Sickle Cell

SLU Researchers Study Therapy to Relieve Sickle Cell Pain

Newswise, by Staff ~ 1/22/14

Saint Louis University researchers are studying whether ReoPro® (abciximab), a drug currently given to heart patients undergoing angioplasties to open blocked arteries, also could help children and young adults who have severe pain from sickle cell disease.

“Sickle cell crises, which are acute episodes that can land patients in the hospital, can be excruciatingly painful,” said William Ferguson, M.D., director of the division of pediatric hematology and oncology at Saint Louis University and a SLUCare pediatrician at SSM Cardinal Glennon Children’s Medical Center.

“The typical vaso-occlusive crisis puts patients in the hospital for three to five days on intravenous medications. All we can do is give supportive care, such as pain killers, and wait for the crisis to run its course. Our research will tell us if using a medicine like ReoPro could be a valuable strategy in treating a sickle cell crisis.”

Sickle cell crises occur when clots form in the small blood vessels, preventing blood from flowing freely to organs. Healthy red blood cells are shaped like flexible donuts and can fold to easily wiggle through the smallest blood vessels. Red blood cells in patients who have sickle cell disease are misshaped, crescent-like cells with sharp edges that get caught inside blood vessel walls and pile up to create blockages.

Much like an accident that impedes traffic on the road where it happened and on secondary feeder roads, sickle cell crises cause a second blood vessel blockage when red blood cells and platelets (small blood cells that stop bleeding) stick to the lining of the blood vessel walls.

“It’s like there’s a traffic accident and a quarter mile down the road, you slow down again. Right now, we don’t have anything that directly targets that secondary blockage,” Ferguson said. “These traffic pile ups can decrease blood flow and can damage the organ on the other side, such as the spleen, eyes or lungs.”

Ferguson, who is the study chair, said the research could represent a new approach to treating sickle cell crisis. He is leading a study that examines whether or not ReoPro could reduce the length of time patients who are having a sickle cell pain crisis spend in the hospital.

“As far as I know, no one has targeted the increased stickiness of both platelets and red blood cells in the context of a crisis,” Ferguson said. “We hope our research will tell us more about treating the disease and potentially open an avenue of research and drug development.”

Scientists from SLU’s Center for World Health and Medicine reviewed medical literature that identified the mechanism of action used by ReoPro as potentially promising in treating sickle cell crises because it attacks blockages in blood flow on two fronts. They then approached Ferguson about conducting the research, said Peter Ruminski, executive director of the center.

“ReoPro hits both of those proteins that affect the stickiness of platelets and the flow of red blood cells through the walls of the blood vessels. Our research will help us find out if medications that have similar properties can be effective against sickle cell disease,” Ruminski said.

“Sickle cell disease is a neglected disease that dramatically affects members of the St. Louis community who are African American. It is devastating for those who have it in terms of diminished quality of life and shortened lifespan.”

The Center for World Health and Medicine brokered the research project, which is the first clinical trial to come out of its work. While ReoPro has been approved by the Food and Drug Administration to prevent clotting during angioplasty procedures, it has not been studied as a treatment for sickle cell disease. Janssen Biotech, Inc., the company that discovered and developed ReoPro, is donating the medication and providing funding for the study.

Ferguson is recruiting 100 patients who are between ages 5 and 25 for the double-blind randomized trial. Within 16 hours of being hospitalized for a sickle cell pain crisis, half will receive the investigational medicine and half a placebo. All will receive the standard of care, which includes pain medication, while they are in the hospital and released.

Researchers will track how long the volunteers remain in the hospital. Those in the study will be discharged from the hospital once their pain can be controlled by oral medications, provided they have no other medical problems. They will have a follow up visit with their hematologist a week to 10 days after leaving the hospital, which is routine care for those who have suffered a sickle cell crisis.

Sickle cell disease occurs in about one in 400 people of African descent and one in 4,000 Hispanics, affecting between 80,000 and 100,000 Americans. It varies in severity, with some people having significant pain from multiple crises. Typically, those who have sickle cell disease live to be in their 50s.

For some patients, the disease also interferes with the quality of life, Ferguson said.

“If you’re having multiple pain crises and going into the hospital many times a year, it’s hard to go to school or keep a job,” Ferguson said. “In addition, many people have moderate or minor crises in between hospitalizations and take narcotics to relieve the pain. That can compromise a person’s ability to function as well.”

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: infectious disease, liver disease, cancer, heart/lung disease, and aging and brain disorders. The Center for World Health and Medicine is dedicated to developing therapies for rare (orphan) and neglected diseases.

To learn more about the sickle cell disease research at Saint Louis University, call (314) 577-5638.

Studies uncover new insights into pathophysiology of sickle cell disease and thalassemia, may help improve standard of care

Medical News Today, by Staff ~ December 11, 2013

New research presented during the 55th American Society of Hematology Annual Meeting and Exposition in New Orleans uncovers several important insights into the pathophysiology of sickle cell disease and thalassemia that may soon translate into the development of better, more targeted treatments for hundreds of thousands of patients worldwide.

