Medical leap gives hope to blood disorder sufferers

January 16, 2011

Gene therapy for the blood disorder beta-thalassemia will be carried out in Thailand for the first time by the end of this year.

A team of doctors at Ramathibodi Hospital is studying the gene therapy technology alongside experts in Paris under a collaboration programme between the Mahidol University led by Prof Suthat Fucharoen and French-American researcher Philippe Leboulch of Harvard Medical School and the University of Paris.

The Thai doctors expect to return to Thailand to conduct a trial around December, said Dr Suradej Hongeng, of Ramathibodi Hospital’s department of pediatrics.

The collaboration came about after the world’s first successful treatment of beta-thalassemia with gene therapy.

A 21-year-old Frenchman treated with the therapy in 2007 now no longer has the need for blood transfusions. He previously had required transfusions every month since birth.

The successful treatment was published in the journal Nature last September.

Beta-thalassemia is caused when a patient cannot produce enough of the beta-globin component of haemoglobin, the protein used by red blood cells to carry oxygen around the body. This can cause life-threatening anaemia, leading to severe damage of the body’s major organs.

Gene therapy is generally the insertion, alteration or removal of genes within a patient’s cells and biological tissues to treat disease.

“This success justifies the hopes placed in the use of gene therapy to treat blood diseases,” said Dr Suradej, a haematology specialist.

“It is also the first time an effective technology has been developed to improve the quality of life for people with thalassemia.”

An estimated 20 million Thais are carriers of thalassemia. It is one of the world’s most common genetic disorders, putting an enormous financial strain on Thailand and countries located in the “Thalassemia Belt”, which stretches from the Mediterranean through the Middle East and Central Asia to Southeast Asia.

About three in 800 children born in Thailand are affected by the severest form of the disorder, beta-thalassemia, requiring regular blood transfusions.

However, blood transfusions carry the risk of contracting HIV and hepatitis B and C from donors, or iron overloading.

The only known cure for the condition is through a bone marrow transplant.

However, this process is dangerous and it can be very difficult to find a matching bone marrow donor, Dr Suradej said.

He hoped the gene therapy for thalassemia treatment would eliminate the problems posed by bone marrow transplants, as well as lead doctors to adapt the technology to treat the symptoms of beta-thalassemia, such as as neurological problems and muscle disabilities.

NATURE Publishes Promising Results on Treatment of First Patient in bluebird bio’s Phase 1/2 Beta-Thalassemia Study

September 24, 2010
bluebird bio (formerly Genetix Pharmaceuticals Inc.) an emerging leader in the development of innovative gene therapies for severe genetic disorders, today announced publication in the journal Nature of its promising Phase 1/2 data highlighting positive results of LentiGlobin™ gene therapy treatment in a young adult with severe beta-thalassemia, a blood disorder that is one of the most frequent inherited diseases.
The patient, who had been transfusion dependent since early childhood, has become transfusion independent for the past 21 months – more than two years after treatment with the LentiGlobin vector. The study also identified a subset of cells with the corrected beta-globin gene that overexpressed a truncated form of a gene called HMGA2. The patient has not experienced any adverse events. The data show that while early on, the HMGA2 clone was a significant portion of the corrected cells, the clone levels had declined at the time the paper was prepared, and further follow up indicates the decline is continuing.
“Although based on the first treated patient, we believe these results are impressive and illustrate for the first time the significant potential for treatment of beta hemoglobinopathies using lentiviral beta-globin gene transfer in the context of autologous stem cell transplant,” said Philippe Leboulch, M.D., senior author of the study and head of the Institute of Emerging Diseases and Innovative Therapies of CEA and INSERM; professor of medicine, University of Paris; and visiting professor, Harvard Medical School. “For beta-thalassemia, we have worked intensely for almost 20 years to design, develop and manufacture LentiGlobin to provide a sustained high level hemoglobin production, resulting in a major clinical benefit. It has been very rewarding to follow this patient as his life has dramatically improved since receiving our treatment.”
“For the first time, a patient with severe beta-thalassemia is living without the need for transfusions over a sustained period of time,” said Marina Cavazzana-Calvo, M.D., first co-author of the study and professor of hematology, University of Paris and chief of Cell and Gene Therapy Department, Necker-Enfants Malades Hospital in Paris. Salima Hacein-Bey-Abina, Ph.D., professor of immunology, University of Paris, added, “These results are not only important due to the tremendous medical need that exists for thalassemia patients around the world, but also represents a significant step forward for the field of autologous stem cell therapy as an emerging therapeutic modality.”
Dr. Françoise Bernaudin, the clinical hematologist who has followed this patient since early childhood, said, “It is wonderful to see that this young man is for now free of transfusions and injections for iron chelation. He is happy to have a normal life back, and for the first time has a full-time job as a cook in a main restaurant in Paris. We are now even able to bleed him regularly to help remove toxic iron that had accumulated over the years because of blood transfusions.”
The paper, titled “Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassemia,” is available in the online publication of Nature at
“We believe the human findings in beta-thalassemia, as well as the recently published data in Science on two patients with childhood cerebral adrenoleukodystrophy (CCALD), highlight the significant opportunity for bluebird bio’s gene therapy platform to help patients with severe genetic disorders,” said Nick Leschly, president and CEO of bluebird bio. “We are committed to building a world-class company in gene therapy led by outstanding people as we move aggressively forward with multiple clinical studies, including our ongoing clinical trials for the development of LentiGlobin for beta-thalassemia and our product for CCALD.”

