A Potential New Therapeutic Option for Sickle Cell Disease and b-Thalassemia – P&T Community

WASHINGTON, Oct. 22, 2019 /PRNewswire/ -- An article published in Experimental Biology and Medicine (Volume 244, Issue 14, October 2019) (https://journals.sagepub.com/doi/pdf/10.1177/1535370219872995) reports a possible future treatment option for patients with sickle cell disease and -thalassemia. The study led by Dr. Li Liu in the Department of Biological Sciences at the University of Texas at Dallas in Richardson, Texas (USA), reports that -aminolevulinate (ALA), a heme precursor, can activate fetal -globin expression in erythroid cell systems.

Sickle cell disease (SCD) and -thalassemia are common forms of inherited blood diseases, termed hemoglobinopathies. These disorders negatively impact the quality of life and survival for millions of individuals throughout the world.These diseases are caused by mutations in the adult -globin gene that ultimately result in the production of abnormal hemoglobins. Hemoglobin is the major protein inside red blood cells and delivers oxygen to cells throughout the body.

Prior studies have demonstrated that increased levels of the fetal -globin gene product can lessen the severity in SCD and -thalassemia patients. Hydroxyurea, the first FDA approved therapeutic for SCD, works in part by increasing fetal -globin.Nonetheless, some patients do not respond to treatment with Hydroxyurea. Thus, there is an urgent need to identify new strategies that will increase -globin levels in patients suffering from SCD and -thalassemia.

In the current study, Dr. Liu and colleagues investigated the effects of ALA on -globin expression.Previous studies have shown that exogenous ALA enhances heme synthesis, globin gene expression and hemoglobin production.However, the mechanisms leading to the effects of ALA on -globin expression have not been investigated.This study reports that ALA preferentially activates -globin transcription and translation, thereby inducing fetal hemoglobin synthesis.Mechanistic studies reveal that heme biosynthesis and reactive oxygen species mediate the ability of ALA to induce -globin expression. Dr. Liu said, "These results support future studies to explore the potential of stimulating intracellular heme biosynthesis by ALA or similar compounds as a novel therapeutic strategy for treating SCD and beta-thalassemia."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology & Medicine, said, "Researchers in the sickle cell field are currently pursuing many clinical trials that would expand the FDA approved SCD therapeutic choices beyond Hydroxyurea,and the more recently approved Endari. Liu et al have provided in vitro evidence that ALA, through induction of heme biosynthesis, should be considered as a possible future therapeutic option."

Experimental Biology and Medicine is a global journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership, visit http://www.sebm.org. Ifinterested in publishing in the journal, please visit http://ebm.sagepub.com.

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Axovant Presents First Evidence of Clinical Stabilization in Tay-Sachs Disease at the European Society of Gene and Cell Therapy 27th Annual Congress -…

NEW YORK and BASEL, Switzerland, Oct. 23, 2019 (GLOBE NEWSWIRE) -- Axovant Gene Therapies Ltd. (NASDAQ: AXGT), a clinical-stage company developing innovative gene therapies, today announced preliminary data from an expanded access study administering investigational AXO-AAV-GM2 gene therapy in two patients with infantile Tay-Sachs disease (TSD) at the 27th Annual Congress of the European Society of Gene and Cell Therapy. Infantile TSD, a rapidly progressive and fatal pediatric neurodegenerative genetic disorder, has a median life expectancy of approximately 3-4 years. This data indicates the potential to modify the rate of disease progression in children with infantile TSD.

Todays exciting clinical results from the AXO-AAV-GM2 program are the first reported evidence for potential disease modification in Tay-Sachs disease, and suggest an opportunity for gene replacement therapy to improve outcomes for children with this devastating condition, said Dr. Gavin Corcoran, chief R&D officer at Axovant. Myelination is an important component of healthy brain development in infants and is often abnormal in children with Tay-Sachs disease. We were encouraged to see MRI evidence of preserved brain architecture and improved myelination in the early symptomatic child treated at 10 months of age, coupled with stability of neuromuscular function as measured on the CHOP INTEND scale. We look forward to Dr. Terry Flottes presentation of this data at the ESGCT conference where he will describe these two clinical cases in detail.

Key findings from this first-in-human study in patients treated with AXO-AAV-GM2, an investigational gene therapy designed to restore -Hexosaminidase A enzyme activity in the central nervous system, include:

*CHOP INTEND is a 16-item scale of motor function that has been validated in infants with neuromuscular disorders. Items of motor function are graded from 0 to 4 for each item, where zero equals no response, and 4 equals a complete response. Change from baseline in total score of 4 points or a total score sustained > 40 points has been associated with a clinically meaningful benefit.

Dr. Terence Flotte, Professor of Pediatrics and Dean at the School of Medicine, University of Massachusetts Medical School, said, Bilateral intrathalamic and intrathecal delivery of rAAV gene therapy may surmount the obstacle of providing widespread distribution of therapeutic enzyme throughout the brain and CNS. This innovative delivery could overcome one of the primary challenges for developing treatments for Tay-Sachs, Sandhoff and many other severe pediatric genetic disorders, providing much needed hope for these families.

Dr. Flotte will present this data on AXO-AAV-GM2 in the First-in-Human gene therapy session on October 23, 2019 at 5:30 PM Central European Time (CET).

About AXO-AAV-GM2

AXO-AAV-GM2 is an investigational gene therapy for Tay-Sachs and Sandhoff disease, which rare and fatal pediatric neurodegenerative genetic disorders within the GM2 gangliosidosis family, caused by defects in theHEXA(leading to Tay-Sachs disease) orHEXB(leading to Sandhoff disease) genes that encode the two subunits of the -hexosaminidase A (HexA) enzyme. Both forms of GM2 gangliosidosis are caused by overwhelming storage of GM2 ganglioside within neurons throughout the central nervous system), which is normally degraded in the lysosome by the isozyme HexA. These genetic defects lead to progressive neurodegeneration and shortened life expectancy. AXO-AAV-GM2 aims to restore HexA levels by introducing a functional copy of theHEXAandHEXBgenes via delivery of two co-administered AAVrh8 vectors.

