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Making bone marrow transplants safer

New approach would use antibodies rather than radiation and chemotherapy June 7, 2016 | Editor's Pick Popular  By Hannah L. Robbins, Harvard Stem Cell Institute B.D. Colen/Harvard Stem Cell Institute Communications Rahul Palchaudhuri (left), postdoctoral fellow, and David Scadden, co-director of the Harvard Stem Cell Institute, look at real-time images of blood stem cells settling into bone marrow. Harvard Stem Cell Institute (HSCI) scientists have taken the first steps toward developing a treatment that would make bone marrow blood stem cell transplantation safer, and as a result, more widely available to the millions of people living with blood disorders such as sickle cell anemia, thalassemia, andAIDS. Bone marrow transplantation is the only curative therapy for these blood diseases. But for the new, transplanted stem cells to do their work, faulty stem cells must first be “evicted” or killed. Accomplishing that requires patients to endure chemotherapy and radiation, a vicious assault on the body with lifelong consequences. In a study recently published in the journal Nature Biotechnology, HSCI researchers at Harvard University and Massachusetts General Hospital (MGH), in collaboration with Boston Children’s Hospital and Dana-Farber Cancer Institute, all Harvard affiliates, have developed a nontoxic transplantation procedure using antibodies to specifically target blood stem cells in mice, an approach they hope will make blood stem cell transplants for these patients far less toxic. The new treatment removes more than 98 percent of blood stem cells, making it as effective as chemotherapy and radiation, researchers said. “Instead of using non-targeted drugs that have lots of collateral damage, we thought we could take advantage of the precision of the immune system, in particular antibodies,” said David Scadden, co-director of HSCI, the Gerald and Darlene Jordan Professor of Medicine, and [...]

Calgary doctors develop new stem-cell transplant procedure to cure children with sickle cell anemia

Published on: June 6, 2016 | Last Updated: June 6, 2016 7:23 PM MDT by Alia Dharssi Cardelia Fox, centre, with her sister Tamika Allen and Dr. Greg Guilcher at the Children's Hospital on Monday June 6, 2016. Cardelia suffered from sickle cell anemia and was treated by Dr. Guilcher with stem cells from her sister Tamika. MIKE DREW / POSTMEDIA When she was just six months old, Cardelia Fox had a stroke — the first of three she would experience as a child. At the time, doctors told her parents she wouldn’t live past five because she suffered from sickle cell anemia, a genetic blood disorder in which abnormal sickle-shaped red blood cells hinder the flow of oxygen through the body. Now 19, the bubbly Calgarian of Jamaican descent is cured of the disease thanks to a new stem-cell transplant procedure being spearheaded among children by the Alberta Children’s Hospital with potentially global implications. “It’s really a breakthrough,” said Anna Banerji, a pediatrician and professor at the University of Toronto. “This could make a huge difference in the life of a child.” To date, the hospital has successfully cured sickle cell anemia in nine children with a new protocol for stem-cell transplants, which involves a bone marrow donation from a sibling who is a 100 per cent match, but does not have sickle cell anemia. The odds a patient has such a sibling are one in five. Stem-cell transplants for children and teenagers with sickle cell anemia have grown increasingly common in recent years and are carried out in many hospitals in the U.S. and Europe, said George Buchanan, professor of pediatrics at the University of Texas Southwestern Medical Centre. But Alberta Children’s approach is unique because it is likely [...]

