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A New Clinical Trial Will Explore Gene Editing For Sickle Cell Disease

 Conceptual paper illustration of human hands and DNA in a lab.

Eugene Mymrin / Getty Images

Key Takeaways

  • The U.S. Food and Drug Administration authorized a trial that aims to correct the defect that causes sickle cell disease by using CRISPR technology.
  • The trial is scheduled to take place for four years.
  • Current commonly used therapies for sickle cell disease include oral medications, transfusions, and stem cell transplants.

Last month, the U.S. Food and Drug Administration (FDA) authorized the first-in-human clinical trial of gene-editing technology, CRISPR-Cas9, in patients with sickle cell disease using the patient’s own blood-forming stem cells.

Patients with sickle cell disease have a mutation in their beta-hemoglobin gene, which leads to the production of red blood cells that rupture and form a sickle shape, causing them to have trouble passing through small blood vessels in the body. This in turn blocks the flow of blood and can lead to severe pain and serious complications.

Currently, the only cure involves a stem cell transplant from a donor, but in this new clinical trial, CRISPR gene editing will replace the mutated genes with healthy versions using the patient's own stem cells.

The clinical trial will be jointly conducted by a University of California Consortium, made up of researchers from the University of California, San Francisco, University of California, Berkeley, and University of California, Los Angeles.

This study will last for four years, and will include nine patients who have severe sickle cell disease, consisting of six adults and three adolescents, in Los Angeles and Oakland, California.

What Is Sickle Cell Disease?

Sickle cell disease is an inherited condition, where most do not show signs until they are around six months old. There is a wide range of symptoms that people with sickle cell disease may experience, including chronic pain, effects of anemia, and swelling of the hands and/or feet.

It's estimated that the condition occurs in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans. "The history of sickle cell disease has been intertwined with the history of racism and discrimination," Enrico Novelli, MD, MS, the director of the UPMC Adult Sickle Cell Disease Program, tells Verywell. "Sickle cell disease predominantly, although not exclusively, affects African Americans. The disease has also been neglected, particularly by big pharma, for a long time."

Current Treatment for Sickle Cell Disease

There are multiple treatments currently used to help people with sickle cell disease manage their condition, in addition to therapies undergoing clinical trials like CRISPR. According to the National Heart, Lung, and Blood Institute, the treatments fall into the three categories:

  • Medications
  • Transfusions
  • Blood and bone marrow transplant (or stem cell transplant), which is the only cure for sickle cell disease right now

Umut A. Gurkan, PhD, the Warren E. Rupp Associate Professor at Case Western Reserve University, tells Verywell that medication treatment options for sickle cell disease had been fairly limited for decades. "The best available therapy for sickle cell disease was a drug known as hydroxyurea, which was originally designed as a cancer drug, [that] was repurposed for sickle cell disease [...], it was actually quite frustrating for many patients and for many researchers as well," he says. In 2019, the FDA approved new medications voxelotor and crizanlizumab-tmca to help manage sickle cell disease specifically.

Currently, the only cure for the disease is a stem cell transplant. However, complications like graft-versus-host disease, which causes the new immune system cells may attack certain organs in the recipient of the transplant, can occur.

"Stem cell transplant still remains a relatively affordable and relatively safe curative treatment," Novelli says. "As we move forward with gene therapy approaches we should not forget that stem cell transplant continues to remain an excellent option."

As new therapies for sickle cell disease are developed, Gurkan, who conducts research for the Cure Sickle Cell Initiative, emphasized that it is important for patients, their families, and caregivers to be on board for any new treatment. "Everybody should be onboard for these therapies to work, and we should all be on the same page in understanding the real needs the challenges and then tackle them together," Gurkan says.

What This Means For You

There are currently many research efforts aimed at helping cure and better treat sickle cell disease. While gene-editing technology like CRISPR isn't currently available as a treatment, it may become part of a potential treatment option in just a few years.

CRISPR Sickle Cell Disease Clinical Trial

Previous trials have attempted to use CRISPR to help treat sickle cell disease, but according to Mark Walters, MD, a professor of pediatrics at UCSF and principal investigator of the clinical trial and gene editing project, the UC Consortium's trial "is unique in that it targets the sickle mutation directly, and uses a short piece of DNA as the healthy template to build a new healthy sickle disease."

A January 2021 study published in the New England Journal of Medicine previously indicated that using CRISPR to raise the fetal hemoglobin levels in red blood cells to treat sickle cell disease may be helpful. "That's not really the same as correcting the mutation because the sickle mutation is still present in those red blood cells, it's just that its level is suppressed by the fetal hemoglobin that's made," Walters tells Verywell.

Walters also believes that CRISPR may be able to get rid of some of those complications associated with current therapies for sickle cell disease. "Because the CRISPR technology that we're developing uses a person's own cells, there's no there's absolutely no risk of graft-versus-host disease because the two immune systems will be the same," he says.

The people with severe sickle cell disease participating in the UC Consortium's trial were also selected because they did not respond well to available therapies.

"To begin a new therapy for which we don't have any safety or effectiveness information, typically what we do is target older individuals adults who've had a lot of trouble with their sickle cell disease, a lot of health issues, despite having had or had access to the best supportive care that's available, short of doing a bone marrow transplant," Walters says. If the trial is considered to show safe and promising results, Walters says "then we'll begin to offer it to younger patients who might have milder symptoms of the disease."

The Importance of Affordable Treatment

Treatment for rare diseases like sickle cell disease can be expensive for people with this condition and their families, even though significant jumps in research have been made. Traveling to and from hospitals to get treatment may also place a financial burden on patients. This new CRISPR clinical trial may be similarly inaccessible if made available to the public in the future.

While CRISPR and other therapies for sickle cell disease are costly right now, Walters hopes that ongoing research will make CRISPR gene correcting therapies more affordable.

"Right now we do that correction of the cells outside the body, but there are new technologies ... that might allow us to deliver those same tools through an injection into the bloodstream," he says. "Then those tools would find the blood-producing cells in the bone marrow where they normally reside, make the correction, and then those stem cells would then begin to produce healthy red blood cells."

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  1. University of California, San Francisco. UC Consortium Launches First Clinical Trial Using CRISPR to Correct Gene Defect That Causes Sickle Cell Disease. March 30, 2021

  2. National Heart, Lung, and Blood Institute. Sickle Cell Disease. Updated September, 1 2020

  3. MedlinePlus. Sickle Cell Disease. Updated: August 18, 2020

  4. Hsieh M, Fitzhugh C, Weitzel R et al. Nonmyeloablative HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Phenotype. JAMA. 2014;312(1):48. doi:10.1001/jama.2014.7192

  5. Frangoul H, Altshuler D, Cappellini M et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. New England Journal of Medicine. 2021;384(3):252-260. doi:10.1056/nejmoa2031054