Cryo Cell Pakistan

August 10, 2010

Thalassemia is the most common inherited single gene disorder in the world. The thalassemias are a diverse group of genetic blood diseases characterized by absent or decreased production of normal hemoglobin, resulting in a microcytic anemia of varying degree.

Your blood count may be a little lower than other people of your age and sex, but this produces no symptoms. You were born with this condition and you will have it all of your lifetime. There is no need for treatment and most people who have inherited this are not sick and probably do not know they have it. A mild form of Thalassemia minor may be mistaken for iron deficiency anemia. Iron medicines are not usually necessary and will not help your anemia. They could even be harmful if taken over a long period of time.

If you marry a person who does not have Thalassemia Minor, your children may have Thalassemia Minor. If you marry a person who does have Thalassemia Minor, some of your children may have Thalassemia Major. You must decide if you want to take this risk in planning your family.

Symptoms of Thalassemia Major
An infant with Thalassemia Major appears normal at birth. If a child is well for the first five years of life, a diagnosis of Thalassemia Major is unlikely. The double dose of two Thalassemia genes causes an anemia that is so severe that regular blood transfusions must be given throughout life

A newborn with Thalassemia Major appears normal at birth. As they grow, infants with Thalassemia Major exhibit paleness and fussiness. Weakness and slow growth appear in the first or second years of life. The abdomen may swell due to an enlarged liver and spleen. Changes occur in the appearance of the face and head. The eyes appear slanted and the cheekbones become prominent.

Treatment for Thalassemia Major
Treatment involves blood transfusions that must be given every 4 to 6 weeks to sustain life.
Complications that may arise from regular blood transfusions include an overload of iron build up in vital organs causing diabetes, liver disease and heart failure. The spleen may become so enlarged or overactive that it has to be removed surgically. In the past, many patients died in their teens due to these complications.

Management of thalassemia is not enough. Researchers are investigating two potentially curative treatments:  Stem Cell transplantation and gene therapy. Both methods have shown promise.

In stem cell Therapy, there are two ways to go about it.

  1. Bone Marrow Transplant
  2. Cord Blood Transplant

Some children with thalassemia can be cured with a bone marrow transplant. However, this form of treatment is most successful when a donor who is an exact genetic match is available. Generally, a sibling or other family member is most likely to be an exact match. The procedure can cure about 85 percent of children who have a fully matched family donor. However, only about 30 percent of children with thalassemia have a family member who is a suitable donor.

Recent studies suggest that using umbilical cord blood from a newborn sibling may be as effective as a bone marrow transplant. Like bone marrow, cord blood contains unspecialized cells called stem cells that produce all other blood cell.

The beneficial results of stem cell transplantation from HLA identical family members for patients with severe thalassemia are clear. Class I patients have a very high probability of cure with a very low early and late morbidity and mortality. Delay of transplantation until the patient is in a risk category beyond class I substantially reduces the probability of transplant success and jeopardizes the reversibility of liver and cardiac damage. It is reasonable to suggest that patients with β-thalassemia who have HLA-identical donors should be transplanted as soon as possible.

Umbilical cord blood (UCB) has been shown to be capable of reconstituting the bone marrow of the patient with thalassemia after myeloablated pre-conditioning treatment. The major advantage of UCB over other sources of stem cells is the ability to cross HLA barriers, and there is evidence of less GVHD. The use of related – donor UCB stem cells with HLA mismatches at one to three antigens needs to be considered. It would be worthwhile to do a prospective study to evaluate the role of UCB stem cell transplantation in the treatment of the thalassemias and hemoglobinopathies.

