A miracle cure for sickle cell disease?

In December, the U.S. Food and Drug Administration approved two gene therapies for sickle cell disease, a life-shortening blood disorder caused by a single mutated gene.

The therapies have all the symptoms of miracle cures. They halt the mutation that deforms red blood cells, which results in inflammation and organ damage. They eliminate the need for daily medications. They bypass a hurdle of bone marrow transplants, which require hard-to-find donor matches.

“This is a dream come true,” says Martin Safo, Ph.D., a professor at the VCU School of Pharmacy who has researched sickle cell disease for three decades. “When I started, my mentor and I, this is all we talked about — that one day there’s going to be a gene therapy to treat this disease. 

“But the question is the impact. Will this help millions of sickle cell patients all over the world? And my answer is: The impact is going to be minimal for the foreseeable future.”

The new therapies — Casgevy (which uses CRISPR, a gene editing tool, to alter DNA) and Lyfgenia (which adds a good hemoglobin gene to a patient’s DNA) — offer hope for the 100,000 Americans living with sickle cell disease. But for most, hope is all they currently offer.

These marvels of medical science cost millions and are procedurally arduous. Only a few dozen medical centers are authorized to provide them.

“It’s a transformative therapy,” says Wally Smith, M.D., director of VCU’s adult sickle cell program. “But we will have to screen 1,200 adults to get, I’m guessing, 15 to 20 patients who get it.”

The therapies work by extracting blood stem cells — the cells from which all others “stem” — out of bone marrow, then engineering around the sickle cell mutation. The stem cells are reimplanted after the patient undergoes chemotherapy, which destroys the diseased blood cells and allows the rehabbed stem cells to produce healthy cells in their place.

The few centers that can do this (including VCU, which is a Lyfgenia trial site) will only be able to treat a handful of patients to start, Smith says. The monthslong procedures require extended hospital stays. They don’t repair the organ damage or chronic pain a patient might already have.

“For some, I think the hard reality would be ‘I already have such bad organ damage, and I’m 50. Is it worth risking my life urgently with chemo in order to try to stop the damage from progressing? Or should I live out the rest of my years, use [daily medication] and do the best I can?’” Smith says.

“I think if I were in that situation, I’d think long and hard before I said yes.”

But back to that hope. Even though the new therapies are out of reach for many, it might not always be that way.

The aforementioned bone marrow transplant also involves collecting and infusing stem cells. It was a mid-20th century creation that won its performing physician a Nobel Prize. Today, more than 9,000 such transplants are performed in the U.S. annually, according to data from the U.S. Health Resources and Services Administration.

The patient pool will also undoubtedly increase, says Beth Krieger, M.D. (H.S.’20), who specializes in cellular therapies at Children’s Hospital of Richmond at VCU. The FDA estimates 20,000 Americans — those who are 12 and older and experience repeated pain — are currently eligible for the therapies. But they are also being tested in younger children.

With early treatment, they could be spared sickle cell’s worst effects, Kreiger says. U.S. patients typically live only to their early 50s, and more than half are insured through Medicaid, according to the Centers for Medicare and Medicaid Services. Those with private insurance spend an average of $1.7 million in their lifetimes on medications, according to the American Society of Hematology.

We spoke with Krieger, Safo and Smith about these dream treatments, their possibilities and limitations. Their quotes have been lightly edited for length and clarity.