In 2018, Axovant licensed exclusive worldwide rights from the University of Massachusetts Medical School for the development and commercialization of gene therapy programs for GM1 gangliosidosis and GM2 gangliosidosis, including Tay-Sachs and Sandhoff diseases.

About Axovant Gene Therapies

Axovant Gene Therapies, part of the Roivant family of companies, is a clinical-stage gene therapy company focused on developing a pipeline of innovative product candidates for debilitating neurological and neuromuscular diseases. Our current pipeline of gene therapy candidates targets GM1 gangliosidosis, GM2 gangliosidosis (including Tay-Sachs disease and Sandhoff disease), and Parkinsons disease.

Axovant is focused on accelerating product candidates into and through clinical trials with a team of experts in gene therapy development and through external partnerships with leading gene therapy organizations. For more information, visitwww.axovant.com.

About Roivant

Roivantaims to improve health by rapidly delivering innovative medicines and technologies to patients.Roivantdoes this by buildingVants nimble, entrepreneurial biotech and healthcare companies with a unique approach to sourcing talent, aligning incentives, and deploying technology to drive greater efficiency in R&D and commercialization. Roivant today is comprised of a central technology-enabled platform and 20 Vants with over 45 investigational medicines in clinical and preclinical development and multiple healthcare technologies. For more information, please visitwww.roivant.com.

About the University of Massachusetts Medical School

The mission of the University of Massachusetts Medical School is to advance the health and well-being of the people of the commonwealth and the world through pioneering education, research, public service and health care delivery.

Research into potential therapies for lysosomal storage diseases such as Tay-Sachs, Sandhoff disease and GM1 gangliosidosis at UMass Medical School and Auburn University has led to significant advances in the field. Miguel Sena-Esteves, PhD, associate professor of neurology at UMass Medical School; Heather Gray-Edwards, PhD, DVM, formerly of Auburn and currently assistant professor of radiology at UMass Medical School; and Douglas Martin, PhD, professor of anatomy, physiology and pharmacology in the College of Veterinary Medicine and the Scott-Ritchey Research Center at Auburn University, have worked collaboratively for more than a decade on animal models and therapeutic approaches for these and similar disorders. For more information, visit http://www.umassmed.edu.

Forward Looking Statements and Information

This press release contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, might, will, would, should, expect, believe, estimate, and other similar expressions are intended to identify forward-looking statements. For example, all statements Axovant makes regarding the initiation, timing, progress, and reporting of results of its preclinical programs, clinical trials, and research and development programs; cash to be used in operating activities; its ability to advance its gene therapy product candidates into and successfully initiate, enroll, and complete clinical trials; the potential clinical utility of its product candidates; its ability to continue to develop its gene therapy platforms; its ability to develop and manufacture its products and successfully transition manufacturing processes; its ability to perform under existing collaborations with, among others, Oxford Biomedica, and theUniversity of Massachusetts Medical School, and to add new programs to its pipeline; its ability to enter into new partnerships or collaborations; its ability to retain and successfully integrate its leadership and personnel; and the timing or likelihood of its regulatory filings and approvals are forward-looking. All forward-looking statements are based on estimates and assumptions by Axovants management that, although Axovant believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Axovant expected.Such risks and uncertainties include, among others, the initiation and conduct of preclinical studies and clinical trials; the availability of data from clinical trials; the expectations for regulatory submissions and approvals; the continued development of its small molecule and gene therapy product candidates and platforms; Axovants scientific approach and general development progress; and the availability or commercial potential of Axovants product candidates. These statements are also subject to a number of material risks and uncertainties that are described in Axovants most recent Quarterly Report on Form 10-Q filed with theSecurities and Exchange CommissiononAugust 9, 2019, as updated by its subsequent filings with theSecurities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made.Axovant undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

Contacts:

Media and Investors

Parag MeswaniAxovant Gene Therapies(212) 547-2523investors@axovant.commedia@axovant.com

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Axovant Presents First Evidence of Clinical Stabilization in Tay-Sachs Disease at the European Society of Gene and Cell Therapy 27th Annual Congress -...

Physician-Scientist Christopher Haqq M.D., Ph.D. Joins Elicio Therapeutics as Research and Development Head – Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Elicio Therapeutics, a next generation immuno-oncology company, announced today that Christopher Haqq M.D., Ph.D. has joined Elicio as Executive Vice President, Head of Research and Development, and Chief Medical Officer.

Chris is an accomplished physician-scientist who brings to Elicio over 20 years of translational drug development and leadership in large and small biotechnology companies across T cell immunotherapy, biologic, and small molecule modalities, commented Elicio CEO Robert Connelly. We expect Chris knowledge of the impact of T-cell expansion, persistence and trafficking in immuno-oncology will dovetail with the unique lymph node targeting ability of Elicios Amphiphile platform.

Before joining Elicio, Dr. Haqq was the first employee and Chief Medical Officer of Atara Biotherapeutics, and later its Chief Scientific Officer, where he was the architect for an innovative pipeline including EBV specific T-cell product candidates for oncology and autoimmune disease, and a next generation off the shelf CAR-T cells for solid tumors. Earlier at Cougar Biotechnology and Janssen, Dr. Haqq was the lead clinician for a pivotal prostate cancer study leading to market approval for Zytiga (abiraterone acetate) and he led early development studies at Amgen.

Dr. Haqq has served as medical monitor for numerous oncology clinical trials working closely with global regulatory agencies. His teams have made successful filings for investigational new drug applications, breakthrough therapy, priority medicines, special protocol assessments and marketing approval and he has authored multiple patents and publications. Dr. Haqq initially practiced as a medical oncologist and led a translational science laboratory as an Assistant Professor in the Division of Hematology/Oncology at the University of California, San Francisco following post-graduate training as an Intern and Resident in Internal Medicine, Fellow in Medical Oncology and Fellow in Molecular Medicine. Dr. Haqq completed his M.D. and Ph.D. in Genetics at Harvard Medical School and his undergraduate training at Stanford University and the University of British Columbia.

