT and telomerase activity in the cell, providing methods of immortalization in cancer cells.

If increased telomerase activity is associated with malignancy, then possible cancer treatments could involve inhibiting its catalytic component, hTERT, to reduce the enzymes activity and cause cell death. Since normal somatic cells do not express TERT, telomerase inhibition in cancer cells can cause senescence and apoptosis without affecting normal human cells.[27] It has been found that dominant-negative mutants of hTERT could reduce telomerase activity within the cell.[28] This led to apoptosis and cell death in cells with short telomere lengths, a promising result for cancer treatment.[28] Although cells with long telomeres did not experience apoptosis, they developed mortal characteristics and underwent telomere shortening.[28] Telomerase activity has also been found to be inhibited by phytochemicals such as isoprenoids, genistein, curcumin, etc.[27] These chemicals play a role in inhibiting the mTOR pathway via down-regulation of phosphorylation.[27] The mTOR pathway is very important in regulating protein synthesis and it interacts with telomerase to increase its expression.[27] Several other chemicals have been found to inhibit telomerase activity and are currently being tested as potential clinical treatment options such as nucleoside analogues, retinoic acid derivatives, quinolone antibiotics, and catechin derivatives.[30] There are also other molecular genetic-based methods of inhibiting telomerase, such as antisense therapy and RNA interference.[30]

hTERT peptide fragments have been shown to induce a cytotoxic T-cell reaction against telomerase-positive tumor cells in vitro.[31] The response is mediated by dendritic cells, which can display hTERT-associated antigens on MHC class I and II receptors following adenoviral transduction of an hTERT plasmid into dendritic cells, which mediate T-cell responses.[32] Dendritic cells are then able to present telomerase-associated antigens even with undetectable amounts of telomerase activity, as long as the hTERT plasmid is present.[33]Immunotherapy against telomerase-positive tumor cells is a promising field in cancer research that has been shown to be effective in in vitro and mouse model studies.[34]

Induced pluripotent stem cells (iPS cells) are somatic cells that have been reprogrammed into a stem cell-like state by the introduction of four factors (Oct3/4, Sox2, Klf4, and c-Myc).[35] iPS cells have the ability to self-renew indefinitely and contribute to all three germ layers when implanted into a blastocyst or use in teratoma formation.[35]

Early development of iPS cell lines were not efficient, as they yielded up to 5% of somatic cells successfully reprogrammed into a stem cell-like state.[36] By using immortalized somatic cells (differentiated cells with hTERT upregulated), iPS cell reprogramming was increased by twentyfold compared to reprogramming using mortal cells.[36]

The reactivation of hTERT, and subsequently telomerase, in human iPS cells has been used as an indication of pluripotency and reprogramming to an ES (embryonic stem) cell-like state when using mortal cells.[35] Reprogrammed cells that do not express sufficient hTERT levels enter a quiescent state following a number of replications depending on the length of the telomeres while maintaining stem cell-like abilities to differentiate.[36] Reactivation of TERT activity can be achieved using only three of the four reprogramming factors described by Takahashi and Yamanaka: To be specific, Oct3/4, Sox2 and Klf4 are essential, whereas c-Myc is not.[15] However, this study was done with cells containing endogenous levels of c-Myc that may have been sufficient for reprogramming.

Telomere length in healthy adult cells elongates and acquires epigenetic characteristics similar to those of ES cells when reprogrammed as iPS cells. Some epigenetic characteristics of ES cells include a low density of tri-methylated histones H3K9 and H4K20 at telomeres, as well as an increased detectable amount of TERT transcripts and protein activity.[15] Without the restoration of TERT and associated telomerase proteins, the efficiency of iPS cells would be drastically reduced. iPS cells would also lose the ability to self-renew and would eventually senesce.[15]

DKC (dyskeratosis congenita) patients are all characterized by the defective maintenance of telomeres leading to problems with stem cell regeneration.[16] iPS cells derived from DKC patients with a heterozygous mutation on the TERT gene display a 50% reduction in telomerase activity compared to wild type iPS cells.[37] Conversely, mutations on the TERC gene (RNA portion of telomerase complex) can be overcome by up-regulation due to reprogramming as long as the hTERT gene is intact and functional.[38] Lastly, iPS cells generated with DKC cells with a mutated dyskerin (DKC1) gene cannot assemble the hTERT/RNA complex and thus do not have functional telomerase.[37]

The functionality and efficiency of a reprogrammed iPS cell is determined by the ability of the cell to re-activate the telomerase complex and elongate its telomeres allowing for self-renewal. hTERT is a major limiting component of the telomerase complex and a deficiency of intact hTERT impedes the activity of telomerase, making iPS cells an unsuitable pathway towards therapy for telomere-deficient disorders.[37]

Although the mechanism is not fully understood, exposure of TERT-deficient hematopoietic cells to androgens resulted in an increased level of TERT activity.[39] Cells with a heterozygous TERT mutation, like those in DKC (dyskeratosis congenita) patients, which normally exhibit low baseline levels of TERT, could be restored to normal levels comparable to control cells. TERT mRNA levels are also increased with exposure to androgens.[39] Androgen therapy may become a suitable method for treating circulatory ailments such as bone marrow degeneration and low blood count linked with DKC and other telomerase-deficient conditions.[39]

As organisms age and cells proliferate, telomeres shorten with each round of replication. Cells restricted to a specific lineage are capable of division only a set number of times, set by the length of telomeres, before they senesce.[40] Depletion and uncapping of telomeres has been linked to organ degeneration, failure, and fibrosis due to progenitors' becoming quiescent and unable to differentiate.[19][40] Using an in vivo TERT deficient mouse model, reactivation of the TERT gene in quiescent populations in multiple organs reactivated telomerase and restored the cells abilities to differentiate.[41] Reactivation of TERT down-regulates DNA damage signals associated with cellular mitotic checkpoints allowing for proliferation and elimination of a degenerative phenotype.[41] In another study, introducing the TERT gene into healthy one-year-old mice using an engineered adeno-associated virus led to a 24% increase in lifespan, without any increase in cancer.[42]

The hTERT gene has become a main focus for gene therapy involving cancer due to its expression in tumor cells but not somatic adult cells.[43] One method is to prevent the translation of hTERT mRNA through the introduction of siRNA, which are complimentary sequences that bind to the mRNA preventing processing of the gene post transcription.[44] This method does not completely eliminate telomerase activity, but it does lower telomerase activity and levels of hTERT mRNA seen in the cytoplasm.[44] Higher success rates were seen in vitro when combining the use of antisense hTERT sequences with the introduction of a tumor-suppressing plasmid by adenovirus infection such as PTEN.[45]

Another method that has been studied is manipulating the hTERT promoter to induce apoptosis in tumor cells. Plasmid DNA sequences can be manufactured using the hTERT promoter followed by genes encoding for specific proteins. The protein can be a toxin, an apoptotic factor, or a viral protein. Toxins such as diphtheria toxin interfere with cellular processes and eventually induce apoptosis.[43] Apoptotic death factors like FADD (Fas-Associated protein with Death Domain) can be used to force cells expressing hTERT to undergo apoptosis.[46] Viral proteins like viral thymidine kinase can be used for specific targeting of a drug.[47] By introducing a prodrug only activated by the viral enzyme, specific targeting of cells expressing hTERT can be achieved.[47] By using the hTERT promoter, only cells expressing hTERT will be affected and allows for specific targeting of tumor cells.[43][46][47]

Aside from cancer therapies, the hTERT gene has been used to promote the growth of hair follicles.[48]

A schematic animation for gene therapy is shown as follows.

Telomerase reverse transcriptase has been shown to interact with:

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Telomerase reverse transcriptase - Wikipedia

Recommendation and review posted by simmons

Having worked at University Malaya Medical Centres (UMMC) Paediatrics Department for 20 years, senior consultant paediatric oncologist Prof Dr Hany Mohd Ariffin has had to tell her fair share of parents that there is nothing more that can be done for their terminally ill child.

As head of the Paediatric Haematology-Oncology and Bone Marrow Transplantation Unit, this is usually because there is no suitable donor available for a life-saving bone marrow transplant for the child.

Bone marrow transplants, also called stem cell transplants, are used in conditions where the patients bone marrow is damaged or destroyed by disease or intensive cancer treatment, and is unable to carry out its job of producing healthy red blood cells, white blood cells and platelets.

Because white blood cells or leukocytes are part of the immune system that protects our body against foreign invaders, it is critical in such a procedure to match the so-called immunological fingerprints of the patient and the donor.

As Prof Hany explains, these fingerprints are known as human leukocyte antigens (HLAs).

HLAs help the immune system distinguish between the bodys own cells and foreign cells, usually bacteria and viruses that infect us, so that our white blood cells can find and destroy them.

It is crucial that a bone marrow donor and the patient have the same HLAs in order to minimise the chances of the donated bone marrows white blood cells considering its new host body as foreign and attacking it.

Perfect match needed

Standard bone marrow transplantations require that all 10 HLAs in both patient and donor are a match.

As HLAs are inherited half from each parent, this means that only a patients siblings are a possible perfect match.

Explains Prof Hany: If you look at statistics, out of four, one sibling will be completely matched, one sibling will be completely not matched, and two siblings would be half-matched.

So, the chances of finding a match is 25%, but that is statistical randomisation.

In the real world, you can have 10 siblings and all of them might not be matched with you.

If a patient does not have a sibling that matches perfectly with them, or does not have a sibling at all, their only other option is to check for an unrelated match in international stem cell registries or blood banks.

However, Prof Hany notes that this usually requires a sum of RM100,000 for a unit of bone marrow and at least three to four months of waiting two luxuries not all patients have.

She adds: But it is not easy to get a good match for Asians as these registries are usually Caucasian.

And its even worse if you are an Indian patient, as you cant even go to a Taiwanese blood bank.

In the case of Muhammad Yusuff Iskandar Mohd Hambali, time was a critical factor.

The firstborn of two teachers had been referred to UMMC at 10 months of age for recurrent pneumonia.

His mother, secondary school physical education teacher, Aduratun Nasyihin Mokhtar shares: He started falling sick at the age of seven months he had a persistent cough.

Initially, the doctor thought it was pertussis, but it didnt get better after three months as pertussis should, so he was admitted to the hospital.

However, none of the antibiotics they tried worked, so he was referred to UMMC to check his lungs.

This filepic shows a thalassaemia patient with his infusion pump machine for iron-chelating therapy. Thalassaemia is one of the conditions curable by a bone marrow transplant.

It was in UMMC that Yusuff, as he is called, was discovered to have X-linked severe combined immunodeficiency (SCID).

This rare genetic condition, also known as bubble boy disease, results in the malfunction or lack of two specialised white blood cells called T and B cell lymphocytes.

This means that Yusuff effectively had a non-existent immune system.

This was the reason he could not fight off the pneumonia. In fact, his lungs had deteriorated so badly that he was on oxygen therapy from the age of eight months.

In addition, the Mycobacterium bovis in his BCG vaccination had spread to his back, he had chronic diarrhoea and he was very much underweight.

