Sickle cell disease, or sickle cell anemia, is a blood disorder which stems from a defective gene for the protein beta-globin, a component of haemoglobin. The defective gene leads to the characteristic deformed sickle shape of the haemoglobin-containing red blood cells, which adversely affects cell flexibility and hence causes disintegration and clumping. As a consequence, the blood vessels become clogged causing severe pain episodes and a series of small damaging strokes which can result in multiple organ failure. The life expectancy for sickle cell disease sufferers is about 45 years in the United States. Worldwide, sickle cell disease sufferers are in the millions.
Using a strain of mouse with essentially the same genetic defect and symptoms as humans with sickle cell disease, scientists at St. Jude Research Hospital in the USA have discovered that gene therapy can alleviate this condition in rodents to the extent that treated mice almost, or even completely, show no manifestations of the disease months after the gene transfer. Although researchers warn that similar treatment in humans is a somewhat faraway concept due to some technicalities, they agree that the successful treatment of mice is elemental in paving the way to gene therapy as a cure for humans.
The idea arose from the use of the drug hydroxyurea. St Jude researchers found that hydroxyurea reduces the symptoms of sickle cell disease by promoting the formation of an immature fetal form of hemoglobin in red blood cells. Instead of beta-globin, this immature hemoglobin - which disappears after birth - contains another form of the protein, called gamma-globin. For sickle cell disease patients, treatment with hydroxyurea is useful, and has led to the concept of gene transfer as a possible cure for the disorder, by permanently increasing fetal hemoglobin levels.
In summary, the gene for gamma-globin is inserted into blood-forming cells and the altered cells are then re-introduced into the body. After the extraction of the blood-forming cells, the gene insertion occurs via a harmless viral carrier in a culture dish. The aim is to trigger permanent production of red blood cells containing gamma-globin, to cure the disease. The outcomes of the experiment have proved to be encouraging, as months after the introduction of the altered red blood cells, gamma-globin production continued. As a result, the treated mice exhibited negligible, or zero signs of the disease. No anemia could be detected in the mice, and organ function appeared to be normal. Furthermore, in order to confirm that the gene for gamma-globin had been permanently incorporated into the blood-forming cells, the altered cells from the treated mice were transplanted into a second group of untreated sickle cell mice. The second group of mice showed similar production of gamma-globin and alleviated symptoms of the disease.
Until recently, a bone marrow transplant seemed to be the only permanent cure for sickle disease. The transplant provides recipients with blood-forming cells which form normal beta-globin. Unfortunately, this option is not available to most patients due to the scarcity of compatible donors. However, this study has revealed that gene therapy to produce fetal hemoglobin is another new possibility to correct sickle cell disease in humans. Derek Persons, M.D., Ph.D., assistant member in the St. Jude Department of Hematology, is optimistic that increasing fetal hemoglobin expression in patients seems a comparatively safe and feasible approach to a cure (for example, in comparison to bone marrow transplants), as the fetal hemoglobin is likely to be well tolerated and accepted by the immune system. Nonetheless, researchers have yet to work through technical barriers. In particular, the gene insertion rate into human cells is significantly lower than for mice cells; it is at least a hundred-fold less. St Jude researchers are currently investigating techniques to achieve a sufficiently high gene insertion rate in human cells to pave the way for gene therapy as a genuine cure for sickle cell disease.
Article:
http://www.sciencedaily.com/releases/2008/12/081203184643.htm
Using a strain of mouse with essentially the same genetic defect and symptoms as humans with sickle cell disease, scientists at St. Jude Research Hospital in the USA have discovered that gene therapy can alleviate this condition in rodents to the extent that treated mice almost, or even completely, show no manifestations of the disease months after the gene transfer. Although researchers warn that similar treatment in humans is a somewhat faraway concept due to some technicalities, they agree that the successful treatment of mice is elemental in paving the way to gene therapy as a cure for humans.
The idea arose from the use of the drug hydroxyurea. St Jude researchers found that hydroxyurea reduces the symptoms of sickle cell disease by promoting the formation of an immature fetal form of hemoglobin in red blood cells. Instead of beta-globin, this immature hemoglobin - which disappears after birth - contains another form of the protein, called gamma-globin. For sickle cell disease patients, treatment with hydroxyurea is useful, and has led to the concept of gene transfer as a possible cure for the disorder, by permanently increasing fetal hemoglobin levels.
In summary, the gene for gamma-globin is inserted into blood-forming cells and the altered cells are then re-introduced into the body. After the extraction of the blood-forming cells, the gene insertion occurs via a harmless viral carrier in a culture dish. The aim is to trigger permanent production of red blood cells containing gamma-globin, to cure the disease. The outcomes of the experiment have proved to be encouraging, as months after the introduction of the altered red blood cells, gamma-globin production continued. As a result, the treated mice exhibited negligible, or zero signs of the disease. No anemia could be detected in the mice, and organ function appeared to be normal. Furthermore, in order to confirm that the gene for gamma-globin had been permanently incorporated into the blood-forming cells, the altered cells from the treated mice were transplanted into a second group of untreated sickle cell mice. The second group of mice showed similar production of gamma-globin and alleviated symptoms of the disease.
Until recently, a bone marrow transplant seemed to be the only permanent cure for sickle disease. The transplant provides recipients with blood-forming cells which form normal beta-globin. Unfortunately, this option is not available to most patients due to the scarcity of compatible donors. However, this study has revealed that gene therapy to produce fetal hemoglobin is another new possibility to correct sickle cell disease in humans. Derek Persons, M.D., Ph.D., assistant member in the St. Jude Department of Hematology, is optimistic that increasing fetal hemoglobin expression in patients seems a comparatively safe and feasible approach to a cure (for example, in comparison to bone marrow transplants), as the fetal hemoglobin is likely to be well tolerated and accepted by the immune system. Nonetheless, researchers have yet to work through technical barriers. In particular, the gene insertion rate into human cells is significantly lower than for mice cells; it is at least a hundred-fold less. St Jude researchers are currently investigating techniques to achieve a sufficiently high gene insertion rate in human cells to pave the way for gene therapy as a genuine cure for sickle cell disease.
Article:
http://www.sciencedaily.com/releases/2008/12/081203184643.htm
