100 Years But Only One Drug: Sickle Cell Patients Wait For Help

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danger of the procedure for several reasons—in part because the patient’s own cells, not a donor’s, are being transferred back, which theoretically could make for better immune compatibility and less need for harsh drugs.

Another advantage to gene editing or therapy is availability: a patient is his or her own bone marrow donor. In the U.S., sickle cell disproportionately affects African Americans—one in 500 children are born with the disease. The next highest prevalence is in Hispanic Americans, with 1 in 36,000 children born with the disease.

One in 12 black Americans has sickle cell trait, which is an inherited gene from one parent but not the other. Having the ‘trait’ instead of disease doesn’t entirely preclude someone from developing symptoms, however.

For traditional transplants, though, African Americans have a much harder time finding matched donors than any other group.

All in all, it’s estimated that only a few hundred sickle cell patients have had a transplant, and it’s not clear how many of them have succeeded. (A U.S.-funded database shows 353 transplants from 2008 to 2012; survival data is incomplete but shows that patients receiving marrow from unrelated donors have a lower rate of survival.)

Meanwhile, the only approved pharmaceutical for sickle cell is hydroxyurea, a repurposed chemotherapy. It’s useful for relieving the pain episodes, known as crises, and acute chest syndrome, a lung-related complication that can turn deadly.

There are maintenance therapies and ever more sophisticated plans for giving sickle cell patients better lives. For example, one doctor who runs a sickle cell center at a big-city U.S. hospital told me that kids born with either of two genetic variants of the disease get an ultrasound at the age of two. There are four main variants of sickle cell; the two in question are correlated with more strokes. The ultrasound helps predict near-term stroke risk—within the next year—and if the results come back in the danger zone, the child is put on blood transfusions every three to five weeks. (The conversation was on background because the doctor was not cleared by the center to speak to the press.)

Another gene editing program for sickle cell is in the works from Sangamo Biosciences (NASDAQ: SGMO) of Richmond, CA. Sometime in the second half of 2016, Sangamo and its development partner Biogen (NASDAQ: BIIB) will ask FDA permission to start human trials with its program.

To do its gene editing, Sangamo uses a system called zinc finger proteins, which it owns. No one else can use zinc fingers without a license, and Sangamo, with 20 years of development under its belt, is the only company to advance a gene-editing product into human trials, for HIV.

CRISPR/Cas9 hasn’t been around as long as zinc finger proteins, and the technology has a major hurdle to overcome: making sure the molecular “scissors” it uses are making DNA cuts in the right places. Right now, the methods used to detect off-target cuts simply aren’t sophisticated enough. And all it takes is one cut in the wrong place to trigger a tragic unintended consequence. The fear dates back to gene therapy experiments fifteen years ago, in which genes meant to heal kids with severe combined immunodeficiency—the so-called “bubble boy disease”—inserted themselves in the wrong place and triggered cancer. Being more precise with gene editing tools, like CRISPR/Cas9, is still a goal, not a reality.

“Our ability to find off targets isn’t great right now,” says Corn. “No matter how bullish you are, the field [of gene therapy] has been bitten by kids getting leukemia. That should keep everyone in the hematopoietic field up at night.”

(For more on the rollercoaster history of gene therapy, read Ben Fidler’s feature on hemophilia published in March.)

The rapid spread of CRISPR/Cas9—it might not be long before high school students are doing experiments with it—is also keeping people worried for another reason: the potential engineering of human eggs, sperm, and embryos to modify people for aesthetic or social reasons, not medical reasons, and allow those traits to passed on to future generations. There’s also concern that traits engineered into plants and animals meant to spread to entire populations—to create less harmful mosquitoes, for example—could spread out of control.

(My colleagues and I have written about these developments here and here, and Antonio Regalado at Technology Review has done important reporting on the topic. Spurred by papers penned by Doudna, Sangamo CEO Edward Lanphier, and several others, the U.S. National Academy of Sciences and National Academy of Medicine will hold a summit this fall to discuss guidelines on germline editing.)

Curing sickle cell disease should hold no such controversy, of course.

But it holds other cautions. Patient advocate Banks worries that the eventual cost of a product will be out of reach for many U.S. sickle cell patients, 70 percent of whom are low income, she says. If and when that time comes, insurers like … Next Page »

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