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At 16, shes a pioneer in the fight to cure sickle cell disease at Boston Childrens – Boston.com

BOSTON Helen Obando, a shy slip of a girl, lay curled in a hospital bed in June waiting for a bag of stem cells from her bone marrow, modified by gene therapy, to start dripping into her chest.

The hope was that the treatment would cure her of sickle cell disease, an inherited blood disorder that can cause excruciating pain, organ damage and early death.

Helen, who at 16 was the youngest person ever to undergo the therapy, was sound asleep for the big moment.

It was a critical moment in medical science.

For more than a half-century, scientists have known the cause of sickle cell disease: A single mutation in a gene turns red blood cells into rigid crescent or sickle shapes instead of soft discs. These misshapen cells get stuck in veins and arteries, blocking the flow of blood that carries life-giving oxygen to the body and causing the diseases horrifying hallmark: episodes of agony that begin in babyhood.

Millions of people globally, a vast majority of them Africans, suffer from sickle cell disease. Researchers have worked for decades on improving treatment and finding a cure, but experts said the effort has been hindered by chronic underfunding, in part because most of the estimated 100,000 people in the United States who have the disease are African American, often poor or of modest means.

The disease also affects people with southern European, Middle Eastern or Asian backgrounds, or those who are Hispanic, like Helen.

This is the story of two quests for a sickle cell cure one by the Obando family and one by a determined scientist at Boston Childrens Hospital, Dr. Stuart Orkin, 73, who has labored against the disease since he was a medical resident in the 1970s.

Like many others affected by sickle cell, the Obando family faced a double whammy: not one but two children with the disease, Helen and her older sister, Haylee Obando. They lived with one hope for a cure, a dangerous and sometimes fatal bone marrow transplant usually reserved for those with a healthy sibling as a match. But then they heard about a potential breakthrough: a complex procedure to flip a genetic switch so the body produces healthy blood.

Scientists have been experimenting with gene therapy for two decades, with mixed success. And it will be years before they know if this new procedure is effective in the long term. But if it is, sickle cell disease could be the first common genetic disorder to be cured by manipulating human DNA.

Four weeks after the infusion of stem cells, Helen was strong enough to be discharged. At home, in Lawrence, Massachusetts, on a sofa with her mother by her side, she put a hand over her eyes and started to sob. She and her family wondered: Would it work? Was her suffering really over?

A Familys Nightmare

Sheila Cintron, 35, and Byron Obando, 40, met when she was in the eighth grade and he was a high school senior. They fell in love. Haylee, their first child, was born in 2001, when Cintron was 17.

When a newborn screening test showed that Haylee had the disease, her father asked, Whats sickle cell?

They soon found out.

As the family gathered for her first birthday party, Haylee started screaming inconsolably. They rushed her to the hospital. It was the first of many pain crises.

Doctors warned the parents that if they had another baby, the odds were 1 in 4 that the child would have sickle cell, too. But they decided to take the chance.

Less than two years later, Helen was born. As bad as Haylees disease was, Helens was much worse. When she was 9 months old, a severe blockage of blood flow in her pelvis destroyed bone. At age 2, her spleen, which helps fight bacterial infections, became dangerously enlarged because of blocked blood flow. Doctors surgically removed the organ.

After Helen was born, her parents decided not to have any more children. But four years later, Cintron discovered she was pregnant again.

But they were lucky. Their third child, Ryan Obando, did not inherit the sickle cell mutation.

As Ryan grew up, Helens health worsened. When he was 9, Helens doctors suggested a drastic solution: If Ryan was a match for her, he might be able to cure her by giving her some of his bone marrow, though there would also be major risks for her, including death from severe infections or serious damage to organs if his immune system attacked her body.

As it turned out, Ryan matched not Helen but Haylee.

The transplant succeeded, but her parents asked themselves how they could stand by while one daughter was cured and the sicker one continued to suffer.

There was only one way to get a sibling donor for Helen: have another baby. In 2017, the couple embarked on another grueling medical journey.