Sickle cell disease (SCD) is an inherited, chronic disorder affecting nearly 100,000 Americans. Instead of producing healthy red blood cells, individuals with the disease produce abnormal hemoglobin, a protein that attaches to oxygen in the lungs and carries it to all parts of the body. This abnormal hemoglobin causes the red blood cells to become rigid and sickle-shaped, which then block blood and oxygen flow to the body and lead to intense pain and infections. Thalassemia, the name for a family of chronic blood disorders characterized by low hemoglobin production, also affects the blood’s ability to transport oxygen and is associated with life-threatening complications.

While there are several ways to treat SCD and thalassemia, these options only manage symptoms and do not correct the underlying genetic defects associated with these disorders. Fortunately, investigators continue to uncover important insights related to the pathophysiology of these blood disorders and their symptoms, fueling the development of new targeted interventions that may lead to improved treatments. Findings presented today explore a promising potential pain management treatment for SCD patients as well as two strategies that use natural proteins to activate the gene responsible for the production of healthy hemoglobin.

“We now know a great deal about the causes of sickle cell disease and thalassemia and how to treat many of the complications; however, new insights and care strategies that can allow for better management of these diseases are desperately needed,” said John Tisdale, MD, moderator of the press conference and Senior Investigator of the Molecular, Clinical, and Hematology branch at the National Heart, Lung, and Blood Institute at the National Institutes of Health in Bethesda, Md. “Exciting new developments being reported today include a new therapy that could help sickle cell patients better manage pain crises and two new gene therapy strategies that could allow patients with both sickle cell disease and thalassemia to produce healthy hemoglobin. These advances bring us one step closer to achieving our goal of improving the long-term outlook and enhancing the quality of life of patients with these serious disorders.”

GMI 1070: Reduction in Time to Resolution of Vaso-Occlusive Crisis and Decreased Opioid Use in a Prospective, Randomized, Multi-Center Double Blind, Adaptive Phase II Study in Sickle Cell Disease [776]

Vaso-occlusive crisis (VOC) is a common and painful complication of sickle cell disease (SCD) that occurs when sickled red blood cells and white blood cells stick to the lining of blood vessels, blocking blood flow and preventing oxygen from reaching parts of the body. Sickle cell patients experiencing VOC typically receive potent drugs to alleviate intense pain, but these medications only manage the symptoms and do not attack the root cause of the crisis. Previous research has suggested that molecules called selectins involved in cell-to-cell adhesion may be a significant driver of VOC. Recent studies of a new selectin inhibitor compound GM 1070 in animals have demonstrated efficacy in reducing VOC in that model system.

Newly Discovered Gene Regulator Could Precisely Target Sickle Cell Disease

Regenerative Medicine, by Staff ~ November 11, 2013

“Coupled with recent advances in technologies for gene engineering in intact cells, it could lead to powerful ways of manipulating hemoglobin production and new treatment options for hemoglobin diseases.” –Dr. Stuart Orkin.

A research team from Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and other institutions has discovered a new genetic target for potential therapy of sickle cell disease (SCD). The target, called an enhancer, controls a molecular switch in red blood cells called BCL11A that, in turn, regulates hemoglobin production.

The researchers — led by Daniel Bauer, MD, PhD, and Stuart Orkin, MD, of Dana-Farber/Boston Children’s — reported their findings recently.

Prior work by Orkin and others has shown that when flipped off, BCL11A causes red blood cells to produce fetal hemoglobin that, in SCD patients, is unaffected by the sickle cell mutation and counteracts the deleterious effects of sickle hemoglobin. BCL11A is thus an attractive target for treating SCD.

The disease affects roughly 90,000 to 100,000 people in the United States and millions worldwide.

However, BCL11A plays important roles in other cell types, including the immune system’s antibody-producing B cells, which raises concerns that targeting it directly in sickle cell patients could have unwanted consequences.

The discovery of this enhancer — which regulates BCL11A only in red blood cells — opens the door to targeting BCL11A in a more precise manner. Approaches that disable the enhancer would have the same end result of turning on fetal hemoglobin in red blood cells due to loss of BCL11A, but without off-target effects in other cell types.

The findings were spurred by the observation that some patients with SCD spontaneously produce higher levels of fetal hemoglobin and enjoy an improved prognosis. The researchers found that these individuals possess naturally occurring beneficial mutations that function to weaken the enhancer, turning BCL11A’s activity down and allowing red blood cells to manufacture some fetal hemoglobin.

“This finding gives us a very specific target for sickle cell disease therapies,” said Orkin, a leader of Dana-Farber/Boston Children’s who serves as chairman of pediatric oncology at Dana-Farber Cancer Institute and associate chief of hematology/oncology at Boston Children’s Hospital. “Coupled with recent advances in technologies for gene engineering in intact cells, it could lead to powerful ways of manipulating hemoglobin production and new treatment options for hemoglobin diseases.”

