Hormone’s Crucial Role in Two Anemic Blood Disorders

November 24, 2010

Courtesy: healthnewsdigest.com

A hormone made by the body may be a potential therapeutic tool for the treatment of two anemic blood disorders — beta-thalassemia and hemochromatosis. The new research was led by scientists at Weill Cornell Medical College and published in the Journal of Clinical Investigation and the journal Blood.

Commonly known as Cooley’s anemia, beta-thalassemia affects nearly 1,000 individuals in the United States; worldwide, approximately 300,000 children are born each year with thalassemias. The conditions cause excessive iron absorption in the body’s organs, with symptoms including fatigue, liver disease, heart failure, growth impairment, diabetes and osteoporosis. Standard treatment involves regular blood transfusions, which are often ineffective, or bone marrow transplants, which can help to replace and repair the broken blood production of the body.

Hepcidin, a hormone found naturally in the bloodstream and acting at the level of the digestive tract, has been known to be at low-levels in patients with beta-thalessemia. Now, the researchers have evidence that boosting levels of hepcidin may actually have a direct effect in relieving anemic patients of their body’s iron overload, potentially relieving the ravages of these conditions.

“The major consequence of iron-overload is that the lifespan of a red blood cell is half that of a normal red blood cell. These blood cells are not properly formed, are not as healthy as normal blood cells, and, therefore, cannot properly function,” explains Dr. Stefano Rivella, associate professor of genetic medicine in the Department of Pediatrics at Weill Cornell Medical College.

In the Journal of Clinical Investigation study published online on Nov. 22, Dr. Rivella and his colleagues report that breeding mice that overproduce hepcidin with other mice suffering from beta-thalassemia led to offspring that were almost as healthy as normal mice. However, when they crossed the hepcidin-expressing mice with normal mice, hepcidin levels were too high, leading to too much iron removal and an inability to produce healthy red blood cells.

“We see from this evidence that there is a balance in the body — not too much iron and not too little iron — that must be maintained to keep iron levels normal in order to produce normal blood cells,” says Dr. Rivella.

He explains that under normal conditions, hepcidin recognizes when there are not enough red blood cells. In turn, the body will then produce the correct amount of hepcidin, which regulates the amount of iron needed.

“In patients with beta-thalassemia, this mechanism isn’t working — it’s as if the raw materials — the iron — are being sent into a factory, but since no products — blood cells — are being made, more and more iron is being sent in and stored in the body’s organs,” explains Dr. Rivella.

Hepcidin’s Influence on Hemochromatosis and Iron Overload
A second study published in a recent issue of the journal Blood, and authored by Dr. Rivella and his lab, illustrates a potential new dietary treatment for patients with hemochromatosis. This anemic disease is caused by a mutation to the HFE gene, leading to lowered production of hepcidin. The disorder affects nearly 1.5 million individuals in the United States.

Hemochromatosis interferes with the body’s ability to break down iron, resulting in too much iron being absorbed from the gastrointestinal tract. Like in beta-thalassemia, patients often have iron buildup within the liver, which could lead to liver failure and sometimes liver cancer.

For treatment, patients often have blood taken out of their body, called phlebotomy. Doing so is believed to force the body to remove iron from the liver, reducing iron overload within the organ. Patients return regularly to the doctor’s office to have blood removed, in order to lower iron levels in the body, but the procedure is not so effective and could be improved, as Dr. Rivella and his colleagues describe in their study.

“We’ve learned that in hemochromatosis the body will always look to the diet in the gut for iron and not take it from the liver,” explains Dr. Rivella. “Therefore, a low-iron diet immediately following phlebotomy may force the body to look primarily to the liver for its iron supply.”

To test their hypothesis, Dr. Rivella tested three different groups of mice: normal mice on a normal diet (group 1), normal mice given a high-iron diet (group 2), and mice with hemochromatosis on a normal diet (group 3). Group 2 was given a high-iron diet in order to raise iron levels in the liver, similar to mice in group 3.

Each group had blood removed through phlebotomy and then had their hepcidin levels tested. A low level of hepcidin would indicate that the hepcidin is being utilized to absorb iron from the gut.

Results indicated that group 1 behaved as expected: Blood was removed and found to have low levels of hepcidin, meaning that the body was absorbing iron from the digestive tract.

Group 2 had higher levels of hepcidin because the body was able to recognize that there was a reservoir of iron within the liver, illustrating that hepcidin was needed to prevent the iron from being absorbed from the gut.

However, the levels of hepcidin in group 3 was low because the body was unable to recognize a high level of iron in the liver because a genetic mutation lowered the production of hepcidin, resulting in iron being taken from the gut instead of the liver.

“The implications of these findings are that if you take out the blood from patients with hemochromatosis, the body will still look to take readily available iron from the diet, instead of from the overloaded iron packed in the liver,” explains Dr. Rivella.