Yusuff needed a bone marrow transplant, and he needed it fast.

Having reached out to her international colleagues at that time, Prof Hany says: One thing constant in all their advice was that if we delayed the procedure, he would never get better from his disseminated BCG, his pneumonia would just worsen, and once you reach a critical point, there would be no turning back.

He would have been dead by six months.

The problem was that Yusuff was then an only child.

Although his mother was pregnant with his younger sister at that time, she would not have been born in time to help him, assuming that she was a match for him in the first place.

With no time to waste, Prof Hany and her team decided to try a procedure called haplo-identical bone marrow transplantation.

On whether she and her team were ready to carry out the new procedure, Prof Hany says that you will never be ready until a life is dangling precariously in front of you. Photo: The Star/Samuel Ong

In this procedure, only five out of 10 HLAs need to be matched in order for the donor to be able to give bone marrow to the patient.

The beauty of this procedure is that you always have two parents (to donate), says Prof Hany.

So, Yusuffs father, sports science and physical education teacher Mohd Hambali Din @ Ismail, could now donate his bone marrow cells to his son.

First though, Yusuff needed to be fattened up via nutritional fluids infused into his veins, his pneumonia brought under control and his M. bovis infection treated with anti-tuberculosis therapy.

This was so that he would be in a decent enough condition to withstand the procedure.

Following the protocol established by Johns Hopkins University in the United States, but modified to suit Yusuffs condition, Prof Hany and her team first killed off Yusuffs remaining bone marrow cells through chemothera-py, before infusing 30ml of his fathers donated bone marrow into him.

Prof Hany explains that it takes two to three weeks for the new bone marrow cells to grow, during which time the patient is completely vulnerable to any infection.

This is why they remain in a completely sealed room where the air is hepa-filtered, they receive no visitors, and their food and linen are completely sterile, she says.

He was also treated with high-dose cyclophosphamide, a chemotherapy drug that targets T cell lymphocytes.

This was in order to destroy the half-matched mature T cells that came with his fathers donated bone marrow.

T cells are your soldier cells. His fathers T cells would recognise Yusuff as foreign and destroy everything in their wake.

And that is what has precluded mismatched transplants all this while, explains Prof Hany.

After the mature T cells are destroyed, she says: What you then get are T cells from stem cell origin, which learn to tolerate the environment of being in Yusuffs body, and therefore, they will be less aggressive and more friendly to these cells that they consider foreign.

Despite that, Yusuff still experienced graft-versus-host disease (GvHD) where his new white blood cells attacked the cells of his skin, gut and lungs.

In between, he also had two episodes of sepsis and he had to go to the ICU once.

He also had to go on the ventilator at one point, says Prof Hany.

She explains that GvHD, which is due to aggressive donor white blood cells, and infections, which are due to the still incomplete immune system, can co-exist, creating a dilemma for the medical team.

On the one hand, to ameliorate GvHD, you have to give steroids (in addition to standard immunosuppresants) to dampen down the immune system.

You dampen down the immune system, then you allow bacteria and fungi to grow.

And that is why it is very challenging, she says.

She admits: For the first 20 days, it was all very smooth and you think, Wah, Im a hero, but then the challenges came.

There were certain moments when I thought, Thats it, were going to lose him.

It took 149 days after the transplant before Yusuff was deemed well enough to be sent home.

And it was one year before Prof Hany and her team felt confident enough to declare him cured.

We estimate anything between six months to a year for the new bone marrow cells to grow and propagate.

So usually, after a year, if the GvHD doesnt appear anymore, it is very unlikely to suddenly appear, she explains.

This first anniversary of Yusuffs transplant, celebrated at UMMC on April 6, was not just sweet because of Yusuffs survival, it was also the opening of a new path for Prof Hany and her team.

On a personal note, there were many times when you have this period of self-doubt.

So, you think that we are just a bunch of stupid, gung-ho people, who are unrealistic; this is not America, this cannot be done that sort of feeling.

There were some moments when you think, have I done a disservice to this child? Would if it have been better to just let go, for the parents to just let go? Is God just testing me? shares Prof Hany.

However, a few months after Yusuffs transplant, she received the case of a baby boy with myelodysplastic syndrome.

Myelodysplastic children will progress to develop acute myeloid leukaemia within a year, and it is only curable with transplant, or not it is certain death by two years, she explains.

And this patient had two siblings, both of whom were only half-matched.

But we were able to offer a transplant to this child, because we knew that from the experience of Yusuff, if he has very bad GvHD of the gut, skin, lung, we would be able to handle it been there, done that.

We were already scarred for life, she says with a laugh. And in fact, due to their prior experience, Prof Hany and her team were able to more precisely determine the amount of donated bone marrow cells needed for transplant.

As a result, she says: The second patient sailed through and was discharged after only five weeks, as opposed to five months for Yusuff.

Explaining the potential impact of having this treatment option available, Prof Hany shares that bone marrow transplantation is a cure for conditions like leukaemia, blood disorders like thalassaemia, congenital defective immune systems and certain rare congenital metabolic conditions.

The major reason why transplants are not being done is because of the lack of an available donor, she says.

But haplo-identical bone marrow transplantation now opens the way for many more potential donors to help the patient.

The learning curve is steep, Prof Hany admits, but adds that after Yusuff, they were able to apply what they learnt to their second patient with great effect.

Im not saying it is easy, but I think it is worth developing further, because it can solve one of the greatest health problems in our country, which is inherited blood disorders.

Giving the example of thalassaemia, she estimates that it costs some RM3.5mil to treat a patient with regular blood transfusions and iron-chelating therapy for 30 years.

A haplo-identical bone marrow transplant costs approximately RM45,000 and will cure the patient.

The risk of dying from this procedure usually because of infections and GvHD during the period when the patient has no working immune system is estimated to be about 10%.

This is at the upper limit for standard bone marrow transplants, where the risk ranges from 5% to 10%.

She adds that studies have shown that the risk of severe GvHD is similar for haplo-identical transplants and sibling-matched transplants, which are both lower than transplants from an unrelated donor.

Although Yusuff is the first successful haplo-identical bone marrow transplant patient in the country, to the best of Prof Hanys knowledge, she believes that the procedure can be easily done in other major hospitals around the country.

The facilities are already there and specialists trained in bone marrow transplants need only learn the procedure once before they should be able to conduct it, she says.

So its not just having a big celebration to tell the world that we saved one boy with SCID, its having the ability to tell parents that there is always hope, as we can now do haplo-identical transplants in our centre, says Prof Hany.

It is about no longer having to tell parents that nothing more can be done for their terminally ill child.

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New hope with haplo-identical bone marrow transplant - Star2.com

Recommendation and review posted by sam

Salk Institute and Chinese researchers report creating a new kind of stem cell, one that is more versatile than any other normally grown in the lab.

Called an extended pluripotent stem cell, it can give rise to every cell type in the body, the researchers say in a recent study. This includes the extra-embryonic tissues such as the placenta that support the developing baby. Just one cell can generate a complete organism.

Embryonic stem cells and artificial embryonic stem cells called induced pluripotent stem cells cant make these extra-embryonic tissues. So neither embryonic nor IPS cells can give rise to a complete embryo, because the supportive tissues necessary for an embryo to survive arent there.

But the extended pluripotent stem cells can reliably give rise to both types of cells, and thus whole embryos and offspring, the scientists report.

The EPS cells were made from human and mouse embryonic stem cells. In addition, they were produced from skin cells, or fibroblasts by treating them with a chemical cocktail. IPS cells, invented in 2006, are generated from fibroblasts by a similar reprogramming process.

To demonstrate this ability to make all cell types, the researchers grew an entire mouse from just one EPS cell. They also grew chimeric mice, with human EPS cells integrating into the mice better than embryonic stem cells did.

The study on these new stem cells was published April 6 in the journal Cell. It can be found at j.mp/extendedstem.

Better tool

That characteristic of creating every cell in the body, called totipotency, is normally found only at the very beginning of embryonic development. Embryonic stem cells are usually extracted too late, when the cells have already divided into the embryonic and extra-embryonic lineages.

Totipotent stem cells have been observed in the lab, but they lasted briefly, and didnt yield stable totipotent cell lines.

Salk Institute stem cell researcher Juan Carlos Izpisa Bemonte was a cosenior author of the paper along with Hongkui Deng of Peking University in Beijing. The first authors were Yang Yang, Bei Liu, Jun Xu, and Jinlin Wang; all of Peking University, and Jun Wu, of the Salk Institute.

EPS cell lines provide a useful cellular tool for gaining a better molecular understanding of initial cell fate commitments and generating new animal models to investigate basic questions concerning development of the placenta, yolk sac, and embryo proper, the study stated.

Furthermore, they also provide an unlimited cell resource and hold great potential for in vivo disease modeling, in vivo drug discovery, and in vivo tissue generation in the future. Finally, our study opens a path toward capturing stem cells with intra- and/or inter-species bi-potent chimeric competency from a variety of other mammalian species.

Organs for transplant

The creation of chimeric mice is part of Izpisa Bemontes longstanding goal of growing human organs in animals for transplant.

While mice are too small to grow organs for transplant, they serve as a model to understand how cells from a different species, can be grown in a host body. In this new study, the mice served as a model of how well the EPS cells can integrate.

Izpisa Bemonte is now working to translate his research on chimeric mice to pigs, which are large enough to provide human organs. In January, a team he led reported on work with human-pig chimeras, which were not allowed to grow past the embryonic stage. They also created rat-mice chimeras.

The superior chimeric competency of both human and mouse EPS cells is advantageous in applications such as the generation of transgenic animal models and the production of replacement organs, Wu said in a Salk statement. We are now testing to see whether human EPS cells are more efficient in chimeric contribution to pigs, whose organ size and physiology are closer to humans.

We believe that the derivation of a stable stem cell line with totipotent-like features will have a broad and resounding impact on the stem cell field, Izpisua Belmonte said in the statement.

The work was funded by a number of sources. They include: the National Key Research and Development Program of China; the National Natural Science Foundation of China; the Guangdong Innovative and Entrepreneurial Research Team Program; the Science and Technology Planning Project of Guangdong Province, China; the Science and Technology Program of Guangzhou, China; the Ministry of Education of China (111 Project); the BeiHao Stem Cell and Q9 Regenerative Medicine Translational Research Institute; the Joint Institute of Peking University Health Science Center; University of Michigan Health System; Peking-Tsinghua Center for Life Sciences; the National Science and Technology Support Project; the CAS Key Technology Talent Program; the G. Harold and Leila Y. Mathers Charitable Foundation; and The Moxie Foundation.

bradley.fikes@sduniontribune.com

(619) 293-1020

Continued here:
Stem cell invented that can grow into any tissue in the body - The San Diego Union-Tribune

Recommendation and review posted by simmons

This report, Male Hypogonadism - Pipeline Review, H2 2016, provides an overview of the Male Hypogonadism pipeline landscape.

The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases.

Additionally, the report provides an overview of key players involved in therapeutic development for Male Hypogonadism and features dormant and discontinued projects.