Obando had a vasectomy, so doctors had to surgically extract his sperm from his testicles. Cintron had 75 eggs removed from her ovaries and fertilized with her husbands sperm. The result was more than 30 embryos.

Not a single embryo was both free of the sickle cell gene and a match for Helen.

So the family decided to move to Mesa, Arizona, from Lawrence, where the cold, which set off pain crises, kept Helen indoors all winter. The family had already sold their house when they heard that doctors at Boston Childrens were working on sickle cell gene therapy.

Cintron approached Dr. Erica Esrick, a principal investigator for the trial. But the trial wasnt yet open to children.

Figuring Out the Science

Nothing had prepared Orkin for the suffering he witnessed in his 30s as a medical resident in the pediatric hematology ward at Boston Childrens. It was the 1970s, and the beds were filled with children who had sickle cell crying in pain.

Orkin knew there was a solution to the puzzle of sickle cell, at least in theory: Fetuses make hemoglobin the oxygen-carrying molecules in blood cells with a different gene. Blood cells filled with fetal hemoglobin do not sickle. But the fetal gene is turned off after a baby is born, and an adult hemoglobin gene takes over. If the adult gene is mutated, red cells sickle.

Researchers had to figure out how to switch hemoglobin production to the fetal form. No one knew how to do that.

Orkin needed ideas. Supported by the National Institutes of Health and Howard Hughes Medical Institute, he kept looking.

The breakthrough came in 2008. The cost of gene sequencing was plummeting, and scientists were finding millions of genetic signposts on human DNA, allowing them to home in on small genetic differences among individuals. Researchers started doing large-scale DNA scans of populations, looking for tiny but significant changes in genes. They asked: Was there a molecular switch that flipped cells from making fetal to adult hemoglobin? And if there was, could the switch be flipped back?

They found a promising lead: an unprepossessing gene called BCL11A.

In a lab experiment, researchers blocked this gene and discovered that the blood cells in petri dishes started making fetal instead of adult hemoglobin.

Next they tried blocking the gene in mice genetically engineered to have human hemoglobin and sickle cell disease. Again, it worked.

Patients came next, in the gene therapy trial at Boston Childrens that began in 2018.

The trial run by Dr. David Williams, an expert in the biology of blood-forming stem cells at Boston Childrens, and Esrick has a straightforward goal: Were going to reeducate the blood cells and make them think they are still in the fetus, Williams said.

Doctors gave adult patients a drug that loosened stem cells immature cells that can turn into red blood cells from the bone marrow, their normal home, so they floated free in the bloodstream. Then they extracted those stem cells from whole blood drawn from the patient.

The researchers used a disabled genetically engineered AIDS virus to carry information into the stem cells, flipping on the fetal hemoglobin gene and turning off the adult gene. Then they infused the treated stem cells into patients veins. From there, the treated cells migrated into the patients bone marrow, where they began making healthy blood cells.

With the success in adults, the Food and Drug Administration said Boston Childrens could move on to teenagers.

When her mother told her about the gene therapy trial, Helen was frightened. But the more she thought about it, the more she was ready to take the risk.

In the months after the gene therapy infusion at Boston Childrens, her symptoms disappeared.

Helen was scheduled for her six-month checkup Dec. 16. Helens total hemoglobin level was so high it was nearly normal a level she had never before achieved, even with blood transfusions. She had no signs of sickle cell disease.

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Ask the Expert: What are the most common types of brain tumors in children? – The Daily Progress

What are the most common types of brain tumors in children, and what treatment options are available?

Brain tumors are the most common solid tumors affecting children, with approximately 4,500 new cases each year in the U.S.

As brain tumors expand or block the normal pathways in the brain, the pressures inside the skull expand. As a result, symptoms of brain tumors can include headaches, seizures, lethargy, nausea and vomiting. A child experiencing progressively worsening symptoms like these should be evaluated by a pediatrician or in the emergency room. The doctors evaluation may include a scan of the brain. If the scan shows a tumor, the next step is a consultation with a neurosurgeon.

