Jeffrey Glassberg, MD, MA
Assistant Professor of Emergency Medicine, Hematology and Medical Oncology
Associate Director of The Mount Sinai Comprehensive Sickle Cell Program
Icahn School of Medicine at Mount Sinai
Hardships, and New Hope, for Sickle Cell Patients
Sickle cell disease affects about 100,000 people in the United States, most of them African Americans. Over the last four decades, the average life expectancy for patients has jumped from age 14 to the 50s and higher, thanks mainly to newborn screening programs, preventive care, and antibiotic treatments to prevent associated infections, along with assistance from hydroxyurea, a drug approved in 1998.
Now, promising new treatments are on the horizon for this chronic disease, which, though not immediately fatal, can cause complications that dramatically affect patients' day-to-day lives.
What Is It?
Sickle cell disease is an inherited blood disease caused by a mutation in the hemoglobin gene. Hemoglobin is the molecule in blood that carries oxygen. In people with sickle cell disease, the hemoglobin sticks to itself, causing red blood cells to form a C-like shape that looks like a farmer's sickle. Red cells break down faster in people with sickle cell disease and the cells become sticky, causing them to get stuck on their way to delivering oxygen throughout the body. This can block blood flow and cause complications in any part of the body.
Pain and Complications
The disease's main symptom is random, excruciating pain. This pain is usually felt in areas with a lot of bone marrow, like the legs, lower back, and buttocks. In addition, other substances can back up behind the blood, causing engorgement, which is also painful.
Insufficient oxygen delivery can also cause strokes, bone tissue death, and problems with the eyes, skin, gallbladder, or any other organ, as well as increased susceptibility to infections.
Hydroxyurea, the only drug approved by the Food and Drug Administration for sickle cell disease, makes blood cells function more normally, reducing pain and helping organs work better.
Unfortunately, for various reasons like fertility concerns and patients' fears about potential side effects, less than half of the people with sickle cell disease are taking it.
A handful of new drugs have progressed to phase 3 clinical trials, during which medications are studied in hundreds of people to confirm their effectiveness, monitor side effects, and collect safety information.
One of the most exciting drugs is a "selectin inhibitor" called rivipansel (GMI-1070), which improves blood flow during a pain crisis by blocking the molecules that make cells stick to blood vessels. Early data indicate this medicine helps patients through crises faster and with a lot less pain. Another drug, known as Aes-103, prevents the hemoglobin from staying stuck, offering less opportunity for damage to the inside of the cell. Though these drugs seem to work, it could be months or years before they hit the market.
Bone Marrow Transplant
Even with the best care, some people still experience excruciating pain, which prevents them from functioning and can lead to continual visits to the emergency room. These patients may have the option of a bone marrow transplant, which can cure sickle cell disease but is limited to those who have a matched marrow donor.
A transplant comes with steep risks. About 1 percent of patients die from the procedure, which involves high doses of toxic chemotherapy. And to help the body accept the "foreign" donor cells, patients have to take medications, sometimes for life, to suppress their immune systems. This increases the risk of life-threatening infections.
In a promising new type of bone marrow transplant, the marrow comes from the patient's own bones rather than from someone else's. Samples of the patient's bone marrow are taken to the laboratory, where, through gene therapy, nanoparticles derived from viruses are used to find defective hemoglobin genes and replace them with normal ones. Doctors change the DNA of as many cells as possible, creating a group of cells that no longer have the mutation. The doctors then wipe out the patient's original bone marrow and replace it with the corrected marrow. Because the transplanted bone marrow is the patient's own, no immunosuppressant drugs are necessary.
This novel treatment is now being studied in a small clinical trial led by the National Institutes of Health. Researchers are working very slowly and carefully, taking every precaution to make sure the procedure is safe for each patient involved. It will probably take a few more years before the next trial phase. However, the initial data are very promising; people in the trials started to make their own sickle cell-free blood and did so for more than year with this gene therapy.
Helping Patients Manage
Sickle cell patients face many hardships, like intense pain attacks that require high doses of medicine, frequent infections, and a slow decline in organ function. That's why it is important to make sure people get the common therapies we already know work, like hydroxyurea, routine medical care and screening, and health maintenance.
Most hematologists (doctors who specialize in blood disorders) have limited experience caring for people with sickle cell disease, so if you have the disease, try to see a hematologist who treats a large number of patients with it. This will help you get the best care possible, and you will also be poised to receive new therapies as they come out in the future.