This report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data and information sourced from This report proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources.

Drug profiles featured in the report undergoes periodic review following a stringent set of processes to ensure that all the profiles are updated with the latest set of information. Additionally, various dynamic tracking processes ensure that the most recent developments are captured on a real time basis.

The report helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage.

Accessthis report @ http://www.htfmarketreport.com/buy-now?format=1&report=138812

Scope

- The report provides a snapshot of the global therapeutic landscape of Male Hypogonadism

- The report reviews pipeline therapeutics for Male Hypogonadism by companies and universities/research institutes based on information derived from company and industry-specific sources

- The report covers pipeline products based on various stages of development ranging from pre-registration till discovery and undisclosed stages

- The report features descriptive drug profiles for the pipeline products which includes, product description, descriptive MoA, R&D brief, licensing and collaboration details & other developmental activities

- The report reviews key players involved Male Hypogonadism therapeutics and enlists all their major and minor projects

- The report assesses Male Hypogonadism therapeutics based on drug target, mechanism of action (MoA), route of administration (RoA) and molecule type

- The report summarizes all the dormant and discontinued pipeline projects

- The report reviews latest news related to pipeline therapeutics for Male Hypogonadism

Reasons to access

- Gain strategically significant competitor information, analysis, and insights to formulate effective R&D strategies

- Identify emerging players with potentially strong product portfolio and create effective counter-strategies to gain competitive advantage

- Identify and understand important and diverse types of therapeutics under development for Male Hypogonadism

- Identify potential new clients or partners in the target demographic

- Develop strategic initiatives by understanding the focus areas of leading companies

- Plan mergers and acquisitions effectively by identifying key players and its most promising pipeline therapeutics

- Devise corrective measures for pipeline projects by understanding Male Hypogonadism pipeline depth and focus of Indication therapeutics

- Develop and design in-licensing and out-licensing strategies by identifying prospective partners with the most attractive projects to enhance and expand business potential and scope

- Modify the therapeutic portfolio by identifying discontinued projects and understanding the factors that drove them from pipeline

Make an enquiry on this Report @ http://www.htfmarketreport.com/enquiry-before-buy/138812-male-hypogonadism-pipeline-review-3

Table of Contents

List of Tables 6

List of Figures 7

Introduction 8

Global Markets Direct Report Coverage 8

Male Hypogonadism Overview 9

Therapeutics Development 10

Pipeline Products for Male Hypogonadism - Overview 10

Pipeline Products for Male Hypogonadism - Comparative Analysis 11

Male Hypogonadism - Therapeutics under Development by Companies 12

Male Hypogonadism - Therapeutics under Investigation by Universities/Institutes 14

Male Hypogonadism - Pipeline Products Glance 15

Late Stage Products 15

Clinical Stage Products 16

Early Stage Products 17

Male Hypogonadism - Products under Development by Companies 18

Male Hypogonadism - Products under Investigation by Universities/Institutes 20

Male Hypogonadism - Companies Involved in Therapeutics Development 21

Antares Pharma, Inc. 21

Clarus Therapeutics, Inc. 22

Endo Pharmaceuticals Inc. 23

EndoCeutics, Inc. 24

Ferring International Center S.A. 25

Forendo Pharma Limited 26

Lipocine Inc. 27

M et P Pharma AG 28

Merck & Co., Inc. 29

Mereo Biopharma Group Plc 30

Millennium Pharmaceuticals Inc 31

Pantarhei Bioscience BV 32

Repros Therapeutics Inc. 33

Variant Pharmaceuticals, Inc. 34

Male Hypogonadism - Therapeutics Assessment 35

Assessment by Monotherapy Products 35

Assessment by Target 36

Assessment by Mechanism of Action 38

Assessment by Route of Administration 40

Assessment by Molecule Type 42

Drug Profiles 44

BGS-649 - Drug Profile 44

Product Description 44

Mechanism Of Action 44

R&D Progress 44

corifollitropin alfa - Drug Profile 45

Product Description 45

Mechanism Of Action 45

R&D Progress 45

enclomiphene citrate - Drug Profile 47

Product Description 47

Mechanism Of Action 47

R&D Progress 47

fispemifene - Drug Profile 58

.. Continued

Read Detailed Table of Content @ http://www.htfmarketreport.com/reports/138812-male-hypogonadism-pipeline-review-3

...

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Recent research: Male hypogonadism - strategic assessment and ... - WhaTech

Recommendation and review posted by Bethany Smith

WASHINGTON D.C: Scientists have developed a revolutionary 3D-bioprinted patch that could one day be used to repair damage to the human heart.

The patch can help heal scarred heart tissue after a heart attack. The discovery is a major step forward in treating patients with tissue damage after a heart attack.

The researchers from the University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

When the cell patch was placed on a mouse following a simulated heart attack, the researchers saw significant increase in functional capacity after just four weeks. Since the patch was made from cells and structural proteins native to the heart, it became part of the heart and absorbed into the body, requiring no further surgeries.

"This is a significant step forward in treating the No. 1 cause of death in the U.S.," said researcher Brenda Ogle. "We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years."

Ogle said that this research is different from previous research in that the patch is modelled after a digital, three-dimensional scan of the structural proteins of native heart tissue. The digital model is made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells. Only with 3D printing of this type can we achieve one micron resolution needed to mimic structures of native heart tissue.

"We were quite surprised by how well it worked given the complexity of the heart," Ogle noted. "We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch."

Ogle said they are already beginning the next step to develop a larger patch that they would test on a pig heart, which is similar in size to a human heart.

The research study is published in Circulation Research, a journal published by the American Heart Association.

Read more:
Breakthrough in cardiac health: 3D-printed patch can help mend a 'broken' heart - Economic Times

Recommendation and review posted by simmons

It would seem the beautiful foxglove plant has more uses than just the garden.

A novel drug screen in liver-like cells shows that cardiac glycosides, which are found in the leaves of the digitalis or foxglove plant, could reduce low-density lipoprotein (LDL) cholesterol differently than statins, potentially providing a new treatment for patients.

The foxglove plant in bloom on MUSC's campus.

These findings were reported by the Medical University of South Carolina researcher Stephen A. Duncan, D.Phil., SmartState Chair of Regenerative Medicine at MUSC, and colleagues in the April 6 issue of Cell Stem Cell.

Duncan said the glycosides were identified through a stem cell screen for compounds that could be used off-label for the treatment of high cholesterol. The nice thing about finding new uses for drugs already on the market is that they can be used relatively quickly in patients because most of the needed safety trials have already been completed.

Not everyone with high LDL cholesterol responds to statins. Statins increase levels of a cell surface receptor that removes LDL cholesterol from the bloodstream. However, statins do not work in patients with familial hypercholesterolemia (FH), who have a rare mutation in that receptor. It is an inherited disorder that leads to aggressive and premature cardiovascular disease. FH patients have very high cholesterol and can die of cardiovascular disease by their forties. The existing drugs for FH can cause fatty liver disease, and the best treatment is a liver transplant.

Duncan and his graduate student Max Cayo, who is finishing his M.D. at the Medical College of Wisconsin, developed a drug screen to identify an alternative to statins. Apolipoprotein B (apoB) is a molecule that liver cells use to make LDL. Drugs that decreased apoB could potentially lower cholesterol independently of the LDL receptor in FH patients and also in patients with other forms of high cholesterol.

FH was a perfect model for testing alternatives to statins. Yet the rarity of FH meant these liver cells were scarce. Duncans group made induced pluripotent stem cells out of skin fibroblasts taken from a single patient with FH. Stem cells continually double their numbers while in culture. This meant that a sample of converted skin cells from a single patient with FH provided a renewable source of liver-like cells that retained the mutation.

The group tested these liver-like cells with the SPECTRUM library, a collection of 2,300 pharmaceuticals, many of which have reached clinical trials. Surprisingly, all nine cardiac glycosides in the collection, some widely prescribed for heart failure, reduced apoB in liver-like cells from the patient with FH. In further tests, they also lowered apoB in human hepatocytes and in mice engineered to grow normal human livers without the FH mutation.

Next, the team combed through more than five thousand medical records of patients prescribed cardiac glycosides for heart failure who also had LDL cholesterol records. Similar drops in LDL levels were observed in these patients as in a matching group of patients prescribed statins.

This study provides the first evidence that cardiac glycosides could potentially reduce LDL cholesterol independently of the LDL receptor, where statins act, by reducing apoB.

The cardiac glycosides are always prescribed with care, as they are known to be toxic at high doses. However, they could offer inexpensive life-saving options for patients with FH. Additionally, a cardiac glycoside in a low dose could conceivably provide an added benefit to patients already taking a statin. Duncan is exploring plans for a clinical trial that would determine the correct dose in hypercholesterolemia patients.

Using patient stem cells to screen drugs that are already on the market is a great way to investigate treatments for liver diseases.

There are so few livers available for transplant, Duncan said. Having the stem cell model where we make liver cells in the culture dish opens up a possibility of using this not only to investigate a disease, but also as a way to discover drugs that could fix a disease.

This article has been republished frommaterialsprovided by theMedical University of South Carolina. Note: material may have been edited for length and content. For further information, please contact the cited source.

Excerpt from:
SPECTRUM Drug Screen Reveals Fox Gloves Can Treat High Cholesterol - Technology Networks

Recommendation and review posted by simmons

AGR bowler Cameron Hurwitz overcomes rare disease and keeps on bowling. Shawn Dowd

Cameron Hurwitz, freshman at Brighton High School, practices bowling Monday, April 10, 2017. Hurwitz is a two-time AGR bowler. (Photo: SHAWN DOWD/@sdowdphoto/, STAFF PHOTOGRAPHER)Buy Photo

When you think of tough athletes, football and hockey players quickly come to mind.

But a bowler?

Someone who learned that with determination and the love of family, friends, teammates and one anonymous bone marrow donor living 1,500 miles away striking down a rare and deadly blood disease is indeed possible?

Cameron Hurwitz stands 4-foot-11 and weighs 84 pounds with Skittles in his pockets.

But the Brighton High School freshman is a big man on the lanes, leading the Barons this season with a 216.5 average, making the coveted six-man state tournament composite team, where he led Section V to a third-place finish, and being named All-Greater Rochester for the second time in three seasons.

He has rolled three 300-games (two sanctioned) and just recently recorded a personal-best 799 series in competition.

There was a time when opponents sized up Hurwitz and took him for an easy mark. No more.

MEET:The 2016-17 AGR Boys Bowling Team

MEET:The 164 athletes who make up the 2016-17 Winter teams

Hes pretty well-known now, Brighton coach Jason Wasserman said. What they cant believe is thathes only in ninth grade and doing as well as he is. He reads lane conditions as good as anyone out there. Hes able to make adjustments on the fly, he knows what equipment to use at what time and then hes just so consistent with his shots.

Thats what happens when you bowl nearly every day from the time youre eye level to a ball rack. When you have parents, Caryn and Scott Hurwitz, who nurture your gifts with unconditional love. When a big brother, Reese, a senior on the Brighton team with a fine 210 average of his own and is headed to Purdue to bowl, is always there to cheer the strikes and help you handle the splits and open frames of life.