“This is a very exciting study,” said Feng Zhang, PhD, a molecular biologist and specialist in genome engineering at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology (MIT) and the Broad Institute of MIT and Harvard, who was not involved in the study. “The findings suggest a potential new approach to treating sickle cell disease and related diseases, one that relies on nucleases to remove this regulatory region, rather than adding an exogenous gene as in classic gene therapy.”

UCLA Stem Cell Therapy for Sickle Cell Disease Advances Toward Clinical Trials

Newswise, by Staff ~ July 1, 2013

Researchers at UCLA’s Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research have successfully established the foundation for using hematopoietic (blood-producing) stem cells (HSC) from the bone marrow of patients with sickle cell disease (SCD) to treat the disease. The study was led by Dr. Donald Kohn, professor of pediatrics and microbiology, immunology and molecular genetics in the life sciences.

Kohn introduced an anti-sickling gene into the HSC to capitalize on the self-renewing potential of stem cells and create a continual source of healthy red blood cells that do not sickle. The breakthrough gene therapy technique for sickle cell disease is scheduled to begin clinical trials by early 2014. The study was published online ahead of press today in Journal of Clinical Investigation.

Gene Therapy

Kohn’s gene therapy approach using HSC from patient’s own blood is a revolutionary alternative to current SCD treatments as it creates a self-renewing normal blood cell by inserting a gene that has anti-sickling properties into HSC. This approach also does not rely on the identification of a matched donor, thus avoiding the risk of rejection of donor cells. The anti-sickling HSC will be transplanted back into the patient’s bone marrow and multiplies the corrected cells that make red blood cells without sickling.

“The results demonstrate that our technique of lentiviral transduction is capable of efficient transfer and consistent expression of an effective anti-sickling beta-globin gene in human SCD bone marrow progenitor cells, which improved the physiologic parameters of the resulting red blood cells.” Kohn said.

Kohn and colleagues found that in the laboratory the HSC produced new non-sickled blood cells at a rate sufficient for significant clinical improvement for patients. The new blood cells survive longer than sickled cells, which could also improve treatment outcomes. The success of this technique will allow Kohn to begin clinical trials in patients with SCD by early next year.

Sickle Cell Disease

Affecting more than 90,000 patients in the US, SCD mostly affects people of Sub-Saharan African descent. It is caused by an inherited mutation in the beta-globin gene that makes red blood cells change from their normal shape, which is round and pliable (like a plastic bag filled with corn oil), into a rigid sickle-shaped cell (like a corn flake). Normal red blood cells are able to pass easily through the tiniest blood vessels, called capillaries, carrying oxygen to organs such as the lungs, liver and kidneys. But due to their rigid structure, sickled blood cells get stuck in the capillaries and deprive the organs of oxygen, which causes organ dysfunction and failure.

Current treatments include transplanting patients with donor HSC, which is a potential cure for SCD, but due to the serious risks of rejection, only a small number of patients have undergone this procedure and it is usually restricted to children with severe symptoms.

CIRM Disease Team Program

This study was supported in part by a Disease Team I Award from the California Institute for Regenerative Medicine (CIRM), the state’s stem cell research agency created by voter initiative in 2004. The purpose of the disease team program is to support research focused on one particular disease that leads to the filing of an investigational new drug application with the FDA within four years. The program is designed to encourage translational research, which means to take scientific discoveries from the laboratory to the patient bedside as quickly as possible. This requires new levels of collaboration between basic laboratory scientists, medical clinicians, biotechnology experts and pharmacology experts, to name a few.

Other support came from the UCLA Broad Stem Cell Research Center and Jonsson Comprehensive Cancer Center and the Ruth L. Kirschstein National Research Service Award.

The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA’s Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at

Sickle cell drug begins Phase 2 trials

U~T San Diego, by Bradley J. Fikes ~ June 16, 2013

A new approach to reducing sickle cell anemia’s painful attacks has entered Phase II clinical trials.

The drug, Lexiscan, is already approved for diagnosing heart disease. Scientists led by Joel Linden, a researcher at the La Jolla Institute for Allergy & Immunology, discovered that the drug might also be useful for relieving the attacks sickle cell patients periodically suffer.
photoNormal red blood cells take a circular shape, while sickle cells take bent, angular shapes that cause them to clump in capillaries, cutting off the flow of blood to tissues. — Betty Pace
Patients are now being recruited for the Lexiscan study, to be conducted in Boston, Baltimore, Detroit, Chicago, Cincinnati, Milwaukee, Chapel Hill, and St. Louis. Dana-Farber Cancer Institute in Boston is the sponsor; the La Jolla Institute is a collaborator. Linden is the study’s co-lead investigator with David G. Nathan, of Dana-Farber (the “dean of hematology,” Linden calls him) and Joshua Field of BloodCenter of Wisconsin.

The trial is funded by a $10.8 million grant from the National Institutes of Health.

Lexiscan has an anti-inflammatory effect, and the trial is to study whether the drug can reduce inflammation and pain during an attack, helping restore blood flow. Research has suggested that sickle cell anemia is not merely the result of deformed red blood cells; inflammation is also involved.