Thalassemia is widely distributed throughout the world and is one of the major public health problems. The use of bone marrow transplantation, the only curative therapy for thalassemia, is limited because less than 30% of the patients have unaffected and HLA-identical siblings as donors. Cord blood stem cells, an alternative source of stem cells for transplantation, have been successfully transplanted into patients with several diseases after myeloablative therapy.

Testing for Thalassemia
If a person has Thalassemia Minor, the cause of the slight anemia is known and no other blood tests or treatments such as iron are needed. More important, since individuals with Thalassemia Minor can pass the Thalassemia gene to their children, most people would like to know if there is a risk that their children could inherit this severe blood disease.

A safe and reliable prenatal test to diagnose Thalassemia Major in a fetus as early as 10-12 weeks after conception has been developed. Couples who are at risk may want to consider this possibility.

Success rate of Stem Cell Transplantation (SCT) for Thalassemia?
In low-risk cases (less than 10 years of age, having regular chelation therapy, non liver enlargement and no transfusion-associated diseases like hepatitis or HIV), SCT provides a 80-90% cure probability, with 5% mortality rate and a 10% chance of rejection (thus leaving the child thalassemic).

Cost of storing Umbilical Cord Blood
In Pakistan, one Company namely Cryo Cell Pakistan, with the help of their affiliate in USA, offering collection, extraction and storing services. The normal fee was about USD. 2,000 but they are offering handsome discount on their price in the introductory period. Further details may be obtained from their website

Gene therapy saved children

February 9, 2010

Courtesy by:

Research conducted in France in the field of gene therapy, in collaboration with a German team, has just resulted in an original clinical trial. The collaboration of an international group of researchers has allowed the progression of a very serious brain disorder in two young boys to be checked through the use of a totally new gene therapy technique. A success that opens up significant prospects for the treatment of many diseases.

For the first time, a brain disease has been treated effectively by gene therapy. The results of this therapeutic trial, published in the prestigious journal Science, have had a considerable impact in France and in the United States. This major scientific advance also received extensive publicity during the Telethon held on 4 and 5 December in France as part of the annual campaign to raise funds for research into genetic disorders.

Adrenoleukodystrophy (ALD) is a dreadful genetic disorder that affects one in 20,000 boys and leads, in its most serious but also most frequent form, to a breakdown of the myelin sheath of the brain through which messages are sent and received. These lesions can rapidly affect the vital functions and bring about the death of the sufferer. It was as a result of seeing children suffering from ALD in his paediatric neurology department at the Saint-Vincent-de-Paul hospital in Paris, that Professor Patrick Aubourg began his research: on developing a biochemical marker for diagnosis and treatment by bone marrow allograft, with his colleague Pierre Bougnères, as well as the paediatricians and researchers in immunology Claude Griscelli and Alain Fisher of the Necker Hospital for Sick Children. “These grafts enable us to arrest the development of brain disorders, but only after a waiting period of several months,” stresses Patrick Aubourg. “Moreover they are still dependent on finding compatible donors and can lead to complications that are often fatal”.

The new approach consists of grafting the patient’s own bone marrow cells, after treatment by gene therapy. The sample stem cells collected are corrected using a medicinal vector derived from the AIDS virus.

“An offshoot of research on AIDS, this discovery will have consequences for the treatment of patients suffering from this disease,” observes Patrick Aubourg in passing. After treatment, the stem cells are then re-injected. They then reach the bone marrow and head towards the brain where they play a corrective role.

This process, though it might appear simple, is the culmination of many years’ work. The clinical trials were conducted by INSERM, the French National Institute for Health and Medical Research, the Assistance Publique-Hôpitaux de Paris (city of Paris public hospital system), and the Paris-Descartes University of Medicine.

The innovative analysis of the development of corrected cells, carried out by the team led by Christof Van Kalle (Deutsches Krebsforschungszentrum, Heidelberg, Germany), was also a deciding factor. “Alhough we must remain cautious, this analysis shows that there is no particular reason to fear any harmful effect related to the insertion of the vector,” points out Nathalie Cartier, director of research at INSERM, who coordinated all the work.

After numerous tests, two trials were conducted in 2006, on two boys then aged 7: “more than three years later for the first child and two and a half years for the second, no worrying consequence was found,” comments Patrick Aubourg. “A third patient has been treated but it is still too soon to draw any conclusions.”

The scientists have managed up till now to correct some 15% of bone marrow stem cells and hope one day to correct 30% or even 60% of them, which would further shorten the time during which the disease continues to progress. Researchers and practitioners however stress the fact that the treatment stops the development of the disease, but does not cure it, hence the importance of early detection in high-risk families. A screening system at birth is also in the process of being validated in the United States.