Cameron, 14, a hard-throwing right-hander, throws a ball that takes a sharp, last-second right-to-left hook into the pocket that makes pins explode like fireworks on the Fourth of July.

He has had many mentors but in large part he is a self-taught prodigy.

As a big PBA fan who would like to compete on tour someday, he has long watched bowling on television and the internet. He reads bowling magazines, studies the history of the gameand can recite the career statistics of PBA stars. His favorite player is a kindred spirit, 5-foot-5 Norm Duke, a family friend whose autograph he wears proudly on his green Storm bowling shirt.

For good measure, Cameron drills his own balls, customizes his own bowling shoes (blue and fluorescent green on this day), and has ideas for other bowling products that his dad, who owns a motorcycle parts manufacturing business, helps bring to life. Some have already caught the attention of people in the industry.

I think it came from watching the pros on television all the time and picking it up, Cameron said when asked where his style and passion for all things bowling comes from. I love all the physics behind bowling and just the fact you have to use your mind to be able to perform. Anybody of any size can be great at bowling as long as you know the right way to do it and as long as you know what each piece of equipment does for a particular oil pattern.

Bowling alone during off-hours, wearing a mask to prevent against infection, Cameron Hurwitz never gave up on dream of normal life and returning to Brighton High School team.(Photo: CARYN HURWITZ)

Understanding bowling science helped Cameron enjoy his best season so far, but it was medical science that got him back on the lanes.

A little more than two years ago while in the seventh grade, Cameron was getting ready to leave for the Section V tournament when his mother spotted black-and-blue marks on his arms and legs. A phone call to their family doctor led to blood work, which led to instructions to take her son to the emergency room immediately.

He had extremely low platelets, which clot your blood, and they told us to pack a bag, youll be there for many days, Caryn Hurwitz said.

It was six days to be exact, during which Cameron was diagnosed with Aplastic Anemia, a rare and serious blood disorder in which the body stops making enoughnew white and red cells and platelets.

His bone marrow had just shut down and with so few platelets he was at great risk, and with no immunity he couldnt be around people, Caryn Hurwitz said.

While undergoing treatments at Golisano Childrens Hospital, Cameron was unable to attend school and was quarantined at home for over five months. When given the OK by doctors, his lone escape was making trips to area bowling centers where generous owners allowed him to practice during off-hours to the public.

Encouraged by upticks in his white cell counts, Camerons caregivers couldnt say no when he begged to compete in the prestigious United States Bowling Congress Junior Gold national championships in the Chicago area in July 2015. While wearing an antiviral mask and in between receiving seven-hour blood transfusions at a Chicago hospital, Cameron made the televised final, placing second in the U12 division.

The boy behind the mask became a media celebrity and inspiration in the bowling community. He made the cover of Bowlers Journal and PBA stars became his fans. Hall of Famer Pete Weber posted a good luck video message on Facebook to Cameron.

Hed bowl without hardly any oxygen (in his bloodstream), Caryn Hurwitz said. I dont think people really understood how hard it was for him, but as long as he could go, even with the low blood counts, he kept bowling. When I think about, Im amazed.

Unfortunately for Cameron, the treatments he received didnt produce the desired results and as his eighth-grade school year began, he was placed on the national Be the Matchbone marrow registry.

Waiting times for a match can vary, but in Camerons case one was found in just a few months. And on Dec. 29, 2015 he underwent a transplant at Boston Childrens Hospital, a painstaking procedure where a patients body is re-started with new stem cells that need time to grow and take hold.

Six weeks in the hospital were followed by six more months of isolation, school tutoring, the entire Hurwitz family living in the germ-free lane, and the family bonding like an alleys glued wooden strips.

Throughout his recovery, Cameron kept bowling after hours, determined to be ready for his freshman season. Bowling had become his medicine.

So many gracious people had followed his story and said, When were closed come in and you just bowl, "Caryn Hurwitz said. He went in there and said Im just going to get stronger and do this. And he did.

Four months ago, on Camerons one-year checkup, the Hurwitzes received the news they prayed for: His blood counts were all near normal and he could resume living a normal life.

The mask went into the trash like an old pair of bowling shoes.

The feeling of freedom that you can go someplace and not have to wear a mask, it was awesome, Cameron said. For six months, I couldnt do anything. I could be anywhere outside but the only place inside I could be was at my home or the hospital.

He knew he was back the day he saw his hero, Norm Duke, in Columbus, Ohio, and returned to him a title ring that the 38-time tour winner had given him in the hospital in Boston. Cameron used it as inspiration during his recovery, then knew what he had to do.

I know how tough it is to win a PBA tournament and I didnt want to just accept something from him like that, he said. It was his hard work, not mine.

Put an X down in the character frame.

While the high school season started slowly for Cameron, he came on strong and raised his average 10 pins in the final fourmatches.

His 1,298 series (six games), including 244 and 257 games, led all Class B bowlers at sectionals and paced Brighton to third place. At the state tournament, he led the Section V team with a 1,288 series with high games of 215, 220 and 255.

At first I think I put too much pressure on myself, wanting to do well so badly, said Cameron, whose 95 average in the classroom rivals his performanceon the lanes. Once I just relaxed a little bit, I was bowling a lot better and I ended up bowling four amazing series the last four matches to make the composite team.

In his 19 seasons as Brightons coach, Wasserman has never met anyone with Camerons level of interest in every aspect of the game.

Bowling is his No. 1 thing, Wasserman said. Funny, but Id visit him in the hospital and there he was watching bowling on TV. What kept him going was his goal of getting back this year, and sure enough he was out there at the start.

All thanks to another hero hes never met a 30-year-old father of five sons from Rowlett, Texas, near Dallas who became his bone marrow donor.

Bryan Eddy, 30, of Rowlett, Texas and his 1 1/2-year-old son Leo. Eddy, Cameron Hurwitz's bone marrow donor, was moved to give back after his own son needed blood transfusions during 15-hour surgery to save his life after being born with a defect.(Photo: BRYAN EDDY)

Bryan Eddy, who manages a Texas Roadhouse restaurant, signed up for Be the Match while spending many hours walking the halls of Texas Childrens Hospital in Houston where his son, Leo, was born prematurely with a birth defect.

Thankful for the blood donations that helped save his son who needed surgery and spent three months in the hospital Leo is a healthy 1-year-old today Eddy was moved to give back. In just one month, he was contacted and told he was an O-negative match for a young boy in Rochester, N.Y.

Doctors extracted Eddys liquid marrow from both sides of his back near his pelvic bone under anesthesia and it was shipped to Boston.

After one year, patient and donor have the option of learning each others identity. Eddy and the Hurwitzes have spokenby phone and plan to meet this summer.

Hes a great kid and Im so happy it all worked out and he came through. Its pretty exciting, Eddy said. I was just doing anything I could to help someone else. It was my first time under anesthesia so I was nervous about that but it was really no worries on my end. I did the procedure on Monday, I recovered on a Tuesday and I was back to work on Wednesday. Cameron did all the work, my deal was easy-peasy.

After learning of Camerons bowling prowess, Eddy, a big sports fan, has watched his YouTube videos.

Hes good and I can tell what a great family they are, he said. So much love. To talk to Caryn and hear the joy in her voice and Cameron, to know I helped him out, there are no words to describe that.

As there are no words to properly say Thank you for the gift of life.

He sounds really cool, Cameronsaid. I cant wait to meet him.

Caryn Hurwitz, who put her home hairdressing business on hold to take care of her son, never hesitates these days to encourage people to give blood or join the bone marrow registry.

Were so grateful, she said. Every days a blessing. I feel its my calling now to get people to sign up and to be an advocate. Something like this, it changes you. What you set out to do and what youre here for now.

Soft-spoken and modest, Cameron isnt comfortable telling his story, but he knows it might help other kids battling an illness or facing some other challenge.

Inside his personal pro shop at his dads business, Magnum Shielding on Monroe Avenue, there is a ball drill press twice his size that was a gift from the Make-A-Wish Foundation. A poster from his hospital stay hangs on a wall: Happy Transplant Day Cameron, AKA Lil Duke.

At first it was kind of interesting to tell people but right now I dont like thinking about the past, he said. But Id tell them (other children who are ill) to stay strong and see the bright side of things and eventually everything will just be a memory.

As usual, the kid hit the pocket.

LROTH@Gannett.com

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Brighton bowler Cameron Hurwitz rolls on after bone marrow transplant - Rochester Democrat and Chronicle

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'Cradle of life' stem cells taken from skin samples were developed into three-dimensional brain-like organisms capable of exchanging signals between each other in a network.

The petri dish cells behave in a similar way to the brain cells which produce messenger dopamine from neurons - and scientists hope they will be able to use them to come up with a cure for Parkinson's.

Dopamine maintains smooth body movements, but when the neurons die off, tremors, rigid muscles and other Parkinson's disease symptoms begin to take over.

The new developments mean scientists can now use the cells to test what environmental factors like pollutants have on the onset of the disease and potentially find a cure.

Lead author Professor Jens Schwamborn said: "Our cell cultures open new doors to brain research.

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"We can now use them to study the causes of Parkinson's disease and how it could possibly be effectively treated."

Our cell cultures open new doors to brain research

Professor Jens Schwamborn

The stem cells can be transformed into any cell type of the human body but cannot produce a complete organism.

PHD student Anna Monzel developed a procedure to convert the stem cells into brain cells as part of her doctoral thesis.

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Getty Images

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Tremor - One of the most noticeable signs of Parkinson's is a tremor that often starts in the hands or fingers when they are relaxed

She said: "I had to develop a special, precisely defined cocktail of growth factors and a certain treatment method for the stem cells, so that they would differentiate in the desired direction."

Prof Schwamborn from the Luxembourg Centre for Systems Biomedicine at Luxembourg University said: "Our subsequent examination of these artificial tissue samples revealed that various cell types characteristic of the midbrain had developed."

"The cells can transmit and process signals.

"We were even able to detect dopaminergic cells - just like in the midbrain."

The scientists say their petri dish study can also reduce the amount of animal testing in brain research.

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Because cell cultures in the petri dishes are of human origin in some aspects they resemble human brains more than the brains of lab animals such as rats or mice.

Professor Schwamborn added: "There are also attractive economic opportunities in our approach.

"The production of tissue cultures is highly elaborate.

"In the scope of our spin-off Braingineering Technologies Sarl, we will be developing technologies by which we can provide the cultures for a fee to other labs or the pharmaceutical industry for their research."

The study was published in the Stem Cell Reports journal.

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Scientists one step closer to turning stem cells into BRAIN | Health ... - Express.co.uk

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UPDATED: Fri., April 14, 2017, 10:04 p.m.

Elson S. Floyd College of Medicine assistant research professor Jason Gerstner leads the research team studying fruit flies brains and sleep patterns. (Dan Pelle / The Spokesman-Review)

A research team led by a Washington State University biochemist could help scientists shed light on why we need to sleep, and why some people have an easier time resting than others.