I am excited to lead Elicios strong R&D team during the transition from the lab bench to the bedside for its promising lymph node targeted immunotherapies where preclinical monotherapy and CAR-T combination show unique potential, said Dr. Haqq. And as my family has experienced the unmet need for an effective mKRAS therapy, I am looking forward to evaluate ELI-002s safety and efficacy in mKRAS bearing pancreatic, colorectal and lung cancers.

About the Amphiphile Platform

The Elicio Amphiphile platform enables precise targeting and delivery of immunogens and cell-therapy activators directly to the lymphatic system, the brain center of the immune response, to significantly amplify and enhance the bodys own system of defenses, defeat solid and hematologic cancers, and prevent their recurrence. Once in the lymph nodes, Amphiphile immunotherapies are taken up by antigen presenting cells (APCs) to orchestrate signaling to natural or engineered immune cells in order to maximize therapeutic immune responses to disease. This strategy has been used to improve the activity of immunostimulatory agents, antigens, adjuvants, and cell-therapies that generate little to no response when used in the conventional forms. By precisely targeting these immunotherapies to the lymph nodes, Amphiphiles can unlock their full potential to generate and amplify anti-tumor immune responses. This substantially enhanced anti-tumor functionality and long-term protective memory may someday unlock the full potential of the immune response to eliminate cancer.

About Elicio Therapeutics

Elicio Therapeutics is committed to transforming the lives of patients and their families by re-engineering the bodys immune response to defeat cancer. By combining expertise in materials science and immunology, Elicio is engineering potent Amphiphile immunotherapies including lymph node targeted cell therapy activators, immunomodulators, adjuvants and vaccines for an array of aggressive cancers. Elicios lead Amphiphile vaccine targeting KRAS-driven cancers will begin initial patient studies in pancreatic in the first half of 2020. These programs are followed by a broad preclinical pipeline of lymph node targeted immunotherapies. For more information please visit http://www.elicio.com.

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Physician-Scientist Christopher Haqq M.D., Ph.D. Joins Elicio Therapeutics as Research and Development Head - Business Wire

Surgeon weighs in on textured breast implants – Washington University School of Medicine in St. Louis

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The implants are linked to anaplastic large-cell lymphoma, a rare cancer

Textured breast implants have been linked to a rare and sometimes fatal cancer known as anaplastic large-cell lymphoma. Shown are smooth and textured implants.

The Food and Drug Administration (FDA) announced Oct. 23 a recommendation that manufacturers of breast implants include a boxed warning on implant packaging about the risks associated with the devices, including complications that may require additional surgeries and the development of a rare, sometimes fatal cancer. This past summer Allergan, a global pharmaceutical company, voluntarily recalled its textured breast implants because of links to the cancer, called breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The cancer, a form of non-Hodgkin lymphoma, can reside in the scar tissue and fluid near the breast implant and spread throughout the body, compromising the immune system.

The American Society of Plastic Surgeons has reported 779 cases of BIA-ALCL and at least 33 deaths worldwide since the implants were introduced during the mid-1980s. However, the numbers may be higher because the most recent figures were documented Sept. 3. The majority of implants associated with the incidents were manufactured by Allergan. The cancer has occurred in women who received the implants for cosmetic breast enlargement and for reconstruction after mastectomy for breast cancer.

Similar health concerns have prompted recalls of textured breast implants in other countries.

In a commentary about textured breast implants, published Oct. 23 in JAMA Surgery, Terence M. Myckatyn, MD, a professor of surgery in the Division of Plastic and Reconstructive Surgery at Washington University School of Medicine in St. Louis, recommends smooth-surfaced breast implants for cosmetic and reconstructive patients in his practice.

In most cases, I believe that I can achieve equivalent results with either smooth or textured surface breast implants and that differential outcomes resulting from choosing one device over the other are imperceptible, Myckatyn, a co-author, wrote in the piece. I dont see the value in subjecting my patients to the risk of BIA-ALCL, even if it is only 1 in 3,000. Equally important, I dont see the value in subjecting them to increased anxiety related to their decision. That said, I recognize that there are specific situations where a textured breast implant may have value.

Myckatyn conducts research on textured breast implants and is the senior author of a study published recently in Natures Scientific Reports on breast implants associated with the rare lymphoma.

He shared his expertise:

What advice do you have for women with textured breast implants?

Women who have textured implants do not need them removed. However, they should be monitored at least once a year, and those with implants should immediately contact their physicians if they experience symptoms such as excessive fluid retention around the breast implant, pain, swelling, asymmetry, lumps in the breast or armpit, skin rash or hardening of the breast. Symptoms typically develop seven to nine years after the implant insertion.

It is important to note that women with these implants should not panic. This type of cancer is highly treatable, primarily by removing the implants and scar tissues. It also is very rare. There are several statistics from databases in different countries, but the lifetime risk has been estimated to be 1 in 30,000 women, to 1 in 1,000 women, to the most often cited 1 in 3,000 women. To put it in perspective, the lifetime risk of women developing breast cancer is 1 in 8.

Can you explain the differences between textured and smooth breast implants?

The shells of breast implants can have a textured or smooth surface. The filler can be either silicone or saline. But this is not a silicone versus saline issue. This type of cancer is associated with the breast implant shell. The shells can be round or shaped like a teardrop. Round implants are typically smooth. But all shaped implants have textured shells that act like Velcro to prevent the implant from slipping. The tissues grow into the pores of an implant and secure it from rotating on its axis. This is one of the main reasons for using textured implants. However, most plastic surgeons in the U.S., including myself, use the round, smooth-shell implants. Textured breast implants account for less than 10% of sales here compared with more than 80% of sales abroad. I almost exclusively use round breast implants because I can achieve desirable results with a smooth surface implant. Although the risk for breast-implant-associated lymphoma is rare, I see no reason to subject my patients to potential health risks or to increased anxiety. That said, in certain instances, a textured implant may have value. For example, patients who have issues with one of the breast implants becoming misshapen but not the other breast.

