Chronic disease is not something unfamiliar to many Americans, especially for those in their older adult years. But at the same time, many suffer from debilitating illnesses much earlier in life. When chronic illness affects one in their teens or young adulthood, their impact is much more profound. This is particularly true for those with sickle cell disease, a blood-related disorder linked to frequent hospitalizations and care. Not only does the condition result in frequent pain crises, but it also leads to organ failure and premature death. To date, the cure for sickle cell disease required both luck and high-risk bone marrow transplants. But now, sickle cell gene therapy could offer new hope to these patients. Within the next year, two new such treatments will be considered for FDA approval. And if approved, this could be a gamechanger in the fight against sickle cell disease.
Understanding Sickle Cell Disease and Its Impact
As noted, sickle cell disease is a hematologic disorder where an individual has an abnormally shaped red blood cell. The shape of a red blood cell resembles that of a crescent or sickle, hence the name of the condition. This disfiguration results from a genetic disease, and because of its related flaw, red cells are more prone to clot. This is especially true when one with the disease is dehydrated, has a fever, or has other vascular problems. The clots that then form result in several pain crises within one’s bones. And over time, patients develop various other problems related to end-organ damage. Strokes and kidney failure are common conditions that occur in sickle cell disease. And because of this, patients with the illness tend to live about two decades shorter than they should.
Certainly, the effects of this disease are profound, which is why a cure for sickle cell disease is needed. This is also the reason pharmaceutical companies have been investigating sickle cell gene therapy as a potential option. Prior to this, the cure for sickle cell disease required a bone marrow transplant. A patient’s bone marrow would be eradicated and replaced with a matching donor’s bone marrow. But finding a donor isn’t easy, and the process required aggressive chemotherapy. As a result, very few patients with sickle cell disease even had this as an option. This contrasts with sickle cell gene therapy, which utilizes a patient’s own stem cells to replace the existing bone marrow. New trials pursuing this approach have shown promise, instilling hope for millions of patients potentially.
It’s worth noting that the vast majority of patients with sickle cell disease are racially Black. As such, social determinants of health have historically played a major role in caring for these individuals. Even though bone marrow transplants represent a cure for sickle cell disease, relatively few actually receive this treatment. In addition, because of the intense bone pain crises that occur, opiates are routinely the treatment of choice. But opiate use has noted stigma, which means these patients often go undertreated. The hope is therefore that sickle cell gene therapy might help reduce social and racial barriers of care. Though this remains to be seen, such treatments will certainly be easier to attain when compared to donor bone marrow transplants.
How Sickle Cell Gene Therapy Works
In many ways, sickle cell gene therapy mimic bone marrow transplant care for sickle cell patients. However, the key thing missing is the necessity of a donor. Instead, bone marrow cells are harvested from a sickle cell patient and then altered to eliminate the defective gene. One company, Vertex Pharmaceuticals, partnered with CRISPR Therapeutics to achieve this process. Using CRISPR gene editing techniques, “normalized” stem cells are returned to the patient’s bone marrow. This then allows the production of normally shaped red blood cells that will not spontaneously clot. Thus, in effect, this reflects a true cure for sickle cell disease patients. Other companies, like Bluebird Bio, are pursuing similar stem cell approaches without using CRISPR. But overall, the end approach is still the same.
Though sickle cell gene therapy is better than bone marrow transplants, these strategies aren’t without risks. Sickle cell gene therapy still requires chemotherapy treatment to rid the bone marrow of its existing sickling stem cells. As a result, risks of infection as well as a number of unpleasant side effects are routinely experienced. This usually requires a month’s long hospitalization, which adds to the cost of these new treatments. Estimates suggest that sickle cell gene therapy will cost about $1 million per patient. Given the severity of symptoms and shortened longevity, this cure for sickle cell disease is worth it for most. But since many are unable to work and Medicaid, it remains to be seen if such a treatment will be covered.
Implementing a Cure for Sickle Cell Disease
Sickle cell gene therapy is an exciting development in the search for a cure for sickle cell disease. However, given the potential social and economic barriers, getting this treatment to the right individuals won’t be without challenges. To highlight this, a current inexpensive medication for sickle cell disease, hydroxyurea, can significantly reduce pain crises. Yet, only about half of all appropriate sickle cell patients receive this drug. Why? Because historically these patients are rarely managed by specialists and instead cared for by primary care providers. In many instances, these providers may not be well versed on sickle cell disease management. If this is the case with an inexpensive medication, then it may be even harder when it comes to sickle cell gene therapy.
At the current time, the FDA will be reviewing clinical data from the two pharmaceutical companies mentioned. It is hoped that within the year, a sickle cell gene therapy will be available to those who qualify. Though it’s still not known precisely whether this represents a full cure long term of not, hope exists. To date, the longest treated patient has had no sickle cell events in over 3 years. Based on this, many researchers are highly optimistic that these new treatments indeed represent a true cure for sickle cell disease.