Jason Gerstner, a research assistant professor at WSUs Elson S. Floyd College of Medicine, found that mutations in a sleep gene in the brain can cause humans, mice and fruit flies to have less restful sleep.

The results of the study were published in a peer-reviewed article in the journal Science Advances earlier this month.

It might sound odd, but scientists still arent sure why sleep is necessary. One theory is that sleep helps with memory formation and the brains growth and change: what scientists call neuroplasticity. Other theories maintain that sleep is restorative for the body and that it lowers metabolism, helping to conserve energy.

We still dont fully understand what biological function sleep is serving, Gerstner said. One of the ways we can get at answering that question is through examining neurobiological pathways.

Much of Gerstners research has focused on a particular gene, FABP7, thats been linked to sleep function. In previous research, Gerstner saw the genes expression cycles naturally during the day in mice, mirroring sleep-wake cycles.

For this study, Gerstners team looked at a sleep study of Japanese men, some of whom had a naturally occurring mutation in their FABP7 gene. Men with the mutation slept about as long as men without it, but their sleep was more fitful, with more bouts of time spent awake during the night.

Men with the mutation also reported more symptoms indicating clinical depression on an assessment, though neither group scored high enough to meet the criteria for depression. Gerstner said that suggests either the gene mutation itself or sleep disturbance might be linked to depression in some way.

There were no significant differences in health, age or sleepiness between the two groups of men.

The study showed similar restlessness in rats that had their FABP7 genes knocked out and in genetically engineered fruit flies with the same gene mutation. Because the mutation works the same way across species, its a promising finding for future research, and even for treatment of sleep disorders.

The FABP7 mutation causes the gene to create a different protein sequence. That affects which other proteins in the brain the sequences bind to, which in turn can influence a broad range of functions, like gene expression, inflammation and other brain functions.

The researchers also found the specific part of the brain, a star-shaped cell called an astrocyte, where FABP7 plays a role in sleep.

Previously, those cells were thought to be support cells for neurons, Gerstner said. Now, scientists are learning theyre important in their own right.

This is some of the earliest evidence that astrocytes really play a role in sleep, said Isaac Perron, a doctoral student in neurobiology at the University of Pennsylvania who worked with mice in the experiment.

Perrons interest is in sleep and nutrition. Because the proteins coded by FABP7 bind with fatty acids like omega-3s, he thinks the gene might be a link in showing how the fatty acids we eat can influence brain functions, including sleep.

Jerry Yin, a professor of genetics at the University of Wisconsin-Madison, who worked on the fruit fly portion of the research, said finding a common pathway like FABP7 helps people looking at medications or gene therapies target their treatments.

Knowing FABP7 works in astrocytes helps researchers tailor their focus, since those cells are where youre likely to have an effect manipulating this gene, Yin said.

Testing a therapy or medication is also easier because the FABP7 impact on sleep works in fruit flies and mice, both of which are commonly used in research.

Since weve narrowed down particular protein expressed within astrocytes, it underscores the importance of these cells in regulating complex behavior across species, Gerstner said.

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WSU sleep researchers discover why some people may toss and turn more than others - The Spokesman-Review

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Men's Health

I Tried Sound Wave Therapy For Stronger Erections. Here's What Happened Men's Health He grinned the grin of a 60-plus-year-old doctor jacked up on growth hormone and testosterone. I think you're gonna be pretty happy. Let's get that numbing cream on, shall we? I grimaced, half-expecting him to snatch the syringe from my clutch and ...

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I Tried Sound Wave Therapy For Stronger Erections. Here's What Happened - Men's Health

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Vitamins are defined as organic substances occurring in many foods in small amounts that are necessary for the normal metabolic functioning of the body. Vitamin D is one of the fat-soluble vitamins. Our bodies can't manufacture vitamins but can manufacture hormones, and some experts feel that vitamin D should be classified as a hormone rather than a vitamin because our bodies manufacture it when exposed to the sun.

"Current Medical Diagnosis and Treatment 2016" notes that vitamin D deficiency "is increasing throughout the world as a result of diminished exposure to sunlight caused by urbanization, automobile and public transportation, modest clothing and sunscreen use."

Defining vitamin D deficiency can be confusing due to two ways of measuring level: nmol/liter and ng/ml (e.g. 112 nmol/liter is the same as 50 ng/ml). The latter is the way levels are usually reported and is what will be used in today's column. Significant vitamin D deficiency is defined as a level less than 20 ng/ml and this occurs in 29 percent of postmenopausal American women and 25 percent of American men older than 65. Severe deficiency is defined as a level less than 10 ng/ml and is present in 3.5 percent of Americans.

Almost all cells, organs and tissues in our bodies have vitamin D receptors, and vitamin D can also turn on hundreds of genes. Over the years, vitamin D supplementation has been touted as a panacea for all sorts of health problems, but according to Dr. Michael Greger's website nutritionfacts.org, better studies done in the last few years have discounted many of these claims. Here's what the current science tells us about vitamin D deficiency:

Vitamin D promotes calcium absorption by the intestines, and also stimulates the activity of bone-forming cells called osteoblasts. Deficiency can cause osteoporosis and osteomalacia, which like osteoporosis causes brittle bones and fractures, but is not exactly the same as osteoporosis. In children with developing bones, osteomalacia is called rickets, which can result in permanent skeletal deformities.

There are vitamin D receptors in our muscles and nervous systems including our brains, but as we age the number of receptors decreases. Elderly people with low vitamin D levels are more apt to suffer falls due to muscle weakness and balance problems.

Vitamin D boosts our immune system, and people with low D levels have an increased incidence of respiratory infections.

Low vitamin D levels are associated with increased all-cause mortality (i.e. you live longer if you maintain normal vitamin D levels).

Vitamin D helps fight inflammation. Asthma, ulcerative colitis and Crohn's disease all inflammatory diseases improve and in some cases even go into remission once D levels have normalized.

According to Dr. Joel Fuhrman, author of "Eat to Live" and other books, "Vitamin D regulates several genes and cellular processes related to cancer progression." People with low levels of D are more apt to get several cancers including breast and colon, and once they get cancer it is more likely to progress.

What are normal levels? Greger points out that the cradle of civilization was in equatorial Africa, "when people were running around outside naked." Vitamin D levels in African tribes living traditional lifestyles are around 50. Breast milk lacks vitamin D, and therefore breast-fed babies are given D supplements, which doesn't make sense from an evolutionary point of view. But if a breast-feeding mother's D level is 50 or greater, her breast milk does contain vitamin D. So while some guidelines say we should shoot for levels of D greater than 30, most of the science points to levels of 50 or more as ideal.

How much D should people take to achieve levels of 50 or above? For most people, 2,000 units a day achieves optimal D levels, with some caveats:

Vitamin D is stored in fat, so obese people need to take 4,000 units a day a day to achieve optimal levels.

Absorption is hampered in the elderly, so the American Geriatrics Society recommends 4,000 units in people 65 and older.

The type of vitamin D you should take is D3, which is what your body makes when exposed to sunlight; versus D2 present in yeast and mushrooms, which isn't as effective.

D is absorbed better if taken with a meal that contains some fat, such as nuts and seeds.

The practice of taking very high doses (e.g. 50,000 units) intermittently is now frowned upon, because the very high levels that result can cause problems.

How about just getting sun exposure rather than taking a supplement? The problem is that sun ages your skin and causes skin cancer. When outside you should cover up and apply sunscreen to exposed areas of your skin such as your face, but this interferes with vitamin D production. Tanning booths have the same problems as sun exposure, and aren't very effective in vitamin D production anyway.

Should everyone have their vitamin D levels tested? Most guidelines don't recommend this because:

Almost all Americans are lower than optimal in vitamin D.

Most insurance companies and Medicare won't cover the test when coded as a screen.

The test for vitamin D is done on a blood sample, and is not a very accurate test in that a lot of variation can occur between labs and even on the same sample tested repeatedly in the same lab.

Vitamin D is inexpensive and has no side effects except in very high doses, such as 10,000 units a day, which can result in dangerously high blood levels.

Dr. Feinsinger, who retired from Glenwood Medical Associates after 42 years as a family physician, now has a nonprofit Center For Prevention and Treatment of Disease Through Nutrition. He is available for free consultations about heart attack prevention and any other medical concerns. Call 970-379-5718 for an appointment. For questions about his columns, email him at gfeinsinger@comcast.net.

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Doctor's Tip: The low-down on vitamin D - Glenwood Springs Post Independent

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Once a pioneer, Johns Hopkins Hospital is returning to the field of transgender healthcare. But the controversial beliefs of Dr. Paul McHugh still pose complications.

Paula Neira still lives by a motto she learned in the navy: semper porro, ever forward.

Thats why Neira, the clinical director of the new Johns Hopkins Center for Transgender Health and a transgender woman herself, isnt letting herself get bogged down by the institutions rocky past around transgender issues.

Its real easy to change course on a little patrol boat; its real difficult to change course on a dime on an aircraft carrier, she told The Daily Beast. These institutions are big institutions. But when you have the commitment from the leadership on down to change course, youll change course.

Once the first medical institution in the U.S. to offer sex reassignment surgery in the 1960s, it has taken nearly forty years for Johns Hopkins Medicine to return to the field of transgender health care after the original clinic was shut down in 1979 at the urging of Dr. Paul McHugh, then chair of the psychiatry department.

McHugh, now 85, has remained vocally opposed to transgender medical care ever since. And his continuing affiliation with the university has left some in the LGBT community concerned that the new centerscheduled to open in the summer of 2017, offering hormone therapy, surgeries, and other services to transgender patientswont do enough to repair Hopkins reputation.

For instance, after the Washington Post published a front-page feature last week focusing largely on McHughs reaction to the opening of the Center for Transgender Health, Human Rights Campaign national press secretary and transgender advocate Sarah McBride responded with an opinion piece saying that Hopkins has a long way to go before transgender people feel safe.

While the opening of the clinic is important, that alone cannot heal the wounds inflicted by Hopkins against transgender people nor alleviate the ongoing harm caused by the continued invocation of its credibility to support Mr. McHughs essays attacking LGBTQ people, McBride concluded. The only path toward inclusive care requires Hopkins to clearly speak out.

McHughs name, as The Daily Beast has previously reported, has become a staple in anti-LGBT circles. His 2014 Wall Street Journal op-ed Transgender Surgery Isnt the Solution, in particular, has been widely-cited. But his views on transgender health care are dramatically out of step with major medical associations, which support and affirm transgender medical care.

According to the American Medical Association, for example, there is an established body of medical research that shows the effectiveness and medical necessity of mental health care, hormone therapy and sex reassignment surgery as forms of therapeutic treatment for many transgender people.

And as the disjuncture between McHughs views and medical consensus has become more pronounced, Johns Hopkins Medicine has taken public steps to reassure the LGBT community that no single individual represents the institution as a whole.

Last October, two months after McHugh co-authored a paper questioning the concepts of sexual orientation and gender identity, Johns Hopkins Medicine leadership published a Dear colleagues letter stating that the institutions commitment to the LGBT community is strong and unambiguous, acknowledging that some have questioned our position because of the varied individual opinions expressed publicly by members of the Johns Hopkins Medicine community.