Talk about your recent study looking at texturized breast implants?

The cause of breast-implanted-associated lymphoma is unknown. In the U.S. and all over the world, there havent been many studies, and some of the research we reviewed had holes in the scientific methodology. However, the thought has been that the textured surfaces of the breast implants invite potentially harmful bacteria to thrive in the shells nooks and crannies. The one bacterium that has been implicated is called Ralstonia picketii.

With this as our backdrop, Washington University researchers and collaborators from the University of Texas Health Sciences Center in Houston decided to look at the microbiome. We found Ralstonia in tiny trace amounts, and it was just as likely to be found on the breasts of patients with the cancer as those without. Ralstonia was not in the top 100 organisms that we found. The breast is a gland, so we expected to find a lot of bacteria but we did not find a particular bacterium, or a class of bacteria, that could be associated with the lymphoma. I understand why that was a leading hypothesis. Some other cancers, such as gastric, are associated with a bacterium, and the cancer is treated by killing the bacteria. But that was not the case here.

Our findings are important because they show that unlike gastric cancers that can be prevented by eradicating certain bacteria with antibiotics, this rare lymphoma associated with textured breast implants cannot be prevented with antibiotics, but rather by avoiding textured surface breast implants.

Will you continue to study this problem?

We definitely plan to continue our research on this cancer. Some might think theres no need to bother because its a highly treatable, rare cancer, and these implants have been recalled from future implantation. But already theres been quite a bit of regulatory action, with the FDA and overseas in countries such as France and Denmark. Additionally, its important that we know the facts about the risk so we dont panic unnecessarily. One unfortunate result is that unsavory plastic surgeons may prey upon women with textured implants, urging them to undergo a surgical removal. As I mentioned, this is not recommended for asymptomatic women. However, surgery exposes the women to unnecessary health risks, such as infections, as well as the costs associated with the procedure.

What will you look at next?

Were looking at genetics. Specifically, were researching potential variations in the human genome that may cause the development of breast-implant-associated lymphoma.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Surgeon weighs in on textured breast implants - Washington University School of Medicine in St. Louis

What Is Going to Happen to Us? Inside ISIS Prison, Children Ask Their Fate – The New York Times

NORTHEASTERN SYRIA The prisoners cover the floor like a carpet of human despair. Many are missing eyes or limbs, some are bone-thin from sickness, and most wear orange jumpsuits similar to what the Islamic State, the terrorist group they once belonged to, dressed its own captives in before it killed them.

Upstairs, jammed into two cells with little sunlight, are more than 150 children ages roughly 9 to 14 from a range of countries. Their parents brought them to Syria and ended up dead or detained. The children have been here for months and have no idea where their relatives are or what the future holds.

I have a question, said a boy from Suriname inside his cell. What is going to happen to us? Are the kids going to come out?

Rare visits to two prisons for former residents of Islamic State-held territory in northeastern Syria by The New York Times this week laid bare the enormity of a growing legal and humanitarian crisis that the world has largely chosen to ignore.

As the Islamic State's self-declared caliphate collapsed in Syria, tens of thousands of men, women and children who had lived in it ended up in squalid camps and crowded prisons run by the Kurdish-led militia that had partnered with the United States to defeat the jihadists.

But now that a military incursion by Turkey against Kurdish forces has set off a new wave of violence and weakened their control over the area, uncertainty has grown over the fate of the huge population of people who survived the toppling of the Islamic State and have been warehoused since then in prisons and detention camps.

Most of their home countries have refused to take them back, fearing that they harbor extremist thoughts or could carry out attacks. So their governments have instead chosen to leave them in the custody of a Kurdish-led force that lacks the resources to house, feed and protect them, much less to investigate the adults and provide the children with education and rehabilitation.

Little about the minors conditions in the Kurdish-run prison appeared to meet international standards that, even for suspected criminals, prioritize children's well-being, consider detention a last resort and require specialized physical and emotional care.

One crowded cell held 86 minors from Syria, Iraq, Mauritius, Russia and elsewhere. Another held 67 adolescents and a boy who said he was 9 and from Russia.

When asked where his parents were, he shrugged and said, They got killed.

Later, he asked of his captors, Why dont they bring us fruit?

The confusion surrounding the detainees has only grown since President Trump started pulling United States forces out of the area, a decision that cleared the way for Turkey to begin its assault on Americas pivotal allies in the war against the Islamic State in Syria.

Prison crowding has increased because Kurdish fighters, who are viewed as a threat by Turkey, moved hundreds of prisoners away from the border to facilities farther from the battle zone, Kurdish officials said. And fighters who worked as prison guards have slipped off to the front lines to fight the Turks, leaving the facilities more vulnerable to prisoner uprisings or attacks by the Islamic State to free its comrades.

We are 100 percent sure that if they have the opportunity to escape from the prison, it will be very dangerous for us, said Can Polat, an assistant warden at a prison with more than 5,000 men. Holding these people here is not only a danger for Syria, it is a danger for the whole world.

The detention crisis in northeastern Syria is a bleak byproduct of the war against the Islamic State.

As the terrorist group was rolled back, losing its last patch of territory in Syria in March, Kurdish fighters found themselves in charge of about 11,000 men and tens of thousands of women and children. Many of them were foreigners, from Europe, Asia, Africa and the Arab world, and most of their countries refused to take them home, even to put them on trial, much less integrate them into society.

So with help from a United States-led international coalition, the Kurds established camps and a prison system, housing detainees in former government prisons they had taken over and in makeshift lock-ups in schools and other facilities.

Mr. Polats prison is a converted industrial institute that now holds more than 5,000 people. One-quarter of them are Syrians, the rest hailing from 29 other countries, including Iraq, Libya, Egypt, Afghanistan, the Netherlands and the United States.

