On the Cusp of a Cure - Sickle Cell Disease

After 30 years of research, one surgeon is close to a breakthrough for sickle cell disease.

It’s a good rule of thumb that when it comes to sick kids, the sooner a problem is identified and treated, the better the prognosis. Many of CHOP’s patients are toddlers, infants or even newborns. But one group of surgeons and researchers at CHOP works on a whole different timeline: They treat babies before they are even born.

In 1981, surgeon Alan Flake, MD, was part of the very first open operation on a fetus still in the womb. Today, Flake is not only one of the world’s top fetal surgeons, but he is also director of the Center for Fetal Research at CHOP. There he has spent most of his 30 years in the field working on what could be one of the biggest medical breakthroughs in a generation: a cure for sickle cell disease.

Sickle cell disease affects millions of people worldwide and is the most common inherited disorder in African Americans, of whom 1 in 375 is born with the disease. Instead of the normal soft, red blood cells that most of us have, people with the disease have stiff, sickle-shaped cells that clump and block blood vessels, leading to a host of problems from debilitating pain crises and fatigue to potentially fatal heart attacks and strokes. Sickle cell patients are commonly hospitalized three or four times a year — every fever means straight to the Emergency Department. Heartbreakingly, most people with the disease will succumb to it before their 50th birthday.

Although bone marrow transplants can cure sickle cell disease, the procedure is so risky that it’s usually considered worse than the disease. What Flake is developing could be a true cure — a way for children to be treated before birth and grow up completely symptom-free.

Because red blood cells are made in bone marrow, the procedure involves transplanting stem cells from the mother’s bone marrow to the child. The first transplant is done during a special window in early pregnancy when the fetus’ immune system is not yet fully developed; at this stage, the fetus’ body tolerates its mother’s cells as if they are its own, avoiding the toxic chemotherapy typically required by bone marrow transplantation. After the baby is born, a second transplant cements the process. He or she will be able to produce normal red blood cells, without any symptoms of sickle cell disease.

The procedure is so advanced that Flake is even helping design the instruments needed to do it, including a narrow needle to inject cells into the fetus in a minimally invasive way. He plans to enter clinical trials for the procedure within three years and sees the potential for it to cure a broad range of related disorders, including thalassemias.

Since 2007, the Albert M. Greenfield Foundation has been a major supporter of Flake’s work, but the doctor’s team still needs significant funding to make this pioneering research a clinical reality. To that end, CHOP Foundation created Hope on the Horizon, a volunteer-driven campaign working to raise those critical funds through private philanthropy. Together we can make a big difference for children with this devastating disease.

From the latest issue of Children’s View.