Researchers at Johns Hopkins have taken an important step toward a more effective treatment for some patients with sickle cell disease who require frequent transfusions.

In the study, which appeared in the journal Stem Cells, researchers say they have successfully corrected a genetic error in stem cells in these patients, then used those cells to grow mature red blood cells free from the genetic defect that causes sickle cell disease.

Sickle cell disease is the most common blood disorder in the United States, according to the National Human Genome Institute, affecting about 80,000 Americans. The disease is most prevalent among African-Americans but also occurs in Hispanic Americans. About 1 in 12 African-Americans and approximately 1 in 100 Hispanic Americans carry the sickle cell trait.

Sickle cell disease is the result of a mutation in the hemoglobin-Beta gene found on chromosome 11. Bone marrow transplantation is the currently the only cure for the disease. Unfortunately, a healthy matched sibling donor is available in only about 18 percent of children with sickle cell.

Bone marrow transplantation for sickle cell disease is also a risky procedure, with a 95 percent three-year survival rate for those with a sibling donor and 73.4 percent for those who receive a bone marrow transplant from an unrelated donor.

Bone marrow transplants can potentially cure sickle cell disease, but the patients who cannot tolerate the transplant procedure or experience transplantation failure must rely on blood transfusions. Over time, the patients' immune systems may launch an attack against the foreign blood.

Using human induced pluripotent stem cells (iPSCs) to grow blood cells reduces the risk of this adverse response because the cells already match the patient's genetic material.

In the Johns Hopkins study, researchers used iPSCs and genome editing to generate gene-corrected cells for use as cell therapy. The scientists had previously devised a way to use iPSCs to create blood cells. However, in patients with sickle cell disease, the lab-grown stem cells would carry the homozygous missense point mutation in the HBB gene encoding adult β-globin proteins associated with sickle cell disease.

To address this problem, the researchers reprogrammed the patients' blood cells into iPSCs capable of making any other cells in the body. These cells can also grow indefinitely in the lab.

The researchers then used CRISPR, a relatively new genetic editing technique, to snip out the gene variant and replace it with a healthy version. The scientists then coaxed the stem into growing into mature blood cells. The stem cells subjected to CRISPR generated blood cells as efficiently as stem cells that were not edited.

This technique of growing blood cells from edited stem cells must become more developed and efficient before it can be medically useful, and researchers will need to test the lab-grown stem cells for safety, but the new approach does offer the possibility of a new treatment option for sickle cell disease.

With further research, techniques involving edited stem cells could help the blood cells of healthy people resist malaria and other infectious agents. While more work needs to be done to create an effective stem cell therapy program for sickle cell disease, this new approach provides great hope for those who suffer from the disease.