For those who suffer from the blood disorder sickle cell disease, there is really only one cure: a full bone marrow transplant followed by a lifetime of anti-rejection, immune-suppressing drugs. But now, researchers from the National Institutes of Health are testing an attractive alternative for the sickest patients.
Sickle cell disease gets its name from a single genetic change, or mutation, that alters the shape of one’s red blood cells.. Unlike the round cells that can pass easily through the body’s blood vessels, the sickle-shaped cells clump together, clogging up blood vessels. This leads to a lifetime of severe joint pain and, in many cases, organ damage and stroke. In this country it affects primarily African Americans.
The only cure is a bone marrow transplant, in which the patient’s own bone marrow is first depleted with chemotherapy, and replaced by the donor marrow. The patient then faces a lifetime of immunosuppressant, anti-rejection medication to prevent deadly rejection or graft-versus-host disease, a potentially fatal condition where the donor cells attack the recipient’s immune system.
But what if, instead of replacing the entirety of the patient’s bone marrow, doctors only replaced some of it? Would this mix of sickle and non-sickle-shaped cells be enough to reverse the symptoms? A clinical trial published today from the NIH research team in the Journal of the American Medical Association has some encouraging results.
As lead author Dr. Matthew Hsieh noted in today’s press release:
“Typically, stem-cell recipients must take immunosuppressants all their lives. That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen.”
In this study, the researchers performed partial bone marrow transplantations on 30 adults with severe sickle cell disease. After one year, they took 15 patients off the standard regimen of immunosuppressant drugs. And more than three years later, those 15 patients remain free from rejection.
These results are promising, in that a lifetime of immunosuppressants comes with its own set of negative side effects for the patient. According to the paper’s senior author Dr. John Tinsdale:
“Side effects caused by immunosuppressants can endanger patients already weakened by years of organ damage from sickle cell disease. Not having to permanently rely on this medication…means that even older patients and those with severe sickle cell disease may be able to reverse their condition.”
Indeed, the research team found that even a partial transplant—which resulted in a stable mix of both red blood cell types from donor and recipient – was sufficient to reverse the disease’s debilitating symptoms.
The results from this trial open the door to treating patients whose immune systems are already too weak—and are unable to tolerate the negative effects of a full stem cell transplant.
But even this half transplant has the risks associated with donor marrow. That is why CIRM is funding a team using a patient’s own stem cells and genetically modifying them to produce the correct version of the mutated protein. These self-transplants would be safer and open up the therapy to all patients regardless of their ability to find an immunologically matching donor. We expect a clinical trial with this approach to begin soon.
Want to know more about how CIRM-funded scientists are working toward this goal? Check out our “Spotlight on Sickle Cell Disease.”