The facility opened around the collapse of the Islamic State in Syria, which caused such an influx of prisoners that many were given orange jumpsuits provided by the coalition to replace their old clothes, Mr. Polat said.

Since the Islamic State often dressed its captives in orange before killing them, many of the captives gasped when they saw the new outfits, thinking they were about to be killed, too.

Orange jumpsuits now filled the prison. Most of the 400 men in a vast medical ward wore them. Many of them were sick or wounded. Men with metal braces holding broken bones in place lay on thin mattresses, while others shuffled to the bathroom on crutches or dragged their legs on the ground behind them.

A few were so emaciated that their cheekbones stuck out and their legs were as thin as arms. When one man made the call to prayer, many of the prisoners prayed sitting down because they were too injured or ill to stand.

The Kurdish guards assumed that most of the men had been fighters and still followed the Islamic States ideology, but the prisoners themselves played down their roles in the worlds most fearsome terrorist organization.

A Palestinian man with a broken leg said he had come to Syria because he wanted to help. A mechanic from Trinidad said he had not fought because he had been too busy fixing cars. A tall, muscular Russian said he had been a cook in an elementary school.

In dozens of interviews in two prisons, no one admitted to being a fighter.

Most wanted to return to their countries or hoped to get amnesty for renouncing the Islamic State.

There are some who say, I was a fighter and will continue on that path, and others who say, No, I was tricked, said Basil Karazoun, who said he had joined the terrorist group for protection after defecting from the Syrian military.

Like most of the prisoners, he feared being handed over to Syrias president, Bashar al-Assad, whose forces have been accused of widespread abuse and killings of detainees. After Mr. Trump announced that he was pulling troops out of Syria, the Kurds worried about being overrun by Turkey once the Americans abandoned them announced that they had reached an agreement to allow Syrian government forces into the area.

Its a fact that if we fall into the regimes hands, there will be mass executions, he said. That is how the regime thinks.

Another cell in the prison held 99 men, most of whom had lost limbs, including Abdelhamid al-Madioum, who described himself as an American who had lived near Minneapolis.

In an interview, he said he had worked at a Jamba Juice in high school, that his best friends were an atheist and a Christian, and that he had been studying engineering before joining the Islamic State in Syria, where he had hoped to study medicine.

But a few months after he arrived, he said, he was hit by an airstrike that shattered his body and tore off his right arm. Around the time he was captured by Kurdish fighters this year, he said, his wife was shot dead and he lost track of his two young sons, aged 2 and 4.

I made a mistake, he said. Ill admit it. Ill admit it 1,000 times.

It was unclear why some minors were put in prison, while most of the children of Islamic State fighters and followers have been taken to detention camps. Their cells were crowded, with no free space between their mattresses and blankets. When a guard swung open a hatch on the cells door, the children crowded around to peek outside.

Mr. Polat, the deputy warden, later said the authorities had indications that many of the minors had been through ideological training as cubs of the caliphate, or future fighters. Plans to move the youngest prisoners to rehabilitation centers had been delayed, he said, because of the Turkish incursion and the lack of international support.

Under United Nations standards for juvenile justice, even minors suspected of crimes should be detained only as a measure of last resort and for the shortest possible period of time, pending trial.

While the Islamic State did train boys for combat, it was unclear if that was true of the boys in the prison. None were awaiting trial, because the Syrian Kurdish authorities do not try foreigners.

The United Nations also says detained juveniles should receive all necessary individual assistance, including education, medical care and counseling.

The boys in prison said they received almost no services.

The situation is pretty bad here, so if they could hurry up and decide, said a 16-year-old boy from Mauritius. Months like this without knowing what is going to happen, people could start going crazy. They could say these guys were terrorists before with ISIS, but they are still human.

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What Is Going to Happen to Us? Inside ISIS Prison, Children Ask Their Fate - The New York Times

Scientists extend mice lifespan 12% by tweaking telomeres – Big Think

Scientists successfully extended the average lifespan of mice by breeding them using embryonic stem cells with extra-long telomeres. The findings are significant because the researchers managed to extend lifespan without genetic modification, and they also shed light on the aging process and techniques that might someday slow it.

The study published October 17 in Nature Communications focuses on telomeres, which are stretches of DNA found at the end of chromosomes.

Because telomeres protect the genetic material inside chromosomes, they've been likened to the plastic tips on the ends of shoelaces. But telomeres have also been compared to bomb fuses, or "molecular clocks," because they become shorter each time a cell divides, eventually shrinking so much that the cell dies or stops dividing. This shortening of our telomeres is associated with aging, cancer, and death.

"Telomere shortening is considered one of the hallmarks of aging as short telomeres are sufficient to cause organismal aging and decreased lifespan," the researchers wrote. "Telomere length is determined genetically and both average telomere length and the rate of telomere shortening varies between species. In this regard, humans are born with shorter telomeres than mice, but mice telomeres shorten 100-times faster than humans."

For years, scientists have been exploring how lengthening telomeres might help stave off disease and aging in animals, and, perhaps someday, in humans. But these attempts have all involved genetic modification. In the new study, a team of researchers at the Spanish National Cancer Research Center left induced stem cells to multiply in a petri dish, a process which eventually results in cells that have extra-long telomeres, as researchers first discovered in 2009.

Using these specially cultivated embryonic stem cells, the team generated mice with extra-long telomeres. Compared to a control group, these mice experienced "significant increase of 12.74 percent in median longevity", showed no cognitive defects and were less likely to develop cancer and obesity.

"This finding supports the idea that, when it comes to determining longevity, genes are not the only thing to consider," says molecular biologist Maria Blasco, from the Spanish National Cancer Research Centre (CNIO). "There is margin for extending life without altering the genes."

Shorter telomeres are linked to a shorter lifespan in humans. And although we're unlikely to see any experiments involving that are similar to the recent study, there are some steps you can take to lengthen your telomeres and increase your chances at a longer life. The main step: endurance exercise.