A molecular disease

Separately, San Diego-based HemaQuest said it has finished recruiting sickle-cell patients for a Phase 2b trial of its drug, HQK-1001. That drug, HQK-1001, induces production of fetal hemoglobin, which appears to compensate for the abnormal hemoglobin in sickle cell anemia. It has received orphan drug designation for both sickle cell disease and beta thalassemia in both the United States and Europe.

HemaQuest moved its headquarters from Seattle to San Diego in 2011. It was founded in 2007 in Newton, Mass.

Sickle cell disease is caused by a mutation in hemoglobin, the oxygen-carrying protein in red blood cells. It makes the cells curve in a characteristic sharply curved shape, instead of the normal doughnut shape. The angular lines of these cells cause them to clump in capillaries, cutting off the flow of blood, called ischemia, and starting a cascade of damage.

The disease mainly occurs in people with ancestry from certain parts of sub-Saharan Africa and the Middle East where malaria has been endemic. Those who carry one gene for the mutant hemoglobin are healthy and partially protected from malaria, but those with two genes get the disease. In the United States, the disease is most common in African-Americans.

There are various types of sickle cell disease, some occurring in conjunction with another harmful mutation that causes beta thalassemia. The sickle cell mutation was reported in the November, 1949 issue of Science by researchers including Linus Pauling. It was the first description of a molecular disease.

Linden has studied the ischemic process for years; he specializes in the effects of adenosine, a breakdown element of ATP whose levels are increased by ischemia. (San Diego history note: Gensia, a company once based in San Diego, unsuccessfully tested adenosine-regulating drugs for cardiac uses. It moved to Irvine, changed its name to Gensia Sicor and entered the generics business. The company was later purchased by Israeli pharmaceutical company Teva.)
Heart attack is ischemia in the coronary arteries. It is often treated by installing stents to restore blood flow. But damage can continue even then, Linden said.

“During the period of tissue ischemia, some of those tissues have been damaged,” Linden said. “They’re hypoxic, they’re not getting any nutrients, and when blood starts flowing into those little blood vessels, the white cells become adherent and they literally clog up the microvessels. So you go initially from a vessel that’s clogged with atherosclerosis or a clot, you open that up, and you end up with a secondary clogging. Except now, it’s in the tiny blood vessels that are downstream.”

Cardiologists call this the “no reflow” phenomenon Linden said.

“They’ll balloon open an artery, blood will start to flow, and then it will stop again,” Linden said.

Linden and colleagues studying no-reflow found that drugs activating adenosine receptors on the NKT white blood cells turned off their adherent effect, and could block the reperfusion injury.

“We found that there was an inflammatory cascade initiated by the activation of these cells and then you ended up activating a whole bunch of white cells, including neutrophils, which are abundant, and these would actually clog up the arterioles and venules,” Linden said.

Sickle cell connection

Linden says he made the link between reperfusion injury and sickle cell anemia while reading a journal about the disease.

“There are two things I read: One is that sickle-cell anemia is associated with vaso-occusion, multi-tissue, widely disseminated. The other thing is that patients who have this disease have white-cell activation,” Linden said. “So I thought, geez, this sounds just like ischemia reperfusion injury, in fact it probably is ischemia reperfusion injury. These red cells are basically creating vaso-occlusion, just like you have in coronary artery disease, except that instead of it being caused by a lipid plaque or a clot, it’s caused by red cells that are occluding the micro-vasculature.”

Linden and colleagues experimented on transgenic mice that had been given the mutated human hemoglobin gene, causing the mice to make sickle-shaped red blood cells. The mice were then treated to remove the white blood cells that cause the inflammation. They got much better, although still ill, Linden said.

“What we figured out we were doing is we were blocking the white cell activation,” he said. And that led to a different view of sickle-cell anemia than the classic model.

“Instead of thinking of sickle cell anemia just as a disease of red cells, the new concept was, it’s a combination of red cells and white cells,” Linden said. “Red cells cause the initial injury, then you get ischemia, and then you generate factors that activate these NKT cells and other white cells, and you get a multi-cellular aggregate that clogs up the arteries.”

This change in thinking was exemplified by an Aug. 1, 2000 article in the Journal of Clinical Investigation reporting that reperfusion injury occurred in the transgenic sickle cell mice but not in normal mice. Linden and colleagues then found the mechanism that caused the NKT cells to start the process.

A company called NKT Therapeutics is conducting a Phase I clinical trial of a monoclonal antibody that depletes the NKT cells in patients with stable sickle cell disease.

“The hope is they’ll get long-term protection without getting too much immunosuppression,” Linden said.

Temporary halt

However, Linden said it’s better not to deplete white blood cells, to preserve their infection-fighting power. His group’s approach is to temporarily turn off the cells’ ability to aggregate, by administering a drug during a crisis.

