Several dozen patients with sickle cell disease will be among the first in the United States treated for a genetic disease with the experimental gene-editing technology CRISPR.
“This is an extraordinary time” in the treatment of sickle cell disease, said Dr. Alexis Thompson, hematology section head at the Ann and Robert H. Lurie Children’s Hospital of Chicago, who is not involved in the trial. “It’s terribly exciting that there is so much attention on cutting-edge science and a condition that has lagged far behind many other medically important diseases.”
The study aims to recruit up to 45 adults with severe sickle cell disease. Thompson said that many in the scientific community have been looking forward to the trial since it was posted in late 2018, though only Monday was a patient publicly identified in an interview with NPR.
A representative for Vertex Pharmaceuticals, a co-sponsor of the CRISPR trial, declined CNN’s request for an interview with an expert involved in the trial. The company did not disclose how far along the trial is but confirmed that it’s still enrolling patients. Another co-sponsor, CRISPR Therapeutics, also declined to comment.
People with sickle cell disease, a group of inherited blood disorders, have abnormal hemoglobin in red blood cells that can cause them to get “hard and sticky,” clogging blood flow in small vessels, according to the US Centers for Disease Control and Prevention. Hemoglobin is a protein found in red blood cells that is responsible for carrying oxygen throughout the body.
Approximately 100,000 Americans, most of African ancestry or identifying as black, are affected by the disease, which can result in pain, anemia, blindness, organ damage and a shorter average lifespan overall.
In the CRISPR trial, doctors aim to increase the production of a different kind of hemoglobin: fetal hemoglobin, which makes it harder for cells to sickle and stick together.
This process involves removing premature cells from the bone marrow and modifying them – using CRISPR in the lab – to eventually produce fetal hemoglobin. After a round of chemo, these cells are given back to the patient, replacing cells that were there.
With more fetal hemoglobin, patients might be able to avoid some of the complications of sickle cell disease, according to Dr. Jane Little, director of the sickle cell program and professor of medicine at the University of North Carolina at Chapel Hill, who is not involved with the new trial.
“Organ damage could potentially slow,” she said.
A versatile tool
A single-dose CRISPR treatment is not the only possibility for patients with sickle cell disease. “There may be more than one curative option,” said Thompson, who is also a professor of pediatrics at Northwestern University’s Feinberg School of Medicine.
Thompson referred to other gene-editing technology called zinc-finger nucleases, which are also being investigated as a way to spur production of fetal hemoglobin.
A teen with sickle cell disease achieved complete remission using another method of gene editing, a lentivirus, at a children’s hospital in Paris. Instead of focusing on fetal hemoglobin, this patient received an “antisickling” gene to replace the one that causes the disease.
Thompson said eyes are on gene-editing therapies because many people “who have conditions like sickle cell disease could be cured by a bone marrow transplant, but most of us will not have a suitable matched donor to provide the bone marrow.”
Using gene editing, the patient becomes their own donor.
CRISPR is also being investigated to treat beta thalassemia, an inherited blood disorder in which the body doesn’t make enough hemoglobin.
“Sickle cell and beta thalassemia have different mutations,” said Dr. Vivien Sheehan, assistant professor of pediatrics and hematology at the Baylor College of Medicine, who is not involved with the trial. An advantage of CRISPR is that “you can fix many different diseases.”
Another trial is recruiting patients who have a genetic eye disorder, injecting a CRISPR treatment just beneath the retina in an effort to prevent vision loss. In this trial, cells aren’t removed and sent to a lab; the gene editing occurs in the body itself.
Weighing risks and benefits
Sickle cell patients in the CRISPR trial still have to make room in the bone marrow for the newly edited cells, Little said. The chemotherapy that follows carries its own risks and potential side effects, like loss of fertility and myelodysplastic syndrome, a type of blood cell cancer.
And with gene editing, there’s also the unlikely possibility of altering the wrong gene or cutting out more than necessary, Little added.
Still, it remains to be seen how any potential “curative or corrective” therapies for sickle cell disease will compare with other drugs that treat the condition, including a handful that could seek US Food and Drug Administration approval within the next year or so, Thompson said. Among the treatments currently used is a medication called hydroxyurea, which can stimulate the production of fetal hemoglobin.
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“We are going to need, at some point, to be able to measure these to say which ones of these was better,” Thompson said, “and are there subsets of patients for which one of these is superior?”
Experts say it’s too early to tell how the CRISPR patients will fare long-term – what sort of improvement researchers see versus the risks they bear with gene-editing technology and chemotherapy.
“We don’t really know how much fetal hemoglobin we need to treat a patient,” Sheehan said. That’s why it’s hard to know so early whether the edited cells from CRISPR will actually be effective.
“What kind of blood are we making now that we’ve undergone this editing process?” Sheehan asked. “The question is: Is this a cure?”
CNN’s Susan Scutti contributed to this report.