A 2018 study published in the European Heart Journal found that telomerase activity spikes in people who regularly do endurance exercises, defined as 45 minutes of continuous running. Interestingly, this effect was not observed in people who lifted weights or walked for 45 minutes. The results echoed those of a similar 2017 study, which found that people who ran regularly appeared to be biologically younger than those who didn't. But it takes some effort.

"If you want to see a real difference in slowing your biological aging, it appears that a little exercise won't cut it," study author Larry Tucker told Science Daily. "You have to work out regularly at high levels."

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Scientists extend mice lifespan 12% by tweaking telomeres - Big Think

Scientists Made Mice Live 12% Longer by Hacking Their Telomeres – Futurism

A team of researchers at the Spanish National Cancer Research Center have managed to extend the average lifespan of lab mice by more than 12 percent by cultivating embryonic cells in a special way,according to Science Alert no genetic modification required.

They looked at a natural process thats linked to aging: the strands of nucleotide sequences at the end of each chromosome, called telomeres,that act as a buffer to protect the genetic material inside the chromosomes. These telomeres tend get shorter over time as we age so longevity researchers have long pondered whether increasing their length could help us live longer.

In this case, the Spanish researchers left stem cells in a petri dish to multiply on their own, giving them unusually long telomeres. Mice bred with chromosomes featuring the twice-as-long telomeres showed a significant increase of 12.74 percent in median longevity, according to the researchers paper, which was published last week by the journal Nature Communications.

They also found that the specially-bred mice showed no difference in cognitive function, retained the longer telomeres over time, and were 20 percent less likely to develop age-related tumors.

The experiment isnt quite as revolutionary as it sounds this kind of technique isnt about to make humans live longer any time soon. But it could give scientists insight into the process of aging and perhaps find ways to slow it down in the future.

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Cesca Therapeutics Forms Joint Venture with Healthbanks Biotech (USA) to Provide Immune Cell Banking and Cell Processing Services – BioSpace

ImmuneCyte to Begin Operations in Fourth Quarter of 2019

RANCHO CORDOVA, Calif., Oct. 22, 2019 /PRNewswire/ -- Cesca Therapeutics Inc. (Nasdaq: KOOL), a market leader in automated cell processing and autologous cell therapies for regenerative medicine, and ThermoGenesis, its wholly owned device subsidiary, today announced that the company has entered into a definitive joint venture agreement with HealthBanks Biotech (USA) Inc., one of the world's leading stem cell bank networks, to commercialize its proprietary cell processing platform, CAR-TXpress, for use in immune cell banking as well as for cell-based contract development and manufacturing services (CMO/CDMO). The joint venture will be named ImmuneCyte Life Sciences Inc. ("ImmuneCyte") and is expected to officially launch during the fourth quarter of 2019.

Under terms of the agreement, ImmuneCyte will initially be owned 80% by HealthBanks Biotech and 20% by Cesca. Cesca will contribute to ImmuneCyte exclusive rights to use ThermoGenesis' proprietary cell processing technology for the immune cell banking business and non-exclusive rights for other cell-based contract development and manufacturing services. Cesca will also contribute its clinical development assets to the joint venture, as the company has decided to discontinue these activities in order to focus exclusively on the device business.

Once operational, ImmuneCyte will be among the first immune cell banks in the U.S. to provide clients with the opportunity to bank their own healthy immune cells for future use as a resource for cell-based immunotherapies, such as dendritic cell and chimeric antigen receptor (CAR) T-cell therapies. ImmuneCyte will utilize ThermoGenesis' proprietary CAR-TXpress platform which allows for the isolation of different components from 200 ml of blood in cGMP compliant, closed system. Given that the CAR-TXpress platform can increase cell processing efficiency by up to 16-fold as compared with the traditional, labor-intensive ficoll gradient centrifugation-based cell processing method, ImmuneCyte is expected to offer customers an unparalleled competitive advantage, including an ability to store their own immune cells at a tangibly lower cost.

"The ImmuneCyte joint venture will be paramount to the execution of our strategy to become a preferred cell processing and manufacturing solution provider in the cell and gene therapy field," said Dr. Chris Xu, Chairman and Chief Executive Officer of Cesca Therapeutics. "CAR-T therapeutic research is advancing rapidly. Partnering with HealthBanks Biotech, one of the foremost stem cell bank networks, with an experienced team and an established global infrastructure, will offer customers the ability to preserve younger, healthier and uncontaminated immune cells for potential future use. By applying our proprietary CAR-TXpress technology to immune cell banking and other CDMO cellular manufacturing services, we will allow for the manufacture and production of more effective and less costly immunotherapies."

In 2017, the U.S. Food and Drug Administration (FDA) approved two CAR-T cell therapies, under breakthrough designation, for the treatment of advanced B cell leukemia and lymphomas. Both use autologous (a patient's own) immune T cells to fight cancer and have reported an over 80% response rate in the "no-option" patient group, for those who have failed both chemo- and radiation therapies. This has helped to spur massive global interest for the development of additional CAR-T immunotherapies1. By the end of September 2019, there were over 800 CAR-T cell clinical trials registered on the http://www.clinicaltrials.gov website, targeting a wide variety of blood cancers and solid tumors.

Although highly effective, several recent studies on the eligibility of patients to enroll in CAR-T clinical trials showed that as many as 30-50% of cancer patients may not be eligible to enroll or to get sufficient CAR-T cells manufactured for the therapy. Reasons may include: (1) the function of the immune system declines with age and can be negatively affected by other medical conditions, (2) most standard cancer therapies, such as chemotherapy and radiation, destroy the immune system, and (3) in many cases of advanced cancer, cancer cells will enter circulation, invade and interfere with the body's natural production of immune cells. According to a recently reported JULIE trial, a CAR-T clinical trial in relapsed or refractory diffuse large B-cell lymphoma (DLBCL), one-third of the 238 screened patients failed to be enrolled, and more than half of the 238 failed to receive the intended CAR-T therapy2,3. ImmuneCyte will offer customers the ability to preserve younger, healthier and uncontaminated immune cells, for potential future use in advanced cancer immunotherapy.