“It turns out adenosine receptors on these T cells turn them off,” Linden said. “So we thought all we need to do is treat with adenosine, or synthetic adenosine analogs that activate this particular receptor, and that’s going to turn off these cells.”

Linden and colleagues then looked for such adenosine analogs. They found one in Lexiscan, which was already approved for pharmacological stress-testing for heart disease. Lexiscan opens up coronary arteries, similar to what exercise would do. It’s given for patients who aren’t able to safely exercise for a stress test.

Lexiscan is injected rapidly for stress-testing; for sickle cell patients it is given as an infusion of up to 48 hours. The safety of this approach was successfully tested in a Phase I study. Linden’s role is to analyze the white cells for activation.

“As a secondary endpoint, we took blood from these patients and looked at the NKT cell activation markers,” Linden said. “We found out that in sickle cell disease they were really activated, which is exactly what we saw in the mice. And when we gave them the adenosine compound the activation was inhibited.”

Asked why there were no trial sites in California, Linden said part of the issue is finding sites that not only have large numbers of sickle cell patients, but also research programs suited to the study.

Bone marrow transplants offer cure for sickle cell patients

Sunday, July 8, 2012

By: Sandra Jordan

Little Gabby Carter of Cape Girardeau, Missouri thought going to the hospital all the time, frequent bouts of pain, staying inside during temperature extremes and fatigue were just a normal part of life. That is, until she started kindergarten.”Kindergarteners have a lot of recesses and they do a lot of things that she couldn’t do,” Debbie Carter, Gabby’s mother, said. “She got tired a lot with the activities that they do; she just couldn’t keep up and so she’d have to take frequent naps.”Gabby is one of the patients at St. Louis Children’s Hospital with sickle cell disease who are or will become stem cell or the bone marrow transplant recipients this summer.

“We have three that are in right now; we have one that has already had her transplant and is in the early phase of recovery,” Dr. Monica Hulbert, director of the Sickle Cell Disease Program at St. Louis Children’s Hospital and assistant professor of pediatrics Washington University St. Louis.

Sickle cell disease is an inherited blood disorder affecting millions of people of color around the globe. Varying types of sickle cell diseases are commonly found among African, Indian, Mediterranean, Middle-eastern, Caribbean and Latin populations.

With sickle cell disease, red blood cells produce abnormal hemoglobin, a protein that carries oxygen throughout the body and takes carbon dioxide to the lungs to breathe out. Normally rounded red blood cells are crescent or sickle shaped, reducing their ability to transport oxygen throughout the body. The sickled cells can group together and clog pathways in the bloodstream, causing painful attacks, known as episodes or crises. The disease can damage vital organs and cause strokes and premature death.

In Missouri, it is estimated one in 400 African Americans have the disease and one in 12 have the sickle cell trait, which can be passed to their children.  If both parents have the sickle cell trait, there is a one in four chance their child will also have sickle cell anemia.

Hulbert’s colleague, Dr. Shalini Shenoy, associate director of the bone marrow transplant program, has developed and is chair of several national studies to figure out ways to make bone marrow transplants available for more patients and with less side effects.

“It’s really a great opportunity to kind of see that unfold and we have multiple patients coming into the transplant unit this summer for hopefully what will be curative treatment for their sickle cell disease,” Hulbert said.

As exciting as that is for the patients, their families and their health care team, many other children need a bone marrow match.

“We have 15 or 20 kids that are waiting with no donors,” Hulbert said.

To become a bone marrow donor, persons need to sign up through to get tested.

“To register to be a donor it requires just having a condensed swab of your cheek and filling out a bunch of forms and you could be called at any time if there was somebody who matched you – to be willing to donate for any person that you may not know, and you won’t know, most likely,” Hulbert said.

People are more likely to match somebody who is more genetically like them, making it more difficult to find acceptable matches for African Americans and any person of color, she said.

“There are not as many people of color signed up to be donors,” Hulbert said. “And that’s true not just for sickle cell disease but for other diseases that can affect anybody – like leukemia, aplastic anemia or bone marrow failure. We really need people to register to be donors for any patient that may need a bone marrow transplant.”

The hospital is also working with the St. Louis Cord Blood Bank to try and identify ways to improve cord blood donations from women of color after their babies are born.

“The cord blood contains a lot of the elements we need that are called stem cells, which can actually kind of repopulate somebody’s bone marrow and those can be what we call an alternative source instead of a bone marrow donor,” Hulbert said.  “Cord blood can be for somebody to have a transplant for sickle cell or any other similar blood disease.”

After going on the bone marrow transplant list in March 2011, two matching bone marrow donors did not work out – one because of medical reasons and the other donor just backed out. Gabby’s mother said she didn’t have time to become angry or bitter. The medical team pursued and found another option – a cord blood match for a stem cell transplant.

Gabby underwent two rounds of chemotherapy at Children’s before having a cord blood stem cell transplant on July 3.

The National Institutes of Health researchers have also reported successful results in the U.S. with stem cell transplants to adult sickle cell patients, although risks for rejection are higher with age and after experiencing major sickle cell complications.

