Gene therapy used on sickle-cell anemia

CINCINNATI (AP) — After a decade of research, Cincinnati Children’s Hospital Medical Center researchers hope they’ve discovered a way to use gene therapy to cure sickle-cell disease.

They hope federal regulators will sign off on the procedure and clear the way for human testing to begin next year.

Using lab animals and human tissue samples, scientists led by Punam Malik have developed a cutting-edge gene therapy that made the body stop producing the malformed red blood cells that characterize sickle-cell disease.

“If it works, it’s a cure,” said Malik, a hematology-oncology specialist who leads all of the gene and molecular therapy research at Cincinnati Children’s.

Sickle-cell anemia affects 70,000 to 100,000 people in the United States. People with sickle-cell disease face a lifetime of pain and fatigue and risk stroke, blindness, organ failure and bone loss.

A genetic defect makes red blood cells carry an abnormal type of hemoglobin — called hemoglobin S — that changes their shape and makes it harder for the blood cells to pass through blood vessels. Tissues, including organs, become damaged when these red blood cells can’t efficiently carry oxygen to them.

One study found that organ failure killed about 20 percent of adult sickle-cell patients.

Malik and her colleagues’ therapy would implant a gene that counteracts hemoglobin S, allowing patients to make the correct type of hemoglobin to form normal red-blood cells that efficiently carry oxygen to tissues.

If the proposed clinical trial under review by the federal government is approved, researchers will collect bone marrow stem cells from patient volunteers. In the lab, they’ll implant engineered viruses containing a new gene in those stem cells, which make red blood cells. They’ll then return the stem cells containing the engineered viruses to the patient volunteers’ bodies.

Malik hopes the implanted gene would allow sickle-cell patients to make hemoglobin F, which lets red blood cells form normally.

If the therapy works, the engineered virus would continue to reproduce in volunteers’ bone marrow and enable them to permanently make normal red blood cells.

If the trial is approved, it could take five years or longer, as regulators and researchers monitor volunteers to make sure it’s safe and determine whether it works.

The experimental therapy might not work in humans, as sometimes success doesn’t translate from tests on mice, Malik said.

But researchers are especially hopeful because of the impact of the disease and the fact that treatment options are limited.

Bone-marrow transplants are effective, but only about 10 percent of people with sickle-cell disease get them because it’s hard to find a donor who matches. And they must usually be done before the age of 16 or 17 to make the risks worthwhile.

A drug called hydroxyurea lets the body make hemoglobin F and reduces the number of sickle cells but doesn’t remove them completely. It also has side effects, including immune suppression.