Stories of Hope - Sickle Cell Disease

Spotlight on Sickle Cell Disease

On May 4, 2011 the CIRM governing board heard a Spotlight on Sickle Cell Disease featuring reseachers, clinicians and a patient speaking about their hope for stem cell research. These are their stories.

Nancy Rene - sickle cell disease advocate

Nancy Rene
Los Angeles, CA

For the first nine months of Joseph Katambwe's life, everything was perfect. Then one day he started crying and could not stop.

"He could not be comforted," said his grandmother Nancy Rene. It was his first brush with the ailment he was diagnosed with before birth, sickle cell disease. His father, whose younger brother also had sickle cell, recognized the signs, and the parents rushed their baby to the hospital. When Rene saw the baby later that day, he was still crying and slapping at the oxygen tube in his nose.

"I remember the tubing, and he hit it with both hands. He didn't like it. The next day, he hit it with only one hand. He would cry, and only his left side was moving." By that night it was confirmed, Joseph had suffered a stroke.

Nine years later, Joseph's right side is still a little weak, and the 9-year-old wears a leg brace on that side. But, Rene says, "Being a little boy trumps having a stroke."

"He runs as fast as other kids; he rides his two-wheeler," she says. And every six weeks, he goes in for a blood transfusion. "He really does not cry. He understands this is thing in life."

Bone marrow transplants have cured sickle-cell patients with matching donors. "That's a wonderful thing," Rene says. She looks forward to a day when stem cell treatments will be possible in children without a matching donor – work now under way in the lab.

"This research is something that can really make difference in the lives of kids and families and I certainly cannot thank you enough for making it happen," she says.

TOWARD A CURE: SICKLE CELL DISEASE

Red blood cells are flexible, malleable discs that squeeze through the tiniest of capillaries, ferrying their oxygen payload to all tissues of the body. But an inherited genetic error in a pair of hemoglobin genes distorts the cells into inflexible crescents and sickle shapes. In low oxygen conditions, these inflexible cells careen into rush-hour pile-ups in those tiny blood vessels, blocking blood flow. The result is pain, organ damage and stroke, the effects of sickle cell anemia.

Healthy red blood cells are filled with free-floating hemoglobin molecules—the protein that carries oxygen. But in sickle cell disease, the proteins no longer float freely, but instead stick to one another, tangling into rope-like cords that distort the shape of the cell and hinder its flexibility.

One approach to curing sickle cell disease is to replace the flawed blood-forming stem cells with stem cells lacking the error, a method used successfully some 250 to 300 times in the United States. In those instances, the patients received stem cells from donors who were a close genetic match. But finding a match for each of the 80,000 Americans with sickle cell disease is an impossible task. That's why Donald Kohn, M.D., director of the UCLA Human Gene Medicine Program, and colleagues, are working on ways to repair the sickle cell patient's own stem cells and then return them. He has a $9 million disease team award from CIRM to do just that.

The researchers plan to collect the sickle cell patient's blood-forming stem cells, which live in bone marrow, and, in a laboratory, modify the cells to include a normal copy of the hemoglobin gene. With this engineering accomplished, physicians would employ chemotherapy to destroy the patient's bone marrow. Finally, the medical team would return the corrected cells to the patient and those corrected cells would replenish the patient’s blood supply with healthy red blood cells.

In mouse experiments, they can induce 15 percent to 20 percent of all blood-forming stem cells to make the corrected gene. In humans this is the bare minimum of what is needed. Mice who received the altered genes did not develop kidney problems, while similar mice without the genetic correction did, Kohn says.

Kohn is on track to take this approach to treat patients with sickle cell disease into clinical trials within four years. "This is the best I've ever had a project work in my lab in 25 years," Kohn says.

"Here is an opportunity for a cure," says Bertram Lubin, MD, CIRM governing board member and president of the Children's Hospital and Research Center in Oakland, a leader in the fight against sickle cell disease. "This approach overcomes many of the problems we have with bone marrow transplant."