Researcher finds novel way to monitor serious blood disorder using a smart phone

Sept. 22, 2015 Eureka Alert! Gisele Galoustian Florida Atlantic University receives NSF grant A researcher from Florida Atlantic University has come up with a unique way to monitor sickle cell disease -- a serious blood disorder -- using a smart phone. With a $166,935 grant from the National Science Foundation, E. (Sarah) Du, Ph.D., assistant professor in the Department of Ocean and Mechanical Engineering in FAU's College of Engineering and Computer Science, and principal investigator, will develop a portable smart sensor and a phone application for patients to analyze and store the results of their blood tests on a smart phone. This technology will enable them to keep a close watch on any abnormal activities in their blood cells and take important steps to manage this disease with early intervention. Sickle cell disease is a hereditary blood disorder that affects red blood cells, distorting their natural disc shape into a crescent moon or "sickle" shape. Normal red blood cells move freely through small vessels throughout the body to deliver oxygen. With sickle cell disease, the misshapen red blood cells become hard and sticky, making it difficult for them to move through blood vessels. They eventually block the flow and break apart. This process results in a number of problems including severe chronic pain, stroke, organ damage, spleen dysfunction, heart failure and even death. "A major challenge in the management of sickle cell disease is the tremendous pain that patients endure from chronic and acute pain episodes called pain crisis," said Du. "Unfortunately, these pain episodes are unpredictable and patients never know when or where these episodes will take place." Integrating microfluidics with communication technologies like a smart phone, Du and her collaborators will create a disposable [...]

Lab-produced blood cells set for human trials in landmark project involving Cambridge scientists

CambridgeNews  |  Posted: June 25, 2015 By Freya Leng NHSBT Blood Van Cambridge scientists are involved in a landmark project that will see red blood cells produced in the laboratory transfused into humans by 2017, NHS Blood and Transplant has announced. The in-man clinical trials of manufactured blood form a key part of the blood and organ service's 2020 Research and Development programme. The plan outlines how NHS Blood and Transplant, in partnership with leading universities including Cambridge, will develop transfusion, transplantation and regenerative medicine over the next five years. Dr Nick Watkins, from the University of Cambridge and NHS Blood and Transplant Assistant Director of Research and Development said: "Scientists across the globe have been investigating for a number of years how to manufacture red blood cells to offer an alternative to donated blood to treat patients. We are confident that by 2017 our team will be ready to carry out the first early phase clinical trials in human volunteers. "These trials will compare manufactured cells with donated blood. The intention is not to replace blood donation but provide specialist treatment for specific patient groups. "Research has laid the foundation for current transfusion and transplantation practices. Continued investment in research and development is critical to our role in saving and improving lives through blood and organ donation. Our five-year research and development plan will ensure we advancetreatment of all who depend upon our products and services. "The manufactured red cell trials form part of our world-leading work in regenerative medicine and one of eight research goals for 2015-2020 that will bring long-term improvements for patients and donors." Scientists from NHS Blood and Transplant and the Universities of Bristol, Cambridge and Oxford - led by Prof [...]

MGH gives grant to low-cost sickle cell diagnostic

Mar 31, 2015 Jessica Bartlett Reporter-Boston Business Journal Massachusetts General Hospital’s Center for Global Health is helping to fund an affordable sickle cell diagnostic, awarding $100,000 to the Whitesides Research Group. Courtesy/Whitesides Research Group A density test can tell whether someone has sickle cell disease. The team, led by Harvard University Chemistry Professor George Whitesides, has been working on diagnostic for years, and has a prototype that has been tested in both the lab and in Zambia. The test currently costs 50 cents a piece, though engineers are hoping to make it cheaper The money, granted through the Consortium for Affordable Medical Technologies, will help engineers perfect the prototype, as well as ensure that the prototype functions within a larger manufacturing and shipping process. “We’re at a stage where we’re hoping to have a commercial partner soon and move forward on this,” said AJ Kumar, postdoctoral fellow and Whitesides Research Group member who is leading the sickle cell disease project. The diagnostic works by filtering blood into a solution that is able to parse out cells based on their density. Sickle cells, which are deformed red blood cells shaped like a C, are denser than normal red blood cells, and sink to the bottom of the solution. “The main goal is to identify people with sickle cell disease, but even if we can help with the screening process…that could also be a win,” Kumar said. Currently, sickle cell disease affects more than 300,000 newborns every year, most in sub-Saharan Africa and India. Timely diagnosis can be difficult due to out of hospital births, a lack of reliable electricity and a shortage of trained personnel. An affordable diagnostic would help children get the care they need before they suffer [...]