About HealthBanks Biotech (USA) Inc.HealthBanks Biotech, headquartered in Irvine, CA, is one of the leading stem cell bank networks in the world and offers services globally through its sister companies located in the United States and other regions and nations. HealthBanks Biotech is accredited by the FDA, AABB, and CAP. The HealthBanks Biotech group was originally founded in 2001 with a vision that stem cells and cell and gene therapies could transform modern medicine. HealthBanks Biotech is a subsidiary of Boyalife Group, Inc. (USA), an affiliate of Boyalife (Hong Kong) Limited, the largest stockholder of Cesca. For more information about HealthBanks Biotech (USA) Inc., please visit: http://www.healthbanks.us.

About ImmuneCyte Life Sciences Inc.ImmuneCyte will provide clients with the opportunity to bank their own immune cells when the cells are "healthy and unaffected" as a future resource for cellular immunotherapies, such as CAR-T. ImmuneCyte utilizes a proprietary CAR-TXpress platform, a GMP compliant close-system capable of automated separating and cryopreserving different components from blood. For more information about ImmuneCyte Life Sciences Inc., please visit: http://www.immunecyte.com.

About Cesca Therapeutics Inc.Cesca Therapeutics develops, commercializes and markets a range of automated technologies for CAR-T and other cell-based therapies. Its device division, ThermoGenesis develops, commercializes and markets a full suite of solutions for automated clinical biobanking, point-of-care applications, and automation for immuno-oncology. The Company has developed a semi- automated, functionally closed CAR-TXpress platform to streamline the manufacturing process for the emerging CAR-T immunotherapy market. For more information about Cesca and ThermoGenesis, please visit: http://www.cescatherapeutics.com.

Company Contact:Wendy Samford916-858-5191ir@thermogenesis.com

Investor Contact:Paula Schwartz, Rx Communications917-322-2216pschwartz@rxir.com

References:

1. Facts About Chimeric Antigen Receptor (CAR) T-Cell Therapy, Leukemia and Lymphoma Society (2018). https://www.lls.org

2. Updated Analysis of JULIET Trial: Tisagenlecleucel in Relapsed or Refractory DLBCL (2018).

3. Eligibility Criteria for CAR-T Trials and Survival Rates in Chemorefractory DLBCL. Journal of Clinical Pathways (2018).

View original content:http://www.prnewswire.com/news-releases/cesca-therapeutics-forms-joint-venture-with-healthbanks-biotech-usa-to-provide-immune-cell-banking-and-cell-processing-services-300942618.html

SOURCE Cesca Therapeutics Inc.

Company Codes: NASDAQ-SMALL:KOOL

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Cesca Therapeutics Forms Joint Venture with Healthbanks Biotech (USA) to Provide Immune Cell Banking and Cell Processing Services - BioSpace

Engineered cell-based therapy as a new treatment strategy for type 1 diabetes – Medical News Bulletin

Cell-based therapy for type 1 diabetes is a new treatment strategy that is showing promising results. Type 1 diabetes is a chronic disease that can develop early in life. The disease involves the destruction of pancreatic beta cells by the bodys auto-immune response resulting in insufficient insulin production to regulate blood glucose. If left untreated, this condition can lead to serious long-term effects such as neuropathy, retinopathy, and renal failure. Insulin therapy is the current standard of care treatment of type 1 diabetes. However, insulin therapy cannot fully prevent the long-term complications associated with type 1 diabetes.

Organoids are tiny, three-dimensional tissue cultures that are derived from stem cells. Organoids can be created to replicate the complexity of an organ or they can be crafted to express selected aspects of an organ such as producing only certain types of cells.

Researchers have created organoids that differentiate into insulin-producing pancreatic cells. These modified insulin-producing cells successfully regulated blood glucose levels when implanted in diabetic mice.

The cluster of cells in the pancreas that produce insulin is known as islets. Islet cell transplantation is a powerful tool to treat type 1 diabetes. Many studies have shown how this cell therapy could be effective in the treatment of diabetes if long-term control of glucose levels can be achieved.

Researchers have faced challenges in this treatment strategy due to loss of islet cells after the transplantation. The loss of cells occurs mainly because of inflammation of the transplant site and revascularization of cells that disrupts blood and oxygen supply leading to cell death. Scientists are looking for new strategies that can prevent the loss of islet cells and improve clinical islet transplantation outcomes.

Amniotic epithelial cells are stem cells that have a high proliferative capacity, self-renewal ability, multilineage differentiation, ease of access, and are safe for transplantation. During the last few years, human amniotic epithelial cells have been of great interest to researchers working on regenerative medicine.

In a new study recently published in Nature Communications, researchers from Geneva, Switzerland, engineered viable and functional insulin-producing organoids by combining human amniotic epithelial cells and dissociated islet cells. The researchers tested if inclusion of human amniotic epithelial cells enhanced the engraftment and viability of islet cells and determined if this cell-therapy for type 1 diabetes was successful in mouse models. Various tests such as insulin expression, insulin secretion, and stability under hypoxic conditions were used to test the viability of the organoids.

The organoids composed of human amniotic epithelial cells and islet cells did not experience any islet loss post transplantation. The researchers observed a clear protective effect of amniotic epithelial cells on islet cells in conditions of hypoxia. In addition, the organoids maintained responsiveness to glucose and showed significant protection from cell death.

The researchers found that islet organoids enriched with human amniotic epithelial cells resulted in mass engraftment of insulin producing beta cells thus improving function of these cells. Compared with islet cell organoids not combined with amniotic epithelial cells, the organoids with islet cells and amniotic epithelial cell combination normalized the blood glucose levels in diabetic mice. This suggests that there was adequate blood glucose regulation achieved by these engineered organoids.