Children’s will have an informational booth at the upcoming Sickle Cell Stroll, which takes place Saturday, July 28 at 9 a.m. in the Upper Muny Parking Lot in Forest Park in St. Louis. To register or for more information, call 314-277-3950, or visit

Chicago Woman Cured of Sickle Cell Disease

Tuesday, June 19, 2012

By: University of Illinois at Chicago

ScienceDaily (June 18, 2012) — Chicagoan Ieshea Thomas is the first Midwest patient to receive a successful stem cell transplant to cure her sickle cell disease without chemotherapy in preparation for the transplant. University of Illinois Hospital & Health Sciences System physicians performed the procedure using medication to suppress her immune system and one small dose of total body radiation right before the transplant.

The transplant technique is relatively uncommon and is a much more tolerable treatment for patients with aggressive sickle cell disease who often have underlying organ disease and other complications, says Dr. Damiano Rondelli, professor of medicine at UIC, who performed Thomas’s transplant.

The procedure initially allows a patient’s own bone marrow to coexist with that of the donor. Since the patient’s bone marrow is not completely destroyed by chemotherapy or radiation prior to transplant, part of the immune defense survives, lessening the risk of infection. The goal is for the transplanted stem cells to gradually take over the bone marrow’s role to produce red blood cells — normal, healthy ones.

Thomas, 33, had her first sickle cell crisis when she was just 8 months old. Her disease became progressively worse as an adult, particularly after the birth of her daughter. She has spent most of her adult life in and out of hospitals with severe pain and has relied on repeated red blood cell transfusions. Her sickle cell disease also caused bone damage requiring two hip replacements.

“I just want to be at home with my daughter every day and every night,” said Thomas, who depends on family to help care for her daughter during her frequent hospitalizations.

This type of stem cell transplant is only possible for patients who have a healthy sibling who is a compatible donor.

Thomas’ sister was a match and agreed to donate blood stem cells through a process called leukapheresis. Several days prior to leukapheresis, Thomas’ sister was given drugs to increase the number of stem cells released into the bloodstream. Her blood was then processed through a machine that collects white cells, including stem cells. The stem cells were frozen until the transplant.

Last Nov. 23, four bags of frozen stem cells were delivered to the hospital’s blood and marrow transplant unit. One by one, the bags were thawed and hung on an IV pole for infusion into Thomas. The procedure took approximately one hour. Her 13-year-old daughter, Miayatha, was at her bedside.

Six months after the transplant, Thomas is cured of sickle cell disease and no longer requires blood transfusions.

“The donor cells have taken over completely, and blood tests show no sickle cell disease,” said Rondelli, director of the blood and marrow transplant program at UI Hospital. Thomas continues to take medication to prevent rejection of the donor stem cells.

About 25 adults have received a similar chemotherapy-free stem cell transplant for sickle cell disease in recent years at the National Institutes of Health in Bethesda, Md. Approximately 85 percent have been cured.

“Sickle cell disease is devastating — both emotionally and physically,” said Dr. Dennis Levinson, a private rheumatologist in Chicago and clinical associate professor of medicine at UIC, who has taken care of Thomas for the past 16 years. “I’ve been terribly frustrated with Ieshea’s disease over the years, and I’ve cared for many other sickle cell patients who have died.”

Levinson says the stem cell transplant provides new hope for patients who often live day-to-day on painkillers and who are often misunderstood by clinicians. As the former chief of medicine at the now closed Michael Reese Hospital, he said he has cared for many patients with sickle cell anemia and was determined to seek out the best treatment option for Thomas.

Sickle cell disease primarily affects people of African descent. It is an inherited defect of the red blood cells that causes them to be shaped like a crescent, or sickle. These abnormal cells deliver less oxygen to the body’s tissues and can result in severe pain, stroke and organ damage.

Approximately one in every 500 African Americans born in the U.S. has sickle cell disease. The disease affects 80,000 Americans of different ethnic backgrounds.

UAB researcher Townes receives Hudson Alph prize

Tuesday, May 22, 2012

By: Lee Roop

Dr. Tim Townes of the University of Alabama in Birmingham has been awarded the $20,000 HudsonAlpha Prize for his work on sickle cell and related blood disorders.

HUNTSVILLE, Alabama — Dr. Tim Townes of the University of Alabama in Birmingham has been awarded the $20,000 HudsonAlpha Prize for his work on sickle cell and related blood disorders.

The award was announced Thursday at the spring benefit of the HudsonAlpha Institute for Biotechnology in Huntsville. “In research you never speak lightly of curing a disease, but if anyone is going to cure sickle cell, it will be Tim,” said Dr. Rick Myers, director and president of HudsonAlpha.

Townes, professor and chairman of the Department of Biochemistry and Molecular Biology at UAB, studies molecular genetics in red blood cells. Using mice, he and colleagues have been able to “reprogram cells that mimic sickle cell anemia as induced pluripotent stem cells,” a HudsonAlpha release said. Those cells have the potential of becoming any type of tissue. Researchers have corrected the DNA mutation associated with sickle cell, placed the cells back into donor mice and produced healthy red blood cells. He has repeated similar steps in humans up to replacing the corrected cells.

