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Spleen's Role In Thal - Breakthrough under way? Introducing healthy cells into the spleen as a possible cure

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Narendra:
May be we are on a breakthrough for spleen issues with thalassemia. Read below

From:- http://www.cooleysanemia.com/bodies/body407.php

Weill Cornell Study Examines Spleen in Thalassemia


--- Quote ---May 22, 2008 - Researchers from Weill Cornell Medical College may have discovered the precise role of a gene in beta-thalassemia, which may help to prevent removal of the spleen in patients. The research is published in the latest online issue of the journal Blood, the official publication of the American Society of Hematology (ASH).

In thalassemia, hemoglobin -- the oxygen-carrying molecule on red blood cells -- is mutated and non-functioning, resulting in a low red-blood-cell count. Common symptoms include an enlarged spleen, called splenomegaly, caused by a buildup of malformed red blood cells within the body. The spleen works to filter out these unhealthy cells in order to protect the body from harm, such as in a stroke, but eventually the spleen becomes over-stuffed and is commonly surgically removed (splenectomy) in order to prevent a potentially fatal burst. Unfortunately, after the spleen is removed, patients are at a much greater risk for stroke and infections.

Dr. Stefano Rivella, the study's senior author and assistant professor of genetic medicine in pediatrics at Weill Cornell Medical College, in New York City, believes that he and his collaborators may have found a way around splenectomy. After giving mice with Cooley a compound called JAK2 inhibitor, the researchers found that the mice's spleens shrunk to normal sizes, and they began to produce normal red blood cells. The chemical (a similar compound is already in a Phase I clinical trial for myelodysplastic syndromes -- another blood disorder) blocks the activity of the JAK2 gene that is highly expressed in Cooley's anemia, and is believed to play a crucial role in the malformation of red blood cells.
After splenectomy, patients are considered immunocompromised, and so should be placed on lifelong prophylactic oral antibiotics. Patients should also be vaccinated against common viral infections, and should receive annual influenza vaccinations.

Researchers are still learning about the health effects that stem from years of living with reduced or deficient globin proteins. An emerging realization is that removal of the spleen can cause an increase in the risk of life-threatening blood clots. Splenectomy is common for thalassemia patients because their red blood cells are crippled or dead, so the spleen has to work overtime and can become enlarged.

Researchers disagree on the degree of risk associated with splenectomy. A study by Dr. M. Domenica Cappellini, a co-author of this research, found that 30 percent of splenectomized thalassemia intermedia patients developed clots. However, a recent study of 8,860 splenectomized patients with thalassemia major and thalassemia intermediate found that the rate of thrombolytic events was 1.75 percent.

Surgical technique has played a role in developing clots (thrombosis). A recent study found that patients who underwent open splenectomy had a 19 percent chance of developing life-threatening clots, whereas patients who had laparoscopic surgery had a 55 percent chance.

Researchers are only now discovering why splenectomy leads to clots. Injury of endothelial cells may lead to a coagulation cascade, involving the activation of endothelial adhesion proteins, monocytes, granulocytes and platelets. Alternatively, the splenectomy might result in an imbalance between coagulation factors and anticoagulation factors. Dr. Cappellini has recommended short-term anticoagulants such as heparin after surgery, and prophylactic anticoagulants any time thalassemic patients are exposed to thrombolytic risk factors such as surgery, prolonged immobilization or pregnancy. Oral contraceptives should be avoided because they carry their own risk of thrombosis.

This study was funded by grants from the National Institutes of Health (NIH), the Carlo and Micol Schejola Foundation, the Roche Foundation for Anemia Research (RoFAR), the Cooley's Anemia Foundation (CAF), the Children's Cancer and Blood Foundation (CCBF), the Associazione per la Lotta alla Talassemia di Rovigo (AVLT), and the American Portuguese Biomedical Fund.

Dr. Rivella's co-authors and collaborators include Drs. Ilaria Libani, Ella Guy, Luca Melchiori, Raffaella Schiro, Pedro Ramos, Laura Breda, Amy Chadburn, YiFang Liu, Matteo Porotto, Patricia Giardina and Robert Grady -- all of Weill Cornell Medical College in New York City; Dr. M. Domenica Cappellini, as well as Dr. Libani, of Centro Anemie Congenite, the University of Milan; Dr. Maria de Sousa, as well as Dr. Ramos, of Iron Genes and Immune System (IRIS) Lab, Oporto University, Portugal; Drs. Thomas Scholzen, Margrit Kernbach, Bettina Baron-Luehr and Johannes Gerdes, of Research Center Borstel, Germany; Dr. Eliezer Rachmilewitz, of E. Wolfson Medical Centre, Israel; and Dr. John Hood, of TargeGen, Inc., San Diego.


About Weill Cornell Medical College
Weill Cornell Medical College -- Cornell University's Medical School located in New York City -- is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, AIDS, obesity, cancer, psychiatry and public health -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. The Medical College -- in its commitment to global health and education -- has a strong presence in such places as Qatar, Tanzania, Haiti, Brazil, Austria, and Turkey. With the historic Weill Cornell Medical College in Qatar, the Medical School is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the world's first clinical trial for gene therapy for Parkinson's disease, and, most recently, the first indication of bone marrow's critical role in tumor growth. For more information, visit www.med.cornell.edu.
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§ãJ¡Ð ساجد:
Thanks Narendra! great sharing :)

This is impressive!

I hope this becomes a practical reality soon.

It would have a positive impact on all issues relating to missfunctioning spleen.

Hopefully something like this be found for the Stem cells in our BMT and make it work normally too

:pray

Canadian_Family:
Thanks for sharing.

Bobby:
Awesome!!! I'm definately keeping my spleen for the time being now. Thanks.  :hugfriend

Sharmin:
I had an interesting thought - which may or may not be of value, but I think it is worth considering.

I know of a case - in which a hemophiliac patient received a liver transplant (because his own liver was defective).  A result of this transplant, which was not predicted, is that the transplanted liver now produces the factor he is missing therefore he no longer has hemophilia.  His underlying disease has been cured.

In the same way, the spleen is capable of producing red blood cells - which is one of the reasons why it becomes enlarged in thalassemia (in hopes to increase its surface area to produce red blood cells - but the lack of beta genes makes it impossible for the spleen to do so).  Would a spleen transplant - or even introducing spleen tissue or genes to a thal major patient's spleen possibly have a curative effect on thalassemia?  Would it not be easier, perhaps safer than a bone marrow transplant or gene therapy targeting the bone marrow?  Maybe this would decrease the need for chemotherapy in gene therapy (which is used for marrow ablation to make room for the corrected cells).   

What do you think Andy?  I have cooked this up in my own head I don't know if it makes any sense...

Sharmin

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