Sickle Cell Drug Offers “Overwhelming” Gains as “Exciting” Stem Cell Trial Starts

Mon, 03/16/2015 - 3:58pm Cynthia Fox, Science Editor Normal blood cells next to a sickle-blood cell, colored scanning electron microscope image (Credit: OpenStax College)A clinical trial of the most common sickle cell anemia drug, hydroxyurea, was halted a year early this winter because of “overwhelming evidence of benefit,” reported University of Nebraska Medical Center pediatric researcher Stephen Obaro, M.D., Ph.D., in The Lancet.Hydroxyurea is “the only readily available disease-modifying therapy for patients with sickle cell,” Principal Investigator Russell Ware, M.D., Ph.D., told Drug Discovery & Development, so this was good news to patients and clinicians. Ware is director of hematology at the Cincinnati Children’s Hospital. “Recently published National Institutes of Health (NIH) evidence-based guidelines [also] suggest it should be used more often,” Ware added. But hydroxyurea does not solve all problems. It ultimately fails 50 percent of patients (if this number may drop with more widespread and knowledgeable use of the drug.) Average sickle cell patients only live into their 40s (if this number, too, could change with more widespread and knowledgeable use of the drug.) And while “[the drug] is widely available in the U.S. and Europe, it is not in low-resource countries,” Ware told Drug Discovery & Development. Given that two-thirds of the 305,800 newborns with sickle cell anemia live in Africa, this is one of many problems. So other approaches are being investigated globally, including a pioneering genetically engineered stem cell clinical trial that recently enrolled its first patient. Hydroxyurea Sickle cell anemia occurs as the result of an inherited mutation in the oxygen-carrying hemoglobin (Hbs) gene. This causes red blood cells to become sticky, and form a sickle shape, which impairs their ability to carry oxygen, and causes them to aggregate and form constant blockages [...]

Johns Hopkins researchers engineer custom blood cells

Step toward new treatment for patients with sickle cell disease March 9, 2015 JOHNS HOPKINS MEDICINE Researchers at Johns Hopkins have successfully corrected a genetic error in stem cells from patients with sickle cell disease, and then used those cells to grow mature red blood cells, they report. The study represents an important step toward more effectively treating certain patients with sickle cell disease who need frequent blood transfusions and currently have few options. The results appear in an upcoming issue of the journal Stem Cells. In sickle cell disease, a genetic variant causes patients' blood cells to take on a crescent, or sickle, shape, rather than the typical round shape. The crescent-shaped cells are sticky and can block blood flow through vessels, often causing great pain and fatigue. Getting a transplant of blood-making bone marrow can potentially cure the disease. But for patients who either cannot tolerate the transplant procedure, or whose transplants fail, the best option may be to receive regular blood transfusions from healthy donors with matched blood types. The problem, says Linzhao Cheng, Ph.D. , the Edythe Harris Lucas and Clara Lucas Lynn Professor of Hematology and a member of the Institute for Cell Engineering, is that over time, patients' bodies often begin to mount an immune response against the foreign blood. "Their bodies quickly kill off the blood cells, so they have to get transfusions more and more frequently," he says. A solution, Cheng and his colleagues thought, could be to grow blood cells in the lab that were matched to each patient's own genetic material and thus could evade the immune system. His research group had already devised a way to use stem cells to make human blood cells. [...]

Investigational Therapy Could Attack Cause of Sickle Cell Crises

Mar. 2, 2015 By Duke Medicine News and Communications DURHAM, N.C. – Treatment for painful episodes of blood vessel obstruction in sickle cell anemia is currently limited to controlling pain, but an investigational therapy might be able to interfere with the underlying cause of these events, known as vaso-occlusion crises, researchers at Duke Medicine report. In a small, multicenter patient study led by Marilyn J. Telen, M.D., Wellcome Professor of Medicine in the division of hematology at Duke University Medical School, patients who received an investigational drug had quicker resolution of the pain episode, although the difference compared to a control group did not rise to statistical significance. Telen said the study’s small size, as well as the wide variability in the length of time that all of the study patients suffered painful vascular obstruction, contributed to the statistical draw. A larger, international study is planned to begin later this year to provide greater clarity. Patients who received the investigational drug also used far less pain medication, which was self-administered. Those findings were statistically significant. The findings were reported online March 2, 2015, in the journal Blood. “We have not had good therapies for people with this disease,” Telen said. “But this approach shows more promise than anything else I’ve seen in 34 years of treating sickle cell disease.” Sickle cell anemia is a genetic condition in which some of the red blood cells are stiff and shaped like crescents, or sickles, rather than smooth and round. The abnormal blood cells can build up and block blood flow to limbs and organs, causing severe pain and organ damage. The National Heart, Lung, and Blood Institute estimates that up to 100,000 people in the United States, [...]