Nathalie Cartier and Patrick Aubourg today envisage extending the clinical trials to other patients, in France and elsewhere. This major scientific advance is opening up new prospects by promoting the use of gene therapy vectors in the treatment of other diseases, such as thalassemia, a form of hereditary anaemia, or sickle cell anaemia, responsible for an anomaly in haemoglobin. Millions of people worldwide will no doubt eventually benefit from these cutting-edge treatments.

Ninth Cooley’s Anemia Symposium

July 13, 2009

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Thanks to scientific advances, individuals with thalassemia—a group of genetic blood disorders which includes Cooley’s Anemia—are now living into their 40s and 50s. Not only are individuals living longer, but their quality of life has increased. Scientific and clinical advancements have resulted in new iron-chelating drugs, early detection of organ failure, an understanding of adult complications associated with living with thalassemia (osteoporosis, heart failure, growth hormone defi ciency, pulmonary hypertension, and in fertility) and promising progress towards the ultimate magic bullet—a cure in the form of bone marrow and cord blood transplants, or gene therapy.

The symposium will integrate basic science and clinical research so that both scientists and clinicians can develop a mutual understanding of recent progress in thalassemia.Patients are also welcome to attend the symposium and are eligible for discounted prices. Please email or call 800. 522.7222 for more information.

The Thalassemia Action Group (TAG), the only national patient support group for thalassemia patients, will host a one-day meeting in conjunction with this conference. The meeting, to be held on Saturday October 24th from 9:00 am to 5:00 pm, is intended for patients and family members in order to educate them on presentations and scientific advancements discussed during the symposium. It is a chance for patients to hear experts on thalassemia, ask questions and discuss the concerns that face those afflicted with thalassemia. For more information please visit or email For information about registration to the TAG meeting please call 800.522.7222 (ext 205)

Call for Abstracts

The deadline for abstract submissions is Friday, August 14, 2009. For complete abstract instructions, please e-mail: Type the words “Abstract Information” in the subject line—there is no need to type a message. Instructions will be forwarded automatically. Any questions, please call 212.298.8681.

Gene may open door for new sickle cell therapies

March 16, 2009

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CHICAGO (Reuters) – U.S. researchers have discovered a gene switch that could lead to better treatments for sickle cell disease and thalassemia, two inherited blood disorders that affect millions of people, they said on Thursday.

Learning how to activate this switch might help doctors direct the body to make healthier blood cells — in this case, replicating conditions found in the womb.

People with these blood disorders either make too little or abnormal forms of hemoglobin, the protein in red blood cells that is vital for carrying oxygen to the body’s tissues.

A developing fetus uses one gene to make hemoglobin, but switches to another after birth, and problems with this adult gene are what lead to sickle cell disease and thalassemia.

“One of the goals for many years has been to understand this switch of hemoglobins, with the idea that if you could understand it you could reverse it or reactivate (the fetal gene),” said Dr. Stuart Orkin of Harvard Medical School in Boston, who reported his findings in the journal Science.

Orkin and colleagues said a gene called BCL11A directly affects the production of fetal hemoglobin.

“This one is a major player,” Orkin said in a telephone interview, calling BCL11A a “silencer gene” responsible for keeping fetal hemoglobin in check. “It is probably not the only player but we think it is a significant player,” he said.

Orkin said some people continue to make fetal hemoglobin after they are born, and those who do and have sickle cell disease have much milder symptoms.

In experiments on normal human cells, Orkin said his team was able to turn off the activity of this gene, and the cells produced more fetal hemoglobin.

Orkin said the finding offers hope for new therapies, including gene therapy or new drugs that could modify the effects of the BCL11A gene.


“This is a little bit of a holy grail,” said Dr. Susan Shurin, deputy director of the National Heart, Lung and Blood Institute, which helped fund the research.

“Over the past 40 years people have looked really hard to understand what kinds of things control the switch from fetal to adult hemoglobin,” she said in a telephone interview.

“What this does is it opens up the potential for some highly targeted therapeutic intervention.”.

Shurin said an older drug called hydroxyurea, approved by the U.S. Food and Drug Administration in 1998, increases production of BCL11A, but not all patients benefit and it has some toxic side effects.

She said the research by Orkin and others really paves the way for new drug development. “It gives you methods you can use to screen agents that are likely to be effective,” she said.

In sickle cell disease, blood cells become stiff and sickle-shaped, causing them to block blood vessels and starve tissues of oxygen. In thalassemia, the body struggles to make enough hemoglobin, resulting in anemia that can leave the body prone to infection.

Sickle cell disease is the most common inherited blood disorder, affecting about 70,000 people in the United States, mostly African Americans. It affects millions of people worldwide.

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