The majority of pediatric brain tumors occur in the posterior fossa (located near the bottom of the skull and the brain stem). The most common tumors include medulloblastoma, pilocytic astrocytoma, and ependymoma. Other less common tumors can occur in the cerebral hemispheres (the two main portions of the brain) and include astrocytomas, gangliogliomas, craniopharyngiomas, and germ cell tumors.

Surgery is usually the first step in treatment when a brain tumor is discovered. The goals of surgery are to determine whether the tumor is cancerous and remove all or as much of the tumor as safely as possible. At UVa Childrens Hospital, the latest technologies are utilized to help perform surgery, including intraoperative MRI, navigation, ultrasound and minimally invasive endoscopic surgery. Based on the types of cells found in the brain tumor, additional treatments may be needed. These therapies may include chemotherapy, radiation therapy, proton therapy, stem cell rescue and bone marrow transplantation and/or supportive care for rehabilitation.

More recent treatment options have focused on precision medicine and targeted drug therapy. Targeted drug treatments can cause brain tumor cells to die by blocking abnormalities present within these cells. These drugs are changing how brain tumors are treated while improving outcomes. Current research is focused on understanding the molecular basis of tumor formation and discovery of new targets for treatment.

At UVa, we are committed to providing the best neurosurgical care for children through our multidisciplinary brain tumor team, consisting of neurosurgery, neurology, pediatric oncology and radiation oncology.

For more information, visit childrens.uvahealth.com/services/pediatric-neurosurgery.

Dr. Hasan R. Syed and Dr. John Jane Jr. are pediatric neurosurgeons at UVa Childrens Hospital.

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Ask the Expert: What are the most common types of brain tumors in children? - The Daily Progress

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What is Mantle Cell Lymphoma and How Is It Treated? – Dana-Farber Cancer Institute

Last Updated on January 10, 2020

Medically reviewed by Ann S. LaCasce, MD, MMSc

Mantle cell lymphoma is a rare, often aggressive form of non-Hodgkin lymphoma (NHL), a cancer that involves white blood cells known as lymphocytes, which help protect the body from disease. It is named for its origins in the mantle zone a ring of cells within the lymph nodes where B cells (a type of lymphocyte) grow and take on specialized functions. It comprises about 6% of all cases of NHL, usually arises during an individuals early 60s, and is more common in men than women.

The most common symptoms of mantle cell lymphoma include:

At the time of diagnosis,nearly all patients have disease that has spread beyond its initial site.

For most patients, the cause of the disease is unknown, but rates are higher among farmers and people from rural areas.

Itoccurs when B lymphocytes acquire genetic mutations that alter their functionand growth. One such abnormality, found in 90% of cases, causes B lymphocytesto overproduce cyclin D1, a protein that spurs the cells growth. Othermutations can interfere with B cells ability to produce infection-fightingantibodies, leaving patients vulnerable to certain diseases.

A definitive diagnosis requires a biopsy of an affected lymph node or other involved tissue.

Doctors use a variety of scans to determine the diseases stage, or how far it has advanced. These include:

Treatment for mantle cell lymphoma varies depending on patients age and overall health and the stage of the disease. Patients who have yet to develop symptoms and who have a relatively small amount of slow-growing disease may be recommended for active surveillance close monitoring of their health through regular checkups and lab tests. When lymphoma-related symptoms appear or tests show a worsening of the disease, active treatment may begin.

The initial treatment for aggressive mantle cell lymphoma in younger patients often includes a combination of chemotherapy drugs in conjunction with an antibody-based treatment, often followed by a stem cell transplant using patients own stem cells. Older, less-fit patients may undergo less intensive chemotherapy sometimes followed by a prolonged course of antibody therapy.

Other treatments may include drugs known as BTK inhibitors such as acalbrutinib and ibrutinib, which interfere with lymphoma cells internal growth signals.