Successful Outcome Brings Early End To TWITCH Sickle Cell Anemia Clinical Trial

BioNews Texas, by Charles Moore ~ December 1, 2014 Sickle cell anemia is the most common form of sickle cell disease among a group of inherited red blood cell disorders and the most common genetic disease in the U.S., afflicting an estimated 70,000-80,000 Americans according to the William E. Proudford Sickle Cell Fund Inc. Normal red blood cells, which are shaped like doughnuts, contain an iron-rich, oxygen-carrying protein called hemoglobin, and travel easily through the body’s circulatory pathways delivering oxygen to cells. Sickle red blood cells, by contrast, become hard, sticky and shaped like sickles — crescent-shaped hand tools used to cut wheat and other crops prior to the mechanized agriculture era. As these cells hardened, pointed red cells move through small blood passageways, they clog the flow and break apart, causing pain and damage, the risk of infection, and a low blood count, or anemia. Sickle cells also contain abnormal hemoglobin called sickle hemoglobin or hemoglobin S. Sickle hemoglobin is what causes the cells to develop their characteristic crescent shape. Sickle cell disease affects people of many ethnicities, including people whose ancestors were from Mediterranean countries such as Greece, Turkey, and Italy; the Arabian Peninsula; India; and Spanish-speaking regions in South America, Central America, and parts of the Caribbean. However, it disproportionately affects people of African descent. Approximately 1 out of 10-12 African Americans has sickle cell trait — a genetic predisposition to developing sickle cell anaemia, although not all will actually develop the disease. According to a multi-institutional study that included researchers from The University of Texas Health Science Center at Houston (UTHealth), conclusive findings show that hydroxyurea therapy offers safe and effective disease management of sickle cell anemia and reduces the risk [...]

Monthly transfusions reduce strokes in children with sickle cell anemia

Washington University in St. Louis, by Michael C. Purdy ~ August 20, 2014 Monthly blood transfusions reduce the risk of stroke in young patients with sickle cell anemia, scientists report Aug. 20 in The New England Journal of Medicine. An estimated 1 in 3 children with sickle cell anemia experiences silent strokes — loss of blood flow to parts of the brain. Such strokes do not cause immediate symptoms and typically go undiagnosed. But damage from these incidents, which often recur, can lower a child’s IQ. A new multi-institutional study that originated at Washington University School of Medicine in St. Louis showed that giving monthly blood transfusions to sickle cell anemia patients who already had experienced silent strokes reduced by 58 percent their risk of another stroke, silent or otherwise. “The data make transfusion the only evidence-based option to prevent stroke recurrence and further brain injury in this vulnerable population,” said coauthor Michael Noetzel, MD, professor of neurology and of pediatrics and chair of the study’s neurology committee. “Now that we have identified a viable treatment option, early detection of silent cerebral strokes should become a major focus for clinicians and families of children with sickle cell disease.” Noetzel treats patients with strokes from sickle cell anemia at St. Louis Children’s Hospital. He and his colleagues recommend checking children with sickle cell anemia for silent strokes at least once before they start elementary school. If an MRI scan reveals any such strokes, families and physicians should consider monthly blood transfusions. Sickle cell anemia affects about 100,000 people in the United States and occurs most commonly in African-Americans. The disease, inherited from both parents, causes some of the patient’s red blood cells, normally shaped like a [...]