And in a new statement to The Daily Beast issued in response to questions about concerns like McBrides that exist in the transgender community, a Johns Hopkins Medicine spokesperson stated: Johns Hopkins Medicine has and is taking steps toward becoming an employer and provider of choice for all, including transgender individuals. And statements or actions to the contrary by current or former affiliates of Johns Hopkins do not reflect our institutions current views. We are committed to being a caring, inclusive place for all patients, families and employees.

Despite the October 2016 statement, the Human Rights Campaign this March deducted 25 points from Johns Hopkins Hospitals Healthcare Equality Index score, attributing it to Johns Hopkins Medicines failure to address HRCs concerns regarding deeply disturbing anti-LGBTQ misinformation written by McHugh.

Neirawho transitioned after leaving the navy, going on to become a registered nurse and an attorney advocating for the repeal of Dont Ask, Dont Tellfully realizes that McHughs presence will have some impact on the transgender communitys perception of the new center.

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Were aware that theres going to be skepticism in some quarters because of the history, because of McHughs writings, she told The Daily Beast. But his writings dont reflect the institutions values and where were going.

Neira believes that transgender people are smart consumers who tend to be much more informed about their care than averageoften out of necessity, given how frequently they have to educate their own physiciansand she hopes that the new center will be judged by its actions rather than the words of one doctor.

The folks in the community will make up their mind about what we do, she said. And as the clinical program director for the center, I wouldnt be in this role if [Hopkins] wasnt committed to doing this right.

The World Professional Association of Transgender Health, the leading organization for transgender health care professionals, is cautiously optimistic about the new Hopkins clinic. In written statements to The Daily Beast, treasurer Dr. Walter Bouman said that WPATH welcomes new transgender healthcare services to increase access of care for trans people and immediate past president Dr. Jamison Green said that it was a positive move.

We will have to see what policies the clinic uses, and what principles inform their procedures, added Green. I think it is a positive sign, though, that Johns Hopkins is willing to add to the knowledge base concerning genderand I expect the new crop of clinicians will have benefited from all the good work that has been done in the field since their original clinic was closed nearly 40 years ago. (Neira indicated to The Daily Beast that the new center would indeed use WPATHs Standards of Care.)

In a follow-up interview with The Daily Beast, Green disagreed with the idea that Hopkins Medicine should specifically call out McHughs writings: If they give him that much attention, that is simply going to elevate his profile.

Green called it a big deal that a health care leader like Hopkins would open a transgender health center as it reinforces the idea that this is meaningful.

As for McHugh himself, he reiterated in a phone interview with The Daily Beast that he disagrees with the idea that his writings pose any threat to transgender people.

I certainly am not wounding anybody, he said. I am saying that the treatments that are being offered do not help them.

McHugh has known for months that Hopkins would re-enter the field of transgender medicine. As the Washington Post reported in last weeks feature, McHugh received a visit from the head of plastic and reconstructive surgery last fall, who informed him that Johns Hopkins Hospital would once again start offering sex reassignment surgery. The Post reported, paraphrasing McHugh, that he bears no animus for transgender health providers at Hopkins.

He told The Daily Beast that although he has no hard feelings for his colleagues at Hopkins who made the call, he has voiced his disagreement.

When asked by The Daily Beast if he thought it was a mistake for Johns Hopkins Medicine to open the new transgender health center, he said, Yes and I think they will regret it and Ive told them so.

Asked what they said back to him, McHugh laughed gently.

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Can Trans People Trust Johns Hopkinss New Clinic? - Daily Beast

Recommendation and review posted by Bethany Smith

Many children and adolescents are "trying out" identifying as transgender because they think it will make them "different," an Australian psychiatristwho runs a gender clinic in Brisbane told the tabloidThe Courier-Mail. He said many more teens and young adults come into his clinic seeking transgender treatments than are actually suffering with long-term gender dysphoria.

"One said to me, 'Dr Steve ... I want to be transgender, it's the new black'," Dr. Stephen Stathis, a pediatric psychiatrist and medical director of child and youth mental health services at Children's Health Queensland Hospital and Health Service, toldThe Courier-Mail. He said he had seen a lot of adolescents "trying out being transgender" to stand out.

Stathis estimated that his gender service would see about 180 children with gender issues, but argued that only a minority would be diagnosed with gender dysphoria. By the time these kids reach puberty, most will identify as their birth gender, he predicted.

Rather than a cultural fad like transgenderism among teens seems to have become, gender dysphoria is a strong, persistent feeling of identification with the opposite gender and discomfort with one's own assigned gender.

One of the trends Stathis has seen is truly heartbreaking. Many young girls have come into his clinic after having been sexually abused, and wanted to change their gender to avoid more abuse.

"The girls say, 'If only I had been a male I wouldn't have been abused'," Stathis said. Situations like this are tragic, but not a justification for long-term surgeries and hormone treatments which may end up damaging girls who have already been abused. Rather than a solution, it seems this would only worsen their trauma.

The Courier-Mail reported that Stathis "has also seen transgender children so desperate to start puberty blockers then progress to irreversible hormone treatment they harm themselves." Warning: this description will be very disturbing.

"I've seen genital mutilation, some who try to cut off their penis," the psychiatrist said. "The thought of touching their genitals is so abhorrent they don't wash them and get infections."

At the end of last year, Stathis reported there was a two-year waiting list of 100 children wanting to be assessed at the hospital. With state funding, the wait is now down to three or four months, and the service has seen more than 60 patients since December. While it is a good thing more adolescents will actually be checked out by professionals who acknowledge that not all kids who identify as transgender are truly suffering from gender dysphoria, some would argue that even the minority who do are ill-served by suggestions they should irreversibly alter their bodies to match their inner identities.

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Kids 'Trying Out' Transgenderism Say 'It's the New Black' - PJ Media

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Ottawa Sun

Jonathan Pitre 'anxious' as he readies for his second transplant Thursday Ottawa Sun Boileau goes into surgery at the University of Minnesota Masonic Children's Hospital at 5:30 a.m. Thursday to have bone marrow drawn from her hip. Surgeons will bore two holes into her pelvis and withdraw the bone marrow, a material rich in stem cells; ... and more »

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Jonathan Pitre 'anxious' as he readies for his second transplant Thursday - Ottawa Sun

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It will be several weeks before Jonathan Pitre finds out if his second stem-cell transplant was successful. Tina Boileau / -

The perilous wait now begins for Jonathan Pitre.

Pitre, 16, was transfused with blood and marrow drawn from his mothers hip late Thursday afternoon. The stem-cell rich material holds the power to alter the course of Pitres aggressive skin disease, epidermolysis bullosa (EB), and change his life.

So far, so good, saidPitres mother, Tina Boileau.

It will be several weeks before Pitre finds out whether the transplant has worked its magic.

While waiting for that answer, theRussell teenager will have to travel the most difficult part of his medical journey: a time when his immune system is at its lowest ebb, and when he feels the full effects of high-dose chemotherapy and radiation.

His physician, Dr. Jakub Tolar, has warned that the period represents the highest risk for complications, the most common of which are infections and graft-versus-host disease (GVHD). It is a potentially life-threatening situation in which the implanted stem cells produce T-cells that attack normal cells.

In about two weeks time, doctors will start to look for signs that Boileaus stem cells have successfully established themselves in Pitres bone marrow.The presence of white blood cells is one of the earliest signs of stem-cell growth; an improvement in the condition of Pitres skin could also signal that the stem cells have started to work.

Last year, after his first stem-cell transplant, Pitre and his mother were thrilled when doctors discovered new white cells in his bloodstream. But their hopes were crushed when tests showed Pitres own stem cells had recolonized his bone marrow, and were producing the cells.

This time, Boileau said, they will wait to see more lab results before getting their hopes too high.

I think we will have that uncertainly until we know for sure through skin and bone marrow biopsies that the engraftment worked, she said.

Boileau went into surgery early Thursday morning to have blood and bone marrow drawn from her hip. She was at her sons bedside later in the afternoon to watch as the stem cells dripped through an intravenous tube connected to the right atrium of her sons heart.

If the transplant works, Boileaus stem cells will establish themselves in her sons bone marrow, grow, divide and make new blood cells equipped with the power to provide Pitre with the key protein he needs to rebuild his damaged skin.

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His stem-cell transplant complete, the wait begins for Jonathan Pitre - Ottawa Citizen

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The most complex organ in humans is the brain. Due to its complexity and, of course, for ethical reasons, it is extremely difficult to do scientific experiments on it -- ones that could help us to understand neurodegenerative diseases like Parkinson's, for example. Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have now succeeded in turning human stem cells derived from skin samples into tiny, three-dimensional, brain-like cultures that behave very similarly to cells in the human midbrain. In the researchers' petri dishes, different cell types develop, connect into a network, exchange signals and produce metabolic products typical of the active brain. "Our cell cultures open new doors to brain research," says Prof. Dr. Jens Schwamborn, in whose LCSB research group Developmental & Cellular Biology the research work was done. "We can now use them to study the causes of Parkinson's disease and how it could possibly be effectively treated." The team publishes its results today in the scientific journal Stem Cell Reports.

The human midbrain is of particular interest to Parkinson's researchers: it is the seat of the tissue structure known medically as the substantia nigra. Here, nerve cells -- specifically dopaminergic neurons -- produce the messenger dopamine. Dopamine is needed to maintain smooth body movements. If the dopaminergic neurons die off, then the person affected develops tremors and muscle rigidity, the distinctive symptoms of Parkinson's disease. For ethical reasons, researchers cannot take cells from the substantia nigra to study them. Research groups around the world are therefore working on cultivating three-dimensional structures of the midbrain in petri dishes. The LCSB team led by stem cell researcher Jens Schwamborn is one such group.

The LCSB scientists worked with so-called induced pluripotent stem cells -- stem cells that cannot produce a complete organism, but which can be transformed into all cell types of the human body. The procedures required for converting the stem cells into brain cells were developed by Anna Monzel as part of her doctoral thesis, which she is doing in Schwamborn's group. "I had to develop a special, precisely defined cocktail of growth factors and a certain treatment method for the stem cells, so that they would differentiate in the desired direction," Monzel describes her approach. To do this, she was able to draw on extensive preparatory work that had been done in Schwamborn's team the years before. The pluripotent stem cells in the petri dishes multiplied and spread out into a three-dimensional supporting structure -- producing tissue-like cell cultures.

"Our subsequent examination of these artificial tissue samples revealed that various cell types characteristic of the midbrain had developed," says Jens Schwamborn. "The cells can transmit and process signals. We were even able to detect dopaminergic cells -- just like in the midbrain." This fact makes the LCSB scientists' results of extraordinary interest to Parkinson's researchers worldwide, as Schwamborn stresses: "On our new cell cultures, we can study the mechanisms that lead to Parkinson's much better than was ever the case before. We can test what effects environmental impacts such as pollutants have on the onset of the disease, whether there are new active agents that could possibly relieve the symptoms of Parkinson's -- or whether the disease could even be cured from its very cause. We will be performing such investigations next."

