Experimental CRISPR Treatment For Sickle Cell Disease Appears Effective : Shots

Like millions of other Americans, Victoria Gray has been sheltering at home with her children as the U.S. struggles through a deadly pandemic, and as protests over police violence have erupted across the country.

But Gray is not like any other American. She’s the first person with a genetic disorder to get treated in the United States with the revolutionary gene-editing technique called CRISPR.

And as the one-year anniversary of her landmark treatment approaches, Gray has just received very good news: The billions of genetically modified cells doctors infused into her body clearly appear to be alleviating virtually all the complications of her disorder, sickle cell disease.

“It’s wonderful. It’s the change I’ve been waiting on my whole life,” Gray tells NPR, which has had exclusive access to chronicle Gray’s experience over the past year.

Sickle cell disease, a rare blood disorder that disproportionately affects African-Americans in the U.S., can be very difficult to treat effectively.

The last time NPR spoke with Gray — in November — her doctors had just gotten the first hints the treatment might be working. Now, after nine months of careful testing, the treatment shows no signs of waning, making her doctors more confident that ever the experiment has been a success.

“It’s hard to put into words the joy that I feel — being grateful for a change this big. It’s been amazing,” says Gray, 34, who lives in Forest, Miss.

In many ways, it’s a change that came just in time, Gray says. In the fall, the National Guard deployed her husband to Washington. And then, the coronavirus pandemic triggered a national lock down. Gray was suddenly home alone with three of her kids.

Her great aunt as well as the pastor of her childhood church died of COVID-19. Friends at her current church have been getting sick.

If she hadn’t had the treatment, Gray says she doesn’t know how she’d be coping. She would have been too weak to care for her children, and probably would have been hospitalized at a time when hospitals feel especially unsafe.

“Since my treatment I’ve been able to do everything for myself, everything for my kids. And so it’s been joy not only for me but for the people around me that’s in my life,” she says.

The promise of a cure

The researchers conducting the study Gray started caution that it’s too soon to reach any firm conclusions about the long-term safety and effectiveness of the approach. Gray is just one patient who has been followed for what is still a relatively short period of time, they note.

But Gray’s experience so far, along with two other patients who received the same treatment for a similar disorder, indicate the therapy has been effective for her, and may work for other patients as well, they say.

“To have it work in this way is extremely thrilling to see and extremely exciting,” says Dr. Haydar Frangoul of the Sarah Cannon Research Institute in Nashville, Tenn., who is treating Gray.

At a meeting of the European Hematology Association on June 12, Frangoul and other researchers presented the latest results of their latest testing of Gray as well as the two study subjects with a related condition, beta thalassemia, who also appear to be benefiting.

“It’s very exciting,” says Dr. David Altshuler, the chief scientific officer at Vertex Pharmaceuticals in Boston, which is developing the treatment with CRISPR Therapeutics in Cambridge, Mass. “Patients and families have been waiting a very long time for a highly effective therapy.”

The companies also revealed that a second sickle cell patient had been treated as part of their research program, along with three other beta thalassemia patients.

The promising results are also encouraging other doctors and researchers, who hope CRISPR may also lead to new treatments for many diseases. Studies have already tested CRISPR to treat cancer and a rare genetic condition that causes blindness. CRISPR enables scientists to make changes in DNA much more easily than ever before.

“I think this is a huge leap for the medical field,” Frangoul told NPR in an interview

How the treatment works

Sickle cell disease is caused by a genetic mutation that produces a defective form of hemoglobin, a protein needed by red blood cells to nourish the body with oxygen. The defective hemoglobin turns red blood cells into deformed, sickle-shaped cells that get jammed inside blood vessels, causing excruciating attacks of pain, organ damage and often premature death.

“Before the treatment, it would be so bad it would be crippling,” says Gray of her pain crises.

For the experimental treatment, scientists remove cells from patients’ bone marrow and use CRISPR to edit a gene, which enables the cells to produce a protein known as fetal hemoglobin. Fetal hemoglobin is made by fetuses in the womb to get oxygen from their mothers’ blood, but usually stops being produced shortly after birth.

The hope was that restoring production of fetal hemoglobin would compensate for the defective hemoglobin produced by sickle cell patients. Beta thalassemia patients don’t have enough hemoglobin.

Scientists had hoped that after the treatment, which Gray received July 2, 2019, at least 20% of the hemoglobin in Gray’s system would be fetal hemoglobin.

Blood tests so far have shown the levels far exceeded that. About 46% of the hemoglobin in Gray’s system continues to be fetal hemoglobin, the researchers reported. In addition, fetal hemoglobin has remained present in 99.7% of her red blood cells, they reported.

Another promising finding is that a biopsy of Gray’s bone marrow cells found more than 81% of the cells contained the intended genetic change needed to produce fetal hemoglobin, indicating the edited cells were continue to survive and function in her body for a sustained period.

The researchers also reported that the first patient to receive the same treatment for beta thalassemia in Germany has now been able to live without blood transfusions for 15 months. Previously, the researchers had reported data for that patient for nine months. In addition, four other beta thalassemia patients have been treated, including one who has been transfusion-free for five months, the researchers reported.

While Gray and the beta thalassemia patients experienced some health complications following their procedures, none appear to have been due to the gene-edited cells and all recovered, according to the researchers.

‘A huge change’

Perhaps most importantly, the changes appear to have translated into significant health benefits for Gray. She hasn’t had any severe pain attacks since the treatment and hasn’t required any emergency room treatments, hospitalizations or blood transfusions.

In each of the previous two years, Gray had required an average of seven hospitalizations and emergency room visits due to severe pain episodes as well as requiring regular blood transfusions. She has also been able to significantly reduce her need for powerful narcotics to alleviate her pain.

“It’s a very big deal for me,” Gray says. “It’s a huge change.”

“Now I’ll be there to help my daughters pick out their wedding dresses. And we’ll be able to take family vacations,” she says. “And they’ll have their mom every step of the way.”

And Gray hopes her story will give other people hope too.

“We need this right now more than ever, you know? It’s a blessing,” she says. “It gave me hope when I was losing it. So I feel joy, you know, knowing that there is hope.”