In patients who relapse after treatment or dont respond to initial treatment, a variety of options may be available, including:

Clinical trials are currently underway of CAR T-cell therapy for patients with mantle cell lymphoma. The therapy, which uses genetically modified immune system T cells to attack tumor cells, has been shown to be effective in patients with other forms of non-Hodgkin lymphoma. Other trials are testing drugs known as bispecific antibodies, artificial proteins that can bind simultaneously to two surface proteins on cells, and targeted agents directed against specific cancer-related proteins.

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Stem Cell Therapy Market 2020 Analysis Focusing On Top Companies- Osiris Therapeutics, Medipost Co., Anterogen Co., Pharmicell Co. – BulletintheNews

New Jersey, United States, The report titled Stem Cell Therapy Market is one of the most comprehensive and important additions to Verified Market Researchs archive of market research studies. It offers detailed research and analysis of key aspects of the Stem Cell Therapy market. The market analysts authoring this report have provided in-depth information on leading growth drivers, restraints, challenges, trends, and opportunities to offer a complete analysis of the Stem Cell Therapy market. Market participants can use the analysis on market dynamics to plan effective growth strategies and prepare for future challenges beforehand. Each trend of the Stem Cell Therapy market is carefully analyzed and researched about by the market analysts.

Global Stem Cell TherapyMarketwas valued at USD 86.62 million in 2016 and is projected to reach USD 221.03million by 2025, growing at a CAGR of 10.97% from 2017 to 2025.

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Top 10 Companies in the Global Stem Cell Therapy Market Research Report:

Global Stem Cell Therapy Market: Competitive Landscape

Competitive landscape of a market explains strategies incorporated by key players of the market. Key developments and shift in management in the recent years by players has been explained through company profiling. This helps readers to understand the trends that will accelerate the growth of market. It also includes investment strategies, marketing strategies, and product development plans adopted by major players of the market. The market forecast will help readers make better investments.

Global Stem Cell Therapy Market: Segment Analysis

This section of the report includes segmentation such as application, product type, and end user. These segmentations aid in determining parts of market that will progress more than others. The segmentation analysis provides information about the key elements that are thriving the specific segments better than others. It helps readers to understand strategies to make sound investments. The Global Stem Cell Therapy Market is segmented on the basis of product type, applications, and its end users.

Global Stem Cell Therapy Market: Regional Analysis

This part of the report includes detailed information of the market in different regions. Each region offers different scope to the market as each region has different government policy and other factors. The regions included in the report are North America, South America, Europe, Asia Pacific, and the Middle East. Information about different region helps the reader to understand global market better.

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Table of Content

1 Introduction of Stem Cell Therapy Market

1.1 Overview of the Market 1.2 Scope of Report 1.3 Assumptions

2 Executive Summary

3 Research Methodology of Verified Market Research

3.1 Data Mining 3.2 Validation 3.3 Primary Interviews 3.4 List of Data Sources

4 Stem Cell Therapy Market Outlook

4.1 Overview 4.2 Market Dynamics 4.2.1 Drivers 4.2.2 Restraints 4.2.3 Opportunities 4.3 Porters Five Force Model 4.4 Value Chain Analysis

5 Stem Cell Therapy Market, By Deployment Model

5.1 Overview

6 Stem Cell Therapy Market, By Solution

6.1 Overview

7 Stem Cell Therapy Market, By Vertical

7.1 Overview

8 Stem Cell Therapy Market, By Geography

8.1 Overview 8.2 North America 8.2.1 U.S. 8.2.2 Canada 8.2.3 Mexico 8.3 Europe 8.3.1 Germany 8.3.2 U.K. 8.3.3 France 8.3.4 Rest of Europe 8.4 Asia Pacific 8.4.1 China 8.4.2 Japan 8.4.3 India 8.4.4 Rest of Asia Pacific 8.5 Rest of the World 8.5.1 Latin America 8.5.2 Middle East

9 Stem Cell Therapy Market Competitive Landscape

9.1 Overview 9.2 Company Market Ranking 9.3 Key Development Strategies

10 Company Profiles

10.1.1 Overview 10.1.2 Financial Performance 10.1.3 Product Outlook 10.1.4 Key Developments

11 Appendix

11.1 Related Research

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Highlights of Report

About Us:

Verified market research partners with clients to provide insight into strategic and growth analytics; data that help achieve business goals and targets. Our core values include trust, integrity, and authenticity for our clients.