The development of the brain-like tissue cultures not only opens doors to new research approaches. It can also help to reduce the amount of animal testing in brain research. The cell cultures in the petri dishes are of human origin, and in some aspects resemble human brains more than the brains of lab animals such as rats or mice do. Therefore, the structures of human brains and its modes of function can be modelled in different ways than it is possible in animals. "There are also attractive economic opportunities in our approach," Jens Schwamborn explains: "The production of tissue cultures is highly elaborate. In the scope of our spin-off Braingineering Technologies Sarl, we will be developing technologies by which we can provide the cultures for a fee to other labs or the pharmaceutical industry for their research."

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Materials provided by University of Luxembourg. Note: Content may be edited for style and length.

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Brain tissue from a petri dish: Stem cell research -- ScienceDaily - Science Daily

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April 10, 2017 06:00 ET | Source: Mesoblast Limited

NEW YORK and MELBOURNE, Australia, April 10, 2017 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO) (ASX:MSB) today announced that thePhase 3 trial ofits allogeneic mesenchymal precursor cell (MPC) product candidate MPC-150-IM in patients with moderate to advanced chronic heart failure (CHF)was successful in thepre-specified interim futility analysisof the efficacy endpoint in the trial's first 270 patients. It is expected that the trial will enroll in total approximately 600 patients. After notifying the Company of the interim analysis results, thetrials Independent Data Monitoring Committee (IDMC) additionally stated that they had no safety concerns relating to MPC-150-IM and formally recommended that the trial should continue as planned.

Dr. Emerson C. Perin,Director, Research in Cardiovascular Medicine and Medical Director, Stem Cell Center at the Texas Heart Institute, and a lead investigator on the ongoing Phase 3 trial said: "It is very pleasingto see that thislarge and rigorously conducted Phase 3 trialof Mesoblast's cell therapy was successful in the pre-specified interim futility analysis for the trial's efficacy endpoint in the first 270 patients. Advancedheart failure is a very serious and life-threatening disease, and there is an urgent need to develop a safe and effective new therapy for these patients that may halt or reverse disease progression and prevent the high associated mortality.

Mesoblast Chief Executive Silviu Itescucommented: Passing this interim futility analysis for MPC-150-IM is an important milestone for Mesoblast and our cardiovascular disease program. This validates our strategy and our prioritization of this valuable program.

This ongoing double-blinded randomized (1:1) trial is currently being conducted across multiple study sites in the United States and Canada.It is evaluating MPC-150-IM in adult patients with moderate to advanced New York Heart Association (NYHA) Class II/III chronic heart failure with left ventricular systolic dysfunction. The trials primary efficacy endpoint is a comparison of recurrent non-fatal heart failure-related major adverse cardiac events (HF-MACE) in moderate to advanced CHF patients receiving either MPC-150-IM by catheter injection into the damaged left ventricular heart muscle or sham control. A Joint Frailty Model is the statistical method that evaluates multiplenon-fatal heart failure-relatedevents per patient (such as repeated hospitalizations for decompensated heart failure) while accounting for increased likelihood of a terminal cardiac event (such as death, implantation of a mechanical heart assist device or a heart transplant) for patients with multiple non-fatal heart failure events. In line with best practice for blinded Phase 3 clinical trials, the interim analysis data are only reviewed by the IDMC. Mesoblast, the United States Food and Drug Administration (FDA), and trial investigators are blinded to grouped safety and efficacy data for the ongoing trial as well as the numerical results of this interim analysis.

About Mesoblasts MPC-150-IM Cardiovascular Program MPC-150-IM is Mesoblast's lead allogeneic, cell-based product candidate for the treatment of moderate to advanced chronic heart failure (CHF) due to left ventricular systolic dysfunction.

In Phase 2 results, a single injection of MPC-150-IM into the myocardium of patients with moderate to advanced chronic heart failure prevented any HF related hospitalizations or cardiac deaths over three years of follow-up.1 Nonclinical studies showed that intramyocardial administration of MPCs in animal models of heart failure improved cardiac function and attenuated pathological ventricular remodelling. These effects were attributable, at least in part, to MPC secretion of biomolecules that stimulate reparative processes in the failing heart including new blood vessel formation, cardiac muscle cell survival, and reduction in tissue fibrosis.

MPC-150-IM is also being studied in a Phase 2b trial in 159 patients with NYHA Class IV end-stage heart failure patients in conjunction with implantation of a left ventricular assist device (LVAD).A major objective of this trial, which is being sponsored by the United States National Institutes of Health (NIH), is to assess the ability of MPC-150-IM to help wean patients from a LVAD dependent existence for survival (so-called bridge to recovery).

Additionally, the FDA recently cleared the commencement of a 24-patient trial which is being sponsored by Bostons Childrens Hospital. This study combines Mesoblast's proprietary allogeneic MPC-150-IM product with corrective heart surgery in children under the age of 5 with hypoplastic left heart syndrome.

About Chronic Heart Failure In 2016, more than 15 million patients in the seven major global pharmaceutical markets are estimated to have been diagnosed with CHF.2 Prevalence is expected to grow 46% by 2030 in the United States alone, affecting more than 8 million Americans.3 CHF is a progressive disease and is classified in relation to the severity of the symptoms experienced by the patient. The most commonly used classification system was established by the NYHA and ranges from Class I (mild) to Class IV or end stage (severe). Approximately half of people who develop heart failure die within 5 years of diagnosis.4 Patients with late NYHA Class II or Class III CHF continue to represent a significant unmet medical need despite recent advances in new therapies. CHF causes severe economic, social, and personal costs. In the United States, it is estimated that CHF results in direct costs of $60.2 billion annually when identified as a primary diagnosis and $115 billion as part of a disease milieu.5

1.Perin EC, Borow KM, Silva GV, et al. A phase II dose-escalation study of allogeneic mesenchymal precursor cells in patients with ischemic or nonischemic heart failure. Circ Res. 2015; 117:576-84

2.GlobalData-PharmaPoint (2016): Heart Failure-Global Drug Forecast and Market Analysis to 2025

3.AHA Statistical Update Heart Disease and Stroke Statistics-(2017). Circulation. 2017;131:00-00. DOI: 10.1161/CIR.0000000000000485

4.Mozzafarian D, Benjamin EJ, Go AS, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics2016 update: a report from the American Heart Association. Circulation. 2016;133:e38-e360

5.A Re-Evaluation of the Costs of Heart Failure and its Implications for Allocation of Health Resources in the United States. Voigt J. Clinl.Cardiol. 37, 5, 312-321 (2014)

About Mesoblast Mesoblast Limited (Nasdaq:MESO) (ASX:MSB)is a global leader in developing innovative cell-based medicines. The Company has leveraged its proprietary technology platform, which is based on specialized cells known as mesenchymal lineage adult stem cells, to establish a broad portfolio of late-stage product candidates. Mesoblasts allogeneic, off-the-shelf cell product candidates target advanced stages of diseases with high, unmet medical needs including cardiovascular conditions, orthopedic disorders, immunologic and inflammatory disorders and oncologic/hematologic conditions.

Forward-Looking Statements This press release includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast's actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

Related Articles

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Successful Interim Analysis of Efficacy Endpoint in Mesoblast's Phase 3 Trial for Chronic Heart Failure - GlobeNewswire (press release)

Recommendation and review posted by sam

Inkjet printers and lasers are parts of a new wayto produce cells important to research on nerve regeneration.

Schwann cells, for example, form sheaths around axons, the tail-like parts of nerve cells that carry electrical impulses. They promote regeneration of those axonsand secrete substances that promote the health of nerve cells. But theyre hard to come by in useful numbers.

This technology could lead to a better way to differentiate stem cells.

So researchers have been taking readily available mesenchymal stem cells (also called bone marrow stromal stem cells that can form bone, cartilage, and fat cells) and using a chemical process to differentiate them into Schwann cells. But its an arduous and expensive process.

Researchers at Iowa State University have developed a nanotechnology that uses inkjet printers to print multi-layer graphene circuits and also uses lasers to treat and improve the surface structure and conductivity of those circuits.

It turns out mesenchymal stem cells adhere and grow well on the treated circuits raised, rough, and 3D nanostructures. Add small doses of electricity100 millivolts for 10 minutes per day over 15 daysand the stem cells become Schwann-like cells.

This technology could lead to a better way to differentiate stem cells, says co-first author Metin Uz, a postdoctoral research associate in chemical and biological engineering. There is huge potential here.

The electrical stimulation is very effective, differentiating 85 percent of the stem cells into Schwann-like cells compared to 75 percent by the standard chemical process, according to the paper. The electrically differentiated cells also produced 80 nanograms per milliliter of nerve growth factor compared to 55 nanograms per milliliter for the chemically treated cells.

The researchers report the results could lead to changes in how nerve injuries are treated inside the body.

These results help pave the way for in vivo peripheral nerve regeneration where the flexible graphene electrodes could conform to the injury site and provide intimate electrical stimulation for nerve cell regrowth, the researchers write in a summary of their findings.

The paper reports several advantages to using electrical stimulation to differentiate stem cells into Schwann-like cells:

A key to making it all work is a graphene inkjet printing process that takes advantages of graphenes wonder-material propertiesits a great conductor of electricity and heat, its strong, stable, and biocompatibleto produce low-cost, flexible, and even wearable electronics.

But there was a problem: once graphene electronic circuits were printed, they had to be treated to improve electrical conductivity. That usually meant high temperatures or chemicals. Either could damage flexible printing surfaces including plastic films or paper.

The research group of lead author Jonathan Claussen, assistant professor of mechanical engineering and an associate of the US Department of Energys Ames Laboratory, solved the problem by developing computer-controlled laser technology that selectively irradiates inkjet-printed graphene oxide.

The treatment removes ink binders and reduces graphene oxide to graphenephysically stitching together millions of tiny graphene flakes. The process makes electrical conductivity more than a thousand times better.

That led to experimental attempts to grow stem cells on printed graphene and then to electrical stimulation experiments.

We knew this would be a really good platform for electrical stimulation, says Suprem Das, a postdoctoral research associate in mechanical engineering and an associate of the Ames Laboratory. But we didnt know it would differentiate these cells.

But now that it has, the researchers say there are new possibilities to think about. The technology, for example, could one day be used to create dissolvable or absorbable nerve regeneration materials that could be surgically placed in a persons body and wouldnt require a second surgery to remove.

The findings appear in Advanced Healthcare Materials. Funding came from the Roy J. Carver Charitable Trust, the US Army Medical Research and Materiel Command, and Iowa State.

Source: Iowa State University

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How inkjet printers help transform stem cells - Futurity: Research News

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University of Minnesota researcher Perry Hackett, calls his breakthrough in using DNA to fight cancer one of the grandest Minnesota fishing stories ever.

Hackett, a professor of cell biology and genetics at the University, was given the Impact Award last month for inventing the Sleeping Beauty Transposon system a basis for many cancer-fighting immunotherapies.