Recently, Dr. Rivella and collaborators at UCLA were awarded a $4 million grant from the National Institutes of Health to test a drug that mimics hepcidin in people with beta-thalassemia and hemochromatosis. They hope to show that boosting hepcidin in the body helps to better treat their iron overload and anemia.

First author of the Journal of Clinical Investigation study is Dr. Sara Gardenghi of Weill Cornell Medical College. Co-authors include Pedro Ramos, Maria Franca Marongiu, Luca Melchiori, Laura Breda, Ella Guy, Kristen Muirhead, Niva Rao, Patricia Giardina and Robert Grady, all from Weill Cornell Medical College; Cindy Roy, from Johns Hopkins University School of Medicine, Baltimore, Md.; Nancy Andrews, from Duke University School of Medicine, Durham, N.C.; Elizabeta Nemeth, from the David Geffen School of Medicine, University of California, Los Angeles, Calif.; Antonia Follenzi, from Albert Einstein College of Medicine, Bronx, N.Y.; Xiuli An and Narla Mohandas, from the Red Cell Physiology Laboratory, New York Blood Center, New York, N.Y.; Yelena Ginzburg, from the Erythropoiesis Laboratory, New York Blood Center, New York, N.Y.; and Eliezer A. Rachmilewitz, from the Hematology Department, Edith Wolfson Medical Center, Holon, Israel.

Research conducted in the JCI study is supported by funding from the National Institutes of Health, the Cooley’s Anemia Foundation, the Associazione Veneta per la Lotta alla Talassemia, the Carlo and Micol Schejola Foundation, the Children’s Cancer and Blood Foundation, and the American Portuguese Biomedical Research Fund.

First author of the Blood study is Dr. Pedro Ramos of Weill Cornell Medical College. Co-authors include Ella Guy, Nan Chen, Sara Gardenghi, Carla Casu, Catia C. Proenca and Robert W. Grady — all from Weill Cornell; Antonia Follenzi, from the Albert Einstein College of Medicine, Bronx, N.Y.; Nico Van Rooijen, from the Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands; and Maria de Sousa, from the Instituto de Ciências Biomédicas de Abel Salazar, Porto, Portugal.

Research conducted in the BLOOD study was supported by grants from The National Institutes of Health, the Carlo and Micol Schejola Foundation, the Children’s Cancer and Blood Foundation, and the American Portuguese Biomedical Research Fund.

Four children of a family suffering from Thalassemia shifted to Lahore

November 24, 2010

Courtesy: brecorder.com

Four children of a family suffering from Thalassemia have been shifted to Jinnah Hospital Lahore from Dera Ghazi Khan along with their parents for treatment.

An official handout issued here said that in response to the instructions of Chief Minister Punjab Muhammad Shahbaz Sharif, Secretary Health Fawad Hassan Fawad has constituted a medical board comprising senior doctors for the medical examination of the four children of a family of Dera Ghazi Khan, who are suffering from Thalassemia.

The medical board will comprise Professor Riaz-ud-Din, Professor Shaheen, Professor Tariq Bhatti, Professor Nosheen Yousuf, Professor Mefooz-ur-Rehman, Dr Shehla Tariq and Dr Ali Java.

The medical board will hold a meeting at the office of Secretary Health Punjab on Monday and submit its report regarding the treatment of the children, which will immediately be sent to the Chief Minister. The children and their parents have been shifted to Jinnah Hospital, Lahore from Dera Ghazi Khan by ambulance.

Genetic infertility treated successfully at Mumbai hospital

November 24, 2010

Courtesy: dnaindia.com

A woman with a rare genetic disorder ‘Robertsonian Translocation’, resulting in infertility, has delivered a healthy baby girl at the Jaslok Hospital and Research Center.

“With this first Invitro fertilisation (IVF) using pre-implantation genetic diagnosis (PGD), India joins a handful of countries that have accomplished successful management of this disorder,” Dr Firuza Parikh, Director, Assisted Reproduction and Genetics at Jaslok and former Professor at the Yale University School of Medicine, USA, said.

The baby girl was delivered yesterday at city’s Jaslok hospital, Parikh said adding that this case report was published as a cover article in the peer reviewed ‘Journal of Prenatal Diagnosis and Therapy’ (January- June 2010).

Attributing the success to her team of 40 individuals particularly Dr Prochi Madon, Dr Arundhati Athalye, Mr Nandkishor Naik and Dattatray Naik, Parikh explained, “We are born with 46 chromosomes which occur in pairs. Each chromosome of a pair is a mirror image of the other. Although this harmony ismaintained in nature, an occasional slip results in a translocation.”

