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

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Offline Narendra

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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

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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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Offline §ãJ¡Ð ساجد

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #1 on: July 03, 2008, 02:09:11 PM »
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
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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #2 on: July 03, 2008, 05:51:32 PM »
Thanks for sharing.
Regards.

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Offline Bobby

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #3 on: July 08, 2008, 05:13:40 AM »
Awesome!!! I'm definately keeping my spleen for the time being now. Thanks.  :hugfriend

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Offline Sharmin

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #4 on: July 27, 2008, 04:56:48 AM »
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
« Last Edit: July 27, 2008, 06:49:34 AM by sharmin »
Sharmin

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Offline Andy Battaglia

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #5 on: July 27, 2008, 04:33:47 PM »
Sharmin,

That is a very interesting idea, especially in light of what has been found with experiments using a spleen transplant as a way to increase tolerance of further transplants, such as other organs.

http://www.medicalnewstoday.com/articles/53021.php

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...the induction of immunological tolerance is feasible through spleen transplantation...spleen transplantation in miniature swine...Spleen transplant recipients received a short course of immunosuppressive therapy, after which the transplanted spleen was accepted. The recipient became unresponsive towards the donor in vitro, allowing a kidney from the same donor to be accepted without immunosuppression. One of the possible mechanisms leading to tolerance though spleen transplantation, is the fact that hematopoietic stem cells from the donor spleen engraft in the recipients lymphoid organs, including the bone marrow, thereby teaching the immune system to consider the donor as "self".


What I find most interesting about this is that hematopoietic stem cells engraft in the patient's bone marrow. Hematopoietic stem cells are the precursors of all blood cells. In this study, the hematopoietic stem cells acted as the recipient's own stem cells. The application in thalassemia would depend on how well these stem cells reproduced and and their longevity. If the change is permanent, it may provide some real help to thalassemics.

Perhaps Dr Vichinsky can tell you if this could have some real application in thalassemia in the future.
Andy

All we are saying is give thals a chance.

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Offline Sharmin

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #6 on: July 28, 2008, 02:17:20 AM »
I will definitely mention this to Dr. Vichinsky.   

Ever since I heard of the outcome for the hemophilia patient - I have been wondering about this.  I know that the spleen is capable of extramedullary hemopoiesis - in addition the study you quoted mentions that the spleen causes engraftment in the host bone marrow.  I wonder if a spleen transplant - or even engraftment of some spleen tissue could result in some benefit - or a potential cure for thalassemia.  If the spleen can produce red blood cells - and the engrafted cells in the marrow also produce blood cells there may be potential.   

If this does not cure thal, at the very least it can reduce complications in BMT - such as GVHD - and may increase survival rates. 

We may be on to something Andy hmmmm  :dunno :dunno...

Sharmin  :biggrin
Sharmin

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Offline §ãJ¡Ð ساجد

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #7 on: July 28, 2008, 05:32:08 AM »
Sharmin, You're a genius!! :thumbs
:stars
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Offline Zaini

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #8 on: July 28, 2008, 03:21:42 PM »
Oh my God,

Great idea Sharmin  :hi5girls

This site is full of geniuses,i think i am the only dumb one  :heehee

ZAINI.
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Offline Sharmin

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #9 on: July 28, 2008, 04:25:54 PM »
Thanks Sajid and Zaini  :blush ,

Andy is our genius, I'm just a mom thinking up crazy ideas and bouncing them off of poor Andy - hoping that something makes sense.  You are right Zaini, this site is full of some very intelligent and knowledgeable people including you!  Isn't it amazing how much we can learn when we need to for our children! 

I will mention this to Dr. Vichinsky to see if this has been looked into previously. 

I hope our appointment goes well,

Sharmin
Sharmin

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Offline poo gill

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #10 on: September 29, 2008, 11:21:38 AM »
Hey Guys / Sharmin

Any news on this.?


Actually I had no idea that spleen can produce RBC's, I was only aware that spleen just protects the body and destroys the unwanted stuff in human body. Therefore it cannot distinguish the  thal rbc's to the normal rbc's as thal rbc's are not normally shaped.

"We are like angels with just one wing. We can only fly by embracing each other." 

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Offline Manal

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #11 on: September 29, 2008, 02:37:48 PM »
Sharmin, did you ask him about this subject???

manal

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Offline Sharmin

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #12 on: September 29, 2008, 03:20:58 PM »
Hi guys,

I did mention this during my July visit.  I did not have a chance to see Dr. Vichinsky at the time but I mentioned it to his associate.  He said that he had not heard of anyone attempting to transplant cells into the spleen.   He said that he would give it some thought, I have not heard back.  I think they were more concerned with getting my son's antibodies and iron levels under control at the time.  I will definitely bring it up again. 

My son's doctor however, (and he is the best doctor in our city) thought that the idea had potential especially in light of the surprising results they had in hemophilia and engraftment of liver tissue.  The spleen is definitely capable of extramedullary hemopoiesis.  Remember with thalassemia we just need some benefit, if certain cells in the body can make red blood cells it may be enough.  Also, considering that when cells are transplanted to the spleen some are also engrafted into the bone marrow.  If the spleen has already accepted these cells gvhd should not occur.   Of more benefit would be to target the spleen in gene therapy and then to attempt an autologous introduction of cells into the spleen.  It would be much better than having to ablate the marrow with chemotherapy. 

OH no there I go again making up my own science!! 

Let's see what the experts say!

Sharmin
Sharmin

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Offline Sharmin

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #13 on: October 10, 2008, 06:40:24 PM »
Andy,

Has there been any discussion at the conference along these lines? 

Sharmin
Sharmin

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Offline Andy Battaglia

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Re: Spleen's Role In Thal - Breakthrough under way?
« Reply #14 on: October 10, 2008, 07:02:29 PM »
I wish I could say that there was a lot of new material at the conference, but when I see an article presented that I downloaded long ago and see the same presentations twice by different doctors, I can't honestly say that this conference had enough new material. That isn't to say that there weren't some really good presentations, particularly those from the top doctors, Wood, Piga, Porter, etc. Wood's presentation on the treatment of heart failure in thals should be the gold standard for every thal treating hospital in the world. I will talk more about this later. For me, the conference was very successful and I accomplished a great deal, but that is due to my own efforts. More to come.
Andy

All we are saying is give thals a chance.

 

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