Scientists correct sickle cell disease in mice By Julie SteenhuysenPosted 2011/10/13 at 2:31 pm EDT CHICAGO, Oct. 13, 2011 (Reuters) - U.S. scientists have found a way to get mice with a form of sickle cell disease to make normal red blood cells, offering a potential new way to treat the blood disorder in people, they reported on Thursday. Adults with sickle cell disease make mutant, sickle-shaped forms of hemoglobin, the protein in red blood cells that is vital for carrying oxygen to the body's tissues. These deformed cells block small blood vessels, causing pain, strokes, organ dysfunction and premature death. But this problem occurs only after birth. During development, a fetus uses one gene to make a fetal form of hemoglobin, but switches to another after birth, and problems with this adult gene are what lead to sickle cell disease. A team led by Dr. Stuart Orkin of Harvard Medical School, Children's Hospital and the Howard Hughes Medical Institute in Boston, earlier had discovered that a protein called BCL11A is responsible for making the switch from fetal hemoglobin to adult hemoglobin. In the latest study, published in the journal Science, the team looked to see what would happen if they blocked production of the BCL11A protein in mice with sickle cell disease. They found that when the protein was disabled, the mice switched back to producing fetal hemoglobin. And mice that once exhibited symptoms of sickle cell disease improved. "This discovery provides an important new target for future therapies in people with sickle cell disease," Dr. Susan Shurin, acting director of the NIH's National Heart, Lung, and Blood Institute, which co-funded the study, said in a statement. "More work is needed before it will be possible to test such therapies in people, but this study demonstrates that the approach works in principle." Sickle cell disease affects 100,000 Americans and 3 million to 5 million people globally. It is most prevalent in people of African, Hispanic, Mediterranean and Middle Eastern descent. There is no widely available cure. Bone marrow transplants work for some patients, but the treatment is risky and only available to patients with relatives who can donate compatible and healthy bone marrow to them.
Very cool study! Say you can inactivate this BCL11A protein though. What are the long term effects of using fetal hemoglobin as a adult? It has a greater affinity for oxygen than adult hemoglobin, which means it will deliver oxygen to the muscles with notably less efficiency. Perhaps such side effects are less worse than having sickle cell though...?
[quote name='"eric111e"']I guess there's hope for Prodigy after all[/quote] You would know that prodigy has sickle cell.
I knew he had sickle cell. He rapped about it in one of his songs. Cant remember which. Either way, Its great that we might have made a step ahead in curing the disease all together. Just hope that there isnt some other mutation caused by disabling BCL11A. Not trying to fight an I Am Legend zombie/human.
I wonder what the long term implications will be for certain Africans, if sickle cell disease is cured, given the malaria immunity it grants them.
Yep...there's the rub...Millions more would die from malaria if SCA were eradicated, unless there were also found a way to leave SCA's benefits intact. A conundrum. MelT
I just went to a seminar the other day, where a chemist spoke of the results from bioassays on a series of quinoline analogues she made. Can't remember the exact name/probably don't want to say for IP reasons, but they're active in the nanamolar range. Could come full circle, you never know. I can't imagine that they would find a way to harvest the best of both worlds. From my understanding, the mechanism through which the sickle cell disease prevents malaria is simply that the very action of malaria on a red blood cell kick starts the 'sickle cell process', for lack of better words, and the now 'sickled' cell kills the malaria in a sacrificial manner. Without the sickle cell abnormality, the cell would go on living happily, thus providing a stable home for a 'budding' virus. But, I am no biologist, and there could be a silver lining to it, or I could have it all wrong!