“As the name suggests, a segment or an arm of one chromosome transports itself onto another chromosome and one such rearrangement is called a RobertsonianTranslocation after the American geneticist Dr W Robertson,” she said.

“The rearrangement can occur in males and females who do not manifest any clinical symptoms. The problem manifests when the couple tries to conceive,” Parikh said.

“An embryo derives half its chromosomes from the father and half from the mother. Hence if the chromosome with extra genetic material goes into the embryo, the amount of genetic material of that chromosome triples resulting in miscarriage or mental retardation,” the In-vitro fertilization (IVF) expert said.

The embryos were screened using Pre-implantation Genetic Diagnosis (PGD).

Eleven years ago, Parikh and Madon established PGD for genetic disorders for the first time in India at the Jaslok Hospital and Research Centre.

Parikh who led this procedure, said, “PGD requires years of perfection, team work and a thorough knowledge of reproductive biology and genetics. The couple first undergoes IMSI (intracytoplasmic morphologically selected sperm injection).

In this procedure the egg and the sperm are magnified 7000 times. With the help of a sharp pipette a single sperm is injected into the egg and the resulting embryo is ready for PGD when it reaches the eight cell stage.”

“A laser beam swiftly cuts open the shell of the embryo, a fine glass pipette is advanced towards one of the cells of the embryo. Using gentle suction, a single cell is aspirated. This cell is then processed by the genetics team,” Parikh said.

Madon, chief geneticist added, “The cell is put through an overnight procedure called Fluorescence In Situ Hybridisation (FISH), a procedure to zip open the DNA strands and attach coloured probes, to identify the chromosomes of interest.”

In this particular couple, the wife had a translocation between chromosomes 13 and 14. Two embryos underwent the procedure of PGD. This embryo was transferred into the mother’s womb, resulting in the birth of a healthy baby girl.

“PGD is an effective form of treatment for couples at a risk for Down Syndrome and other chromosomal abnormalities, for women approaching 40, those with repeated failed attempts at IVF/ICSI (Intracytoplasmic sperm injection), those women showing poor quality embryos and for severe male factor infertility. It is also helpful in some rare genetic diseases like haemophilia,” Parikh said.

“We are now in the process of setting up a facility for PGD to detect embryos at a risk of Thalassemia. We have also started offering this procedure routinely to couples undergoing IVF/ICSI in order to select normal embryos so that less number of embryos are transferred,” she said.

This will increase the chances of a normal pregnancy and decrease the chances of a miscarriage. This technique is called pre-implantation genetic screening (PGS), Parikh added.

Resident Continues Fight For Cooley’s Anemia Cure

November 24, 2010

Courtesy: gcnews.com

At 88 years old, Garden City resident Concetta Paradiso continues to dedicate much time and energy to raising awareness and funds to find a cure for Cooley’s Anemia, a fatal, genetic blood disorder affecting thousands of children.

“People ask me sometimes, ‘Haven’t you had enough?’” Concetta said in a published interview. “Sometimes I’d like to quit, but then I think about it, about how we still don’t have a cure, and I decide to keep on. There are a lot of things going on now in the search for a cure. I hope they find it, and soon.”

Concetta and her late husband Edward had four children: Susan was born in 1949, Peter in 1950, Janice in 1954 and Paul in 1956. Susan and Paul were diagnosed with Cooley’s Anemia during early childhood; after valiant battles, they both ultimately succumbed to the disease, Paul at 17 and Susan at 28 years of age.

Cooley’s Anemia, also known as thalassemia, is the name of a group of genetic blood disorders. Red blood cells consist partially of hemoglobin, which carries oxygen throughout the body. Hemoglobin consists of two different proteins, an alpha and a beta. If the body does not produce enough of either of these two proteins, the red blood cells do not form properly and cannot carry sufficient oxygen. The result is anemia.

Treatment involves blood transfusions every two to three weeks and folate supplements. The disease is fatal because transfusions increase the level of iron in the body. The excess iron collects around organs, including the heart, and ultimately causes them to fail.

The hope for a cure is getting closer each day. Through the years there have been several medical breakthroughs that have made it easier for patients to manage the disease. Many now survive into their 50s.

“The Foundation has research projects that are very promising,” said Janice Cenzoprano, Concetta and Edward’s daughter and member of the local foundation’s executive committee. “They need the funds to continue the research. For the past 40 years, the Garden City community has been generous in donating the funds needed for research, which has added 10 to 15 years onto the lives of children born with Cooley’s Anemia.”

Concetta and Edward joined the national Cooley’s Anemia Foundation in 1956 when Paul was four months old. They became involved in fundraising and organizing blood drives. Concetta served as secretary and Edward became president, a post that Concetta also later assumed.