Analysts with high expertise in data gathering and governance utilize industry techniques to collate and examine data at all stages. Our analysts are trained to combine modern data collection techniques, superior research methodology, subject expertise and years of collective experience to produce informative and accurate research reports.

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Stem Cell Therapy Market 2020 Analysis Focusing On Top Companies- Osiris Therapeutics, Medipost Co., Anterogen Co., Pharmicell Co. - BulletintheNews

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Canine Stem Cell Therapy Market Will Make a Huge Impact in Near Future – Expert Recorder

A synopsis of the global canine stem cell therapy market with reference to the global healthcare pharmaceutical industry

Despite the economic and political uncertainty in the recent past, the global healthcare industry has been receiving positive nudges from reformative and technological disruptions in medical devices, pharmaceuticals and biotech, in-vitro diagnostics, and medical imaging. Key markets across the world are facing a massive rise in demand for critical care services that are pushing global healthcare spending levels to unimaginable limits.

A rapidly multiplying geriatric population; increasing prevalence of chronic ailments such as cancer and cardiac disease; growing awareness among patients; and heavy investments in clinical innovation are just some of the factors that are impacting the performance of the global healthcare industry. Proactive measures such as healthcare cost containment, primary care delivery, innovation in medical procedures (3-D printing, blockchain, and robotic surgery to name a few), safe and effective drug delivery, and well-defined healthcare regulatory compliance models are targeted at placing the sector on a high growth trajectory across key regional markets.

Parent Indicators Healthcare Current expenditure on health, % of gross domestic product Current expenditure on health, per capita, US$ purchasing power parities (current prices, current PPPs) Annual growth rate of current expenditure on health, per capita, in real terms Out-of-pocket expenditure, % of current expenditure on health Out-of-pocket expenditure, per capita, US$ purchasing power parity (current prices, current PPPs) Physicians, Density per 1000 population (head counts) Nurses, Density per 1000 population (head counts) Total hospital beds, per 1000 population Curative (acute) care beds, per 1000 population Medical technology, Magnetic Resonance Imaging units, total, per million population Medical technology, Computed Tomography scanners, total, per million population

Research Methodology

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XploreMR utilizes a triangulation methodology that is primarily based on experimental techniques such as patient-level data, to obtain precise market estimations and insights on Molecule and Drug Classes, API Formulations and preferred modes of administration. Bottom-up approach is always used to obtain insightful data for the specific country/regions. The country specific data is again analysed to derive data at a global level. This methodology ensures high quality and accuracy of information.

Secondary research is used at the initial phase to identify the age specific disease epidemiology, diagnosis rate and treatment pattern, as per disease indications. Each piece of information is eventually analysed during the entire research project which builds a strong base for the primary research information.

Primary research participants include demand-side users such as key opinion leaders, physicians, surgeons, nursing managers, clinical specialists who provide valuable insights on trends and clinical application of the drugs, key treatment patterns, adoption rate, and compliance rate.

Quantitative and qualitative assessment of basic factors driving demand, economic factors/cycles and growth rates and strategies utilized by key players in the market is analysed in detail while forecasting, in order to project Year-on-Year growth rates. These Y-o-Y growth projections are checked and aligned as per industry/product lifecycle and further utilized to develop market numbers at a holistic level.

On the other hand, we also analyse various companies annual reports, investor presentations, SEC filings, 10k reports and press release operating in this market segment to fetch substantial information about the market size, trends, opportunity, drivers, restraints and to analyse key players and their market shares. Key companies are segmented at Tier level based on their revenues, product portfolio and presence.