These findings show that combining islet cells with human amniotic epithelial cells markedly improves their functionality and viability of islet cells. It also helps in the successful engraftment of islet cells. This cell therapy for type 1 diabetes has the potential to be the next treatment strategy for this condition.

The researchers express the need to further explore the use of these organoids to include more favorable implantation sites and expanding to the use of stem cells that are an unlimited source of insulin.

Written by Preeti Paul, M.Sc.

Reference: Fanny Lebreton et al., Insulin producing organoids engineered from islet and amniotic epithelial cells to treat diabetes. Nature Communications 10, Article number: 4491 (2019)

Image bySteve BuissinnefromPixabay

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Do transhumanists need their own bill of rights? – Quartz

In todays future-facing era, phenomena once relegated to the world of science fiction are starting to edge their way into reality.

We have scientists growing brains from stem cells in petri dishes; robots are being granted national citizenship; virtual intelligences experience and expressanger.

For the past 50 years, the microprocessorthe chip that processes information in a computerhas doubled in capacity at least everyyear to two years. Experts predict that machine intelligence will be smarter than humans by 2030.

So heres my question: When the machines weve created possesses an intelligence that equals ours, will they deserve our protection?

Will they desire it? Maybe even demand it?

This should be your question, too. Because in a little longer than a decades time, well need answers if want to avert moral and civil rights mishaps.

Futurists and technologists have been working to prepare the world for radical new sapient technologies and intelligences with publications such as the Cyborg Bill of Rights V1.0 which advocates equality for mutants.

Beyond the microprocessor, instrumental in catapulting machine intelligence to new levels through its ever-increasing speed for calculations, weve seen accelerating advances in genetic editing, stem-cell research, and 3D bioprinting, each which will help to create entities that have both consciousness and intelligence. This year 3D bioprinting has come so far that a team of Israeli scientists were able to successfully print part of a human heart.

Netflix released a popular four-part documentary series called Unnatural Selection on the topic.

Scientists are already wading into murky waters when it comes to the rights of these new intelligent organisms that we create. AtYale University brains from deceased pigs are being stimulated in a vat, which has prompted controversy in the animal rights world.

Do the brains of these animals, once dead, now represent live animals? And if so, do they receive the same legal rights that have informed laws that protect animals against harmful animal testing and animal cruelty?

As a result of these emerging ethical issues, were seeing more debates about new terms of futurist-oriented rights.

But the fact remains that there are few, if any, actual rules for most of our new scientific realities.

This is largely what inspired me to come up with theTranshumanist Bill of Rights, which Wiredpublished in full in 2018. The document recently underwent its third rendition via crowdsourcing.

When the machines weve created possesses an intelligence that equals ours, will they deserve our protection?

Like many of the cyborg bills that existthere are about half a dozen significant ones floating around the internetthis bill includes legal protections for thinking robots, gender explanations for virtual intelligences, laws for genetically engineered sapient creatures, defense of freedoms allowing biohackers to modify their bodies, and many other protections. It even includes policies to fight off environmental destruction and planetary existential threats such as asteroids, plagues, nuclear war, and global warming.

In 2015, Iwalked up to the US Capitol building holdinga single-page print out of the document I had written. The machine gun-toting police standing guard just feet away from me threatened arrest, but there was little need; the taped-on page quickly fell off the building, fluttered off the wall in the wind.

I wasnt arrested. The police and journalists surrounding me chuckled at the bungled ceremonial moment.

I recall that I couldnt help but smile myself at the idea of getting a futurist bill of rights to become a fixed part of US governing policy at the time.

But four years later, with machines showing ever increasing sophisticationhumans are even marrying robotsin some parts of the worlda bill of rights is not as wild as it once sounded. We could easily say the same for genetically-modified babies being born, which happened for the first time inChinalast year.

In my work, I meet with people around the world who are interested in answering not if we need a futurist bill of rights, but when we will need it, from Harvard Universitys Kennedy School of Government to theCato Institute to theWorld Economic Forumto European ministries.

If you look through the various cyborg-inspired bills of rights already out there, youll find that a major goal is to include cyborg and transhumanist rights in the UNs 1948Universal Declaration of Human Rights one day.

The ideas of personhood, a right to education, and freedom of speech were once considered unattainable in some countries. Now these basic human rights are common, and at least some of this change is due to the powerful legal influence of the UNs universal bill, often seen as a blueprint for governments and laws around the globe.

Interestingly, one of the challenges of getting a transhumanist bill of rights taken seriously comes from minorities groups, when its perceived that futurist rights will undermine movements of historically marginalized peoples. While plenty of transhumanists are members of the LGBTQ community, the community has been reluctant to wander intofuturist LGBTQissues, such as nongender roleplaying as different species in virtual environments.

LGBTQ friends of minewhile often sympathetic to transhumanist goalshave told me that they believe that after their historic quest for rights in America especially, they still need to focus on progress for their own movement and its goals. They perceive a futurist bill of rights as a distraction.

I respect and agree with this. Minorities in the US and around the world face social discrimination and violations of rights that warrant our attention. But it wont slow down the trajectory of radical technologies, which is spurring a growing futurist community to call for its own set of rights, rules, and protections.

I understand that at times it seems preposterous to believe the world will need to consider whether super intelligentrobots can vote, or whether human heads can betransplantedto waiting tech-engineered bodies, or if four years of college education canbe downloadedinto human brains.

But these realities are likely to occur long before the century is out.

If society doesnt accept that new sapient lifeformswhether its an autonomous digital avatar living in a supercomputer, or a biological creature with human-level intelligence that genetic editing createdalso need rights, or that new forms of engineered conscious intelligences will walk among humans on Earth as a result of scientific progress, society will undergo another wave of civil strife as we scramble to play catch-up to whats fair and moral.

At the very least, societies and governments need more comprehensive plans to formally deal with these new realities. That begins with a Congressional dialogue and forming preliminary legal documents outlining potential rights for the evolving future.

Ultimately, it comes down to how humans believe new intelligent life deserves to be treated.

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Do transhumanists need their own bill of rights? - Quartz