Though Hacketts scientific journey began nearly 40 years ago when he was tasked with genetically engineering larger fish, his more recent work can reprogram a persons immune system to fight cancer by introducing a gene into a cell that will recognize foreign cells in the body.

Your immune system has memory, and it can target specific things that are bad, he said. It does so by targeting virus-infected cells and things like that.

Transposons are DNA that are not uniform throughout an organism a concept easily seen in Indian corn, where the kernels are multicolored because a DNA element is hopping around the corn genome.

Its named Sleeping Beauty because it was a gene that was active 13 million years ago but went extinct, Hackett said.

Because this system does not use viruses like other cancer treatments, Hackett said he and his team of three other University faculty members were awarded a grant to research using the system for human gene therapy.

The problem with viruses is theyre expensive to make, they take a long time to get and theyre very costly to purify, he said.

But the Sleeping Beauty Transposon is simple enough for an undergraduate student to make. Thats how trivial this technology is, he said.

The transposons history starts when Hackett accepted a job at the University in 1980 to study retroviruses. He said there were few restrictions on researchers and what they could do in the lab.

He and his colleagues were making mutations in cancer viruses and were not paid much attention.

A couple of my friends came to me and said, You know how to genetically engineer stuff. We want to make big fish, he said, adding that the governor at the time, Rudy Perpich, had asked someone from the medical school how it could help the fishing industry.

Hackett received money from the state and other organizations and successfully created faster-growing fish, but he said many environmentalists at the time were concerned about modified fish being in nature.

Though fish in Minnesota years ago were naturally larger and the fish population worldwide is decreasing rapidly, Hackett said the engineered fish never made it out into the wild.

All the lakes here in Minnesota are feeling pressure, he said. I would say that there now is a global fisheries crisis due to people called environmentalists and people called conservationists. The result is that the natural animal population cant keep up.

While Hackett and his teams engineered fish project came to a halt, he said they made the procedure used on the fish more efficient and eventually came up with a new transposon system.

In the early 2000s, the team merged with the Genetic Cell Biology and Development Department, which was new at the time, and started investing in transposons and gene therapy.

He said viruses have been used in the past to improve the immune system, but a few years ago immunotherapy became the focus.

Fundamentally, its a fishing story, Hackett said of creating the transposon system. "It is one of the grandest Minnesota fishing stories ever. You start to find a way to improve the lives of fishermen and you wind up with a cutting-edge tool to treat cancer.

Dan Voytas, a genetics, cell biology and development professor and the director of the Center for Genome Engineering, said he took a job at the University in 2008 partly because of Hacketts work in genetics.

Voytas said he first met Hackett shortly after the transposon discovery was made.

Part of the motivation for the move was certainly my excitement about working with professors at the University of Minnesota who are interested in editing [and] modifying DNA in cells, he said.

Voytas sees the Sleeping Beauty Transposon System as Hacketts greatest contribution to the University.

It has many applications, he said. Its been helpful in understanding how cancer progresses. Its been important to correct genetic diseases that people inherit. More recently its been important in turning our immune systems against cancer.

Voytas said the recent immune system discovery was commercially licensed in the last year and a half. Since Hacketts discovery, he said there have been other developments that allow DNA to be more precisely edited.

The Center for Genome Engineering implements other peoples systems into editing human, animal and plant genes, Voytas said.

He added that in the future, therapies based on Hacketts transposon system could eliminate or correct the symptoms of inherited diseases.

Its the therapeutic outcomes of that technology that people will appreciate and recognize, he said.

Allen Levine, the Universitys interim vice president for research and a member of the committee that awarded Hackett, said he was given the award in March because of his discovery and use of the Sleeping Beauty Transposon system.

Ive heard a lot about [Hackett] over the years, Levine said. The work that he has done has had a major impact in terms of cancer therapies.

Levine said most cancer therapies, which are relatively new, look to change the immune system to attack only cancer cells. He said 80 percent of people who use this technology have complete recovery or remission of cancer.

The University will keep on working in these arenas, he said. We want to reward that innovative thinking. I always say that genius is the recognition of the accident."

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UMN research reprograms immune system to fight cancer - Minnesota Daily

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Q. Im in doubt regarding myelodysplasia is it multipotent or pluripotent?

A. Thats a great question because it lets us talk about hematopathology (yay!) and also stem cells (which can be confusing unless someone explains some simple stuff).

What is a stem cell? First, lets talk about stem cells. The thing that makes a stem cell a stem cell, at least in my mind, is the ability to self-renew. This means that the stem cell can either divide into two daughter cells which will mature into grown up cells, or (and more commonly) it can give rise to two cells: one that will become a mature cell, and another which retains the capacity to divide again. Its called asymmetric division: instead of giving rise to two of the same cells, you get one regular cell and another stem cell (which can continue this cycle of replication for a long long time).

(Virtually) limitless replication Most cells have a limited number of times that they can divide. This is because the telomeres (little protective DNA sequences) on the end of the chromosomes get a little shorter every time the DNA replicates and eventually they are so short that they cant protect the DNA and the cell is unable to divide. Stem cells and cancer cells have an enzyme called telomerase that replenishes the telomeres, keeping them nice and long so the cell can keep on dividing. Stem cells do eventually die so technically, there are a limited number of cell divisionsbut its a really, really big number. Cancer cells, on the other hand, are often totally immortal they can just keep on dividing and dividing.

Totipotent Another cool thing about stem cells is that they can give rise to many different kinds of cells. Heres where things can get murky. There are stem cells in an embryo which are able to give rise to any of the cell types in the body: hepatocytes, epithelial cells, neurons, cardiac muscle cellseverything. This makes sense: if youre going to grow into a human, you have to have cells that give rise to all the necessary cell types. These stem cells are called totipotent or pluripotent stem cells. Theres a slight difference between the two words: totipotent means that the stem cell can give rise to any and all human tissue cells and it can even give rise to an entire functional human. The only totipotent cells in human development are the fertilized egg and the cells in the next few cell divisions.

Pluripotent After those few cell divisions, the cells become pluripotent. Pluripotent cells are similar to totipotent cells in that they can give rise to any and all human tissue cells. Theyre different, though, because they are not capable of giving rise to an entire organism. On day four of development, the tiny little embryo forms two layers: one that will become the placenta and the other that will become the baby. The cells that will become the baby can give rise to any human tissue type (obviously) but those cells alone cant give rise to the entire organism (because you cant form the baby without the placenta). Slight difference but enough to make a separate term.

Multipotent Another term you should know is multipotent. Multipotent stem cells cannot give rise to any old cell in the body they are restricted to a limited range of cell types. For example, there are multipotent stem cells in the bone marrow that can give rise to red cells, white cells and platelets. They cant give rise to hepatocytes, or any other cell type, though so they are not totipotent or pluripotent.

There are lots of multipotent stem cells in the adult human body. They reside in the bone marrow, skin, muscle, GI tract, endothelium, and mesenchymal tissues. This means that there is a nice source for replacing cells that have died or been sloughed away.

What about myelodsyplasia? So back to your question. Myelodysplasia is a hematopoietic disorder in which cells in the bone marrow grow funny (dysplasia) they might be binucleate, or not have the normal number of granules, or whatever. In addition, some cases have an increase in blasts in the bone marrow but not over 20%, or youd call it an acute leukemia. Some cases transform, eventually, into an acute myeloid leukemia; others just stay the way they are and dont become nasty.

Check out the image above, from a case of myelodysplasia. There is a bizarre, multinucleated erythroblast at 11 oclock (this is called dyserythropoiesis, or disordered red cell growth). There are also two messed-up neutrophils (dysgranulopoiesis) at 4 oclock and 10 oclock the one at 4 oclock has only two nuclear lobes, and both are hypogranular (not enough specific granulation). Theres also an increase in blasts, if this field is representative: theres one in the middle and (probably) one at 5 oclock.

This disorder (actually, its a group of disorders) involves stem cells in the bone marrow. Sometimes only one cell line is involved (red cells, say); other times all three cell lines are involved (red cells, white cells and platelets). Either way, the disorder involves a stem cell, and since the stem cells in the bone marrow are multipotent, it would be correct to say that myelodysplasia is a disorder of multipotent stem cells in the bone marrow. Its kind of redundant, though, because as far as we know, there arent any other kind of stem cells in the bone marrow! But at least you know the answer to your question now.

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Multipotent vs. pluripotent stem cells - Pathology Student

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RANCHO CORDOVA, Calif., April 11, 2017 (GLOBE NEWSWIRE) -- Cesca Therapeutics Inc. (KOOL), a market leader in automated cell processing and point-of-care, autologous cell-based therapies, today announced that Dr. Xiaochun (Chris) Xu, Chairman and Interim Chief Executive Officer and Chairman of Boyalife Group, will present an overview of the Companys cardiovascular clinical research program at the 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair, being held April 10-12, 2017 at the Hope Hotel in Shanghai, China.

Details of the presentation are as follows:

Despite recent therapeutic and surgical advances, the effects of peripheral arterial disease, including heart attack and critical limb ischemia (CLI), remain among the worlds leading causes of morbidity and mortality and represent a rapidly escalating public health crisis, noted Dr. Xu. I look forward to presenting a review of our latest findings, including key feasibility study results and an overview of our Phase 3 Critical Limb Ischemia Rapid Stemcell Treatment (CLIRST) trial, which we believe highlight the potential of Cesca Therapeutics proprietary AutoXpress point-of-care platform to deliver autologous cell-based therapies that may represent a new paradigm in patient treatment going forward.

About the Symposium of Translational Medicine in Stem Cell Myocardial Repair

The 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair brings together more than 650 of the worlds cardiac disease thought leaders to discuss the potential of translational and regenerative medicine in treating myocardial infarction (MI) and cardiac failure. The symposium is co-sponsored by the Shanghai Society for Cell Biology, the Institute of Health Sciences, the Shanghai Cardiovascular Disease Institute, the Guangzhou Institutes of Biomedicine and Health, and the Key Laboratory of Stem Cell Biology, Shanghai.

About Cesca Therapeutics Inc.

Cesca is engaged in the research, development, and commercialization of cellular therapies and delivery systems for use in regenerative medicine. The Company is a leader in the development and manufacture of automated blood and bone marrow processing systems that enable the separation, processing and preservation of cell and tissue therapeutics. Cesca is an affiliate of the Boyalife Group (http://www.boyalifegroup.com), a China-based industrial-research alliance among top research institutes for stem cell and regenerative medicine.

Forward-Looking Statement

The statements contained herein may include statements of future expectations and other forward-looking statements that are based on managements current views and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. A more complete description of risks that could cause actual events to differ from the outcomes predicted by Cesca Therapeutics' forward-looking statements is set forth under the caption "Risk Factors" in Cesca Therapeutics annual report on Form 10-K and other reports it files with the Securities and Exchange Commission from time to time, and you should consider each of those factors when evaluating the forward-looking statements.

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CESCA Therapeutics to Present at the 2017 International Symposium of Translational Medicine in Stem Cell ... - Yahoo Finance

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