Eventually, they were two of the primary founders of the local CAF chapter based in Garden City. Concetta continues to raise awareness and funds for research and development. The local chapter hosts four major events a year: a brunch in March, a walkathon and a golf outing in May and a dinner dance in November

Teen thankful for gift of life

November 24, 2010

Courtesy: mississauga.com

A Mississauga teen who needs frequent blood transfusions to stay alive thanked blood donors personally last week.

Now 14, Olivia Vitelli was just five months old when she had her first blood transfusion after suffering a stroke. At nine months, she was diagnosed with thalassemia and began receiving regular blood transfusions every three to four weeks.

Thalassemia is an inherited blood disorder that results in chronic anemia. There is no known cure.
She’ll likely have to have those transfusions for the rest of her life.
Together with her mom Ida Vitelli, they thanked donors at clinic held Friday at the Canadian Coptic Centre. The clinic was dubbed “In Honour of Olivia.”

“It’s a chance for people to see and talk to someone who really needs blood, and who will chronically need it for the rest of her life. It’s why we’re doing this,” said Ida, who encouraged Mississauga residents to come out and give blood.

“On average, every minute of every day, someone in Canada needs blood,” said Helena Hearn, the community development coordinator at Canadian Blood Services. “We need more donors and we need more youth donors to get engaged and get involved in the blood system. Giving blood is one of the most direct ways you can help someone. So we encourage Mississauga residents to come out and help patients in need — patients like Olivia.”

Salman pledges bone marrow to help patients

November 23, 2010

Courtesy: Thaindian.com

Bollywood star Salman Khan’s philanthropic side is well known and now the actor has gone ahead and pledged his bone marrow to help people suffering from life-threatening diseases.

“Donating marrow is a simple act, it’s as simple as donating blood. But this simple act can save the life of someone suffering from blood cancer, thalassemia and other major blood-related diseases,” Salman said in a statement.

“I am pledging my marrow with MDRI (Marrow Donor Registry of India) so that in an emergency, if a patient’s sample matches mine, I can be reached to donate my marrow,” the 44-year-old actor said.

Salman’s charitable foundation Being Human has also joined hands with the Marrow Donor Registry (India) to create awareness of how marrow donors can save lives.

“The more the donors, the more lives we save. So I urge that all of you who are blessed with good health come forward and pledge your marrow so that the less fortunate can benefit from this thoughtful act,” Salman said.

The aim of the initiative is to develop a large pool of voluntary marrow donors for transplants that are life saving for patients suffering from blood cancer, thalassemia, aplastic anemia, congenital immunodeficiency states and other such blood related diseases.

UK molecular scientist presented with prestigious Lasker Award

November 23, 2010

Courtesy: bionews.org.uk

The Lasker Foundation has awarded UK scientist, Professor David Weatherall from Oxford University its prestigious Lasker-Koshland Award for Special Achievement in Medical Science. The award is seen as America’s equivalent of the Nobel Prize for Science. Professor Weatherall’s career spans over 50 years and he is recognised as a leading molecular researcher of blood disorders, and particularly thalassemia.
During his career, he was instrumental in forging links between medicine and basic science, recognising that many disorders have a molecular origin. He also played a key role in setting up long-term research partnerships with communities affected by thalassemia across the world, and his book on blood disorders is regarded as the definitive text in this field.

Thalassemia is an inherited blood disorders where the body makes fewer healthy red blood cells and less haemoglobin than normal. Individuals with this condition can have mild or severe anaemia.

Haemoglobin plays a key part in carrying oxygen from the lungs to the rest of the body, and scientists now know that this consists of four protein chains – two alpha globin and two beta globin. Six genes are needed to make enough of these chains, four for the alpha chain and two for the beta chain.

Thalassemia is divided into two main types, alpha and beta, and these relate to defects in the respective chains. People with alpha-thalassemia can have one or more missing genes, and have moderate or severe anaemia, depending on the number of missing genes. Individuals with beta-thalassemia have one or both genes altered.

When this hypothesis was proposed, scientists were unable to separate the two chains, but Professor Weatherall and his team developed a method to separate them and measure the relative rates of production of each chain. Therefore proving that the disease was caused by an imbalance in the production of each chain.

Professor Weatherall and his colleagues went on to define a number of other blood disorders, and he is also credited with describing the first gene deletion directly linked to human disease, a severe form of thalassemia where infants are stillborn because they were unable to produce the alpha chain of haemoglobin.

Professor Weatherall and his researchers also helped develop prenatal genetic screening for thalassemia, and improved treatments for children with the condition. Blood transfusions were found to control the symptoms of thalassemia, but over time, this leads to a build up of iron in the blood which can lead to heart failure when children reach their mid-teens. He and his team were able to adapt an existing technique which removed the excess iron, known as ‘chelation-therapy’ so that children could be treated as they slept.

Professor Weatherall has helped improve the lives of people with thalassemia throughout the world and this award is a testament to that work.

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