Please note that these are the partial steps that are being followed while developing the market size. Besides this, forecasting will be done based on our internal proprietary model which also uses different macro-economic factors such as per capita healthcare expenditure, disposable income, industry based demand driving factors impacting the market and its forecast trends apart from disease related factors.

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Standard Report Structure Executive Summary Market Definition Macro-economic analysis Parent Market Analysis Market Overview Forecast Factors Segmental Analysis and Forecast Regional Analysis Competition Analysis

Target Audience Production Companies Suppliers Channel Partners Marketing Authorities Subject Matter Experts Research Institutions Financial Institutions Market Consultants Government Authorities

Market Taxonomy

The global canine stem cell therapy market has been segmented into:

Product Type: Allogeneic Stem Cells Autologous Stem cells

Application: Arthritis Dysplasia Tendonitis Lameness Others

End User: Veterinary Hospitals Veterinary Clinics Veterinary Research Institutes

Region: North America Latin America Europe Asia Pacific Japan Middle East & Africa

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XploreMR is one of the worlds leading resellers of high-quality market research reports. We feature in-depth reports from some of the worlds most reputed market research companies and international organizations. We serve across a broad spectrum from Fortune 500 to small and medium businesses. Our clients trust us for our unwavering focus onquality and affordability. We believe high price should not be a bottleneck for organizations looking to gain access to quality information.

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Study protocol for a phase II, multicentre, prospective, non-randomised clinical trial to assess the safety and efficacy of infusing allogeneic…

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Study protocol for a phase II, multicentre, prospective, non-randomised clinical trial to assess the safety and efficacy of infusing allogeneic activated and expanded natural killer cells as consolidation therapy for paediatric acute myeloblastic leukaemia.

BMJ Open. 2020 Jan 08;10(1):e029642

Authors: Muoz Builes M, Vela Cuenca M, Fuster Soler JL, Astigarraga I, Pascual Martnez A, Vagace Valero JM, Tong HY, Valentn Quiroga J, Fernndez Casanova L, Escudero Lpez A, Sisinni L, Blanquer M, Mirones Aguilar I, Gonzlez Martnez B, Borobia AM, Prez-Martnez A

AbstractINTRODUCTION: Acute myeloblastic leukaemia (AML) constitutes the second most common haematological malignancy in the paediatric population. Current treatment regimens are based on the administration of polychemotherapy, combining high doses of cytarabine with anthracyclines and topoisomerase inhibitors. Allogeneic haematopoietic stem cell transplantation (HSCT) is an option for high-risk patients with AML (and for intermediate-risk patients if a sibling donor is available). With this strategy, AML survival has increased substantially; however, it has remained stagnant at approximately 60%, with relapse being the principal culprit. The predominant role of the immune system and natural killer (NK) cells in controlling paediatric AML has gained importance within the context of HSCT. In this protocol, we propose incorporating this cell therapy as an adjuvant treatment through the infusion of activated and expanded haploidentical NK (NKAE) cells in paediatric patients with AML who are in cytological remission after completing consolidation therapy, and with no indication for HSCT.METHODS AND ANALYSIS: Patients up to 30 years of age, diagnosed with AML, in their first cytological remission, who have completed both the induction and the consolidation phases of chemotherapy and do not meet the criteria for allogeneic HSCT are eligible. The patients will receive two doses of NKAE cells once a week, using a GMP K562-mbIL15-41BBL stimulus from a haploidentical donor and interleukin 2 subcutaneously. The patients will then be followed up for 36 months to assess the primary endpoint, which is the probability of relapse after NK cell infusion.ETHICS AND DISSEMINATION: This clinical trial was approved by the Clinical Research Ethics Committee of La Paz University Hospital and The Spanish Agency of Medicines and Medical Devices. Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting.TRIAL REGISTRATION NUMBER: EudraCT code: 2015-001901-15, ClinicalTrials.gov Identifier: NCT02763475.

PMID: 31919123 [PubMed in process]

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Study protocol for a phase II, multicentre, prospective, non-randomised clinical trial to assess the safety and efficacy of infusing allogeneic...

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