Correcting Sickle Cell Disease with Stem Cells

Wednesday, September 28, 2011

By: Johns Hopkins Medicine

Using a patient’s own stem cells, researchers at Johns Hopkins have corrected the genetic alteration that causes sickle cell disease (SCD), a painful, disabling inherited blood disorder that affects mostly African-Americans. The corrected stem cells were coaxed into immature red blood cells in a test tube that then turned on a normal version of the gene.

The research team cautions that the work, done only in the laboratory, is years away from clinical use in patients, but should provide tools for developing gene therapies for SCD and a variety of other blood disorders.

In an article published online August 31 in Blood, the researchers say they are one step closer to developing a feasible cure or long-term treatment option for patients with SCD, which is caused by a single DNA letter change in the gene for adult hemoglobin, the principle protein in red blood cells needed to carry oxygen. People who inherited two copies — one from each parent — of the genetic alteration, the red blood cells are sickle-shaped, rather than round. The misshapen red blood cells clog blood vessels, leading to pain, fatigue, infections, organ damage and premature death.

Although there are drugs and painkillers that control SCD symptoms, the only known cure — achieved rarely — has been bone marrow transplant. But because the vast majority of SCD patients are African-American and few African-Americans have registered in the bone marrow registry, it has been difficult to find compatible donors, says Linzhao Cheng, Ph.D., a professor of medicine and associate director for basic research in the Division of Hematology and also a member of the Johns Hopkins Institute for Cell Engineering. “We’re now one step closer to developing a combination cell and gene therapy method that will allow us to use patients’ own cells to treat them.”

Using one adult patient at The Johns Hopkins Hospital as their first case, the researchers first isolated the patient’s bone marrow cells. After generating induced pluripotent stem (iPS) cells — adult cells that have been reprogrammed to behave like embryonic stem cells — from the bone marrow cells, they put one normal copy of the hemoglobin gene in place of the defective one using genetic engineering techniques.

The researchers sequenced the DNA from 300 different samples of iPS cells to identify those that contained correct copies of the hemoglobin gene and found four. Three of these iPS cell lines didn’t pass muster in subsequent tests.

“The beauty of iPS cells is that we can grow a lot of them and then coax them into becoming cells of any kind, including red blood cells,” Cheng said.

In their process, his team converted the corrected iPS cells into immature red blood cells by giving them growth factors. Further testing showed that the normal hemoglobin gene was turned on properly in these cells, although at less than half of normal levels. “We think these immature red blood cells still behave like embryonic cells and as a result are unable to turn on high enough levels of the adult hemoglobin gene,” explains Cheng. “We next have to learn how to properly convert these cells into mature red blood cells.”

Only one drug treatment has been approved by the FDA for treatment of SCD, hydroxyurea, whose use was pioneered by George Dover, M.D., the chief of pediatrics at the Johns Hopkins Children’s Center. Outside of bone marrow transplants, frequent blood transfusions and narcotics can control acute episodes.

The research was funded by grants from the Maryland Stem Cell Fund and the National Institutes of Health, and a fellowship from the Siebel Foundation.

Authors on the paper are Jizhong Zou, Xiaosong Huang, Sarah Dowey, Prashant Mali and Cheng, all from The Johns Hopkins University.

Patient Hopes Experimental Bone Marrow Transplant Will Cure Her of Sickle Cell Disease

Sunday, May 23, 2010

By: Shavonne Potts Salisbury (N.C.) Post

More than 80,000 U.S. residents, mainly people of African ancestry, are affected by the inherited blood disorder.

Kelly Holloway reaches out for her cat, Jax, a rescued Persian with long cream-colored fur, but she’s not quite able to connect with him.

It could be the mask, gloves or the hospital gown she wears over her clothes. Holloway is almost completely covered from head-to-toe. It’s the best way to protect herself and her immune system.

Holloway, who grew up in Cleveland, recently underwent a procedure that she hopes will completely cure her of the inherited blood disorder, sickle cell disease.

At 6 months old, Holloway was diagnosed with sickle cell, which causes red blood cells to contort and causes them to block blood vessels.

“Her blood count was low and the doctors did another test,” said Alice Holloway, Kelly’s mother.

That second test confirmed doctors’ suspicions that the infant had sickle cell.

Sickle cell is caused by abnormal hemoglobin, a protein in red blood cells that transports oxygen and gives blood its red color. Normal red blood cells look like doughnuts without holes and move easily through the blood vessels. Sickle cells form a “C” or sickle shape and clump in the blood vessels.

In the United States, more than 80,000 people are affected by sickle cell disease, mainly people of African ancestry and to a lesser extent people of Hispanic, Middle Eastern, Asian and white ancestry.

Kelly, now in her 40s, is a part of a study at the National Institutes of Health in Bethesda, Md., where she’s received an experimental bone marrow transplant that researchers believe is a possible cure for sickle cell disease.

Living with sickle cell

As a child, Kelly’s blood count was constantly monitored because sickle cells break up easily and survive for only 10 to 20 days. Normal red blood cells survive 120 days, which can make blood transfusions pretty routine. Transfusions increase the number of normal red blood cells in the body.

Kelly was given penicillin frequently since sickle cell disease makes it harder to fight infections because of decreased immune function.

“They put so much penicillin in her she became allergic,” Alice said.

Kelly could have a common cold one day, bronchitis the next and eventually double pneumonia. She had several bouts of pneumonia as a child. She also had to stay hydrated since blood can thicken and cause blockages in blood vessels when it’s dehydrated.

Although Kelly has been affected with the disease her entire life, she’s still led a pretty normal existence. She graduated from West Rowan High and went on to graduate from Livingstone in 1996 with degrees in sociology and business. She has modeled and appeared on the cover of magazines.

Awaiting a kidney

When cells become hard and pointed like the sickle they’re named for, they often get stuck and block the vessels. This blockage can lead to pain, stroke and damage to major organs. Kelly now needs a kidney transplant.

In the meantime, she has daily kidney dialysis, and without this, toxic wastes build up in her blood and tissues. She also has gallstones, injections in her left eye to stop bleeding and pulmonary arterial hypertension (which is high blood pressure in the lung arteries that make it harder for blood to flow through).

A new treatment

During a visit with her cardiologist, Kelly was referred to the National Institutes of Health, where researchers were doing a study on pulmonary hypertension. Kelly went through a week of testing.

“I told them, ‘I think I need a stem cell transplant,’ ” she said, sort of joking.

But her casual comment was taken seriously and she was enrolled in a modified blood adult stem-cell transplant regimen study.

Bone marrow transplants have been used to treat sickle cell disease for 20 years, but almost all of the 200 cured have been children.

The process began with Kelly’s sister, Nieda, who had a procedure that stimulates the bone marrow to produce stem cells. The stem cells are collected and the rest of the cells are infused back into the body.

“They were hoping to get 5,000 cells and they got 15,000,” Alice said.

The “new” red blood cells from the donor allows the healthy cells to outlast and replace the disease-causing cells.

“The bone marrow transplant is the only cure that can be offered to treat sickle cell where traditionally a brother or sister is a match,” said Dr. Courtney Fitzhugh.

Fitzhugh co-authored a paper about full-matched stem cell transplantation in sickle cell disease, which appeared in the December 2009 edition of the New England Journal of Medicine. She’s written a protocol for a half-matched person who can serve as a donor. It took the better part of six months to write the protocol for this study.

Johns Hopkins University has conducted similar research, but Kelly is the first and only half-matched recipient at the National Institutes of Health.

Repeated attempts to contact researchers at Johns Hopkins University’s Sickle Cell Center for Adults were unsuccessful.

The decision to become the first half-matched recipient wasn’t a hard one, Kelly said.

“It was all worth it. I would do it again,” she said.

The trial was conducted in Maryland by National Institutes of Health researchers at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases.

A sibling is usually the best match because it ensures the patient’s body does not reject the new marrow. In other studies, stem cells donated from parents often are rejected in their new environment.

In Kelly’s case, her younger sister was the half match she needed. Currently, 72 percent of Nieda’s blood cells have taken over Kelly’s blood.

“We can tell what percentage of those cells come from the donor. We’ve found that we don’t have to completely replace the recipient’s cells,” Fitzhugh said.

Levels as much as 10 percent could reverse sickle cell disease, she said.

“A parent should be a half match to a child and every sibling has a 50 percent chance of being a half match, a 25 percent chance of being a full match and 25 percent chance of not being a match at all,” Fitzhugh said.

The patient’s body can reject the cells and the sickle cell can return. What researchers do is give the patient medication and radiation to prevent rejection.

A week before the procedure, Kelly was given low-dose chemotherapy and full-body radiation. After Kelly received a treatment, she had an unexpected side effect that left her hair matted. Her hair was so fused together she had to cut it.

Most participants who were full-matched were completely bald, Kelly said.

She’s been in isolation for the last month and was released May 4.

In the December study, nine of 10 adults who received full matched stem cell transplants had effective reversal of sickle cell disease.

“We should start to get some idea around three to six months if it (half-matched) worked for Kelly,” Fitzhugh said.

Now Kelly must wait. She has faith that this procedure will be a definite cure.

“I have to have faith. That’s what all the prayers are for — a cure,” she said.

Her mother hopes this will be the answer to many others’ prayers.

“There is a cure for sickle cell and people don’t have to suffer,” Alice said.

“It’s important for people to be aware of sickle cell and know that bone marrow is an option. We are really trying to help improve the lives of patients,” Fitzhugh said.

It will be years before the treatment is applied on a larger scale, she said.

Health care providers and sickle cell patients, or their family members, who may be interested in joining the study should call 301-402-6466 for more information.