4 Gene Therapy Techniques for Sickle Cell Disease

4 Gene Therapy Techniques for Sickle Cell Disease

In an interview with HCPLiveTitilope Fasipe, MD, PhD, Assistant Professor, Department of Pediatrics, Texas Children’s Cancer & Hematology Centers, Baylor College of Medicine, spoke about gene therapy and its role as one of the promising areas emerging within the field of sickle cell disease (SCD ).

She’s excited by the clinical trials evaluating the effect gene therapy can have on sickle cell disease as well as the rapidly advancing science that has been producing promising results, so far.

In honor of World Sickle Cell Day, she shared a comprehensive overview of the current status of gene therapy and the techniques being used for sickle cell disease.

The 4 Ways to Fix Sickle Cell Disease

“How do you fix the sickle cell problem?” Fasip asked.

Scientists and researchers have found 4 different approaches to using gene therapy for sickle cell disease and Fasipe shared an overview of each.

1. Producing HbF by Adding Healthy Genes

The first approach she discussed involves introducing a healthy hemoglobin gene to a patient’s body in order for them to begin making their own “good hemoglobin”.

“The reason why we know this can work is because we know that people who are born with a healthy hemoglobin – they have a mutation that helps them make more fetal hemoglobin [hemoglobin F (HgbF)] – they essentially don’t have sickle cell disease, even if they inherit it with sickle cell (so, hemoglobin S plus hemoglobin F).”

2. Mimicking Sickle Cell Trait in Patients with SCD

The next approach incorporates creating a genetic structure similar to sickle cell trait (1 copy of hemoglobin S, HgbS and 1 copy of hemoglobin A, HgbA) in patients with the disease.

Fasipe explained it as an attempt to mimic the effect where a patient ends up having more of a trait phenotype instead of a disease type.

“Giving a healthy hemoglobin or gene addition is one type of gene therapy,” she said.

3. Increasing Fetal Hemoglobin by Correcting the Gene Signal

The third approach Fasipe articulated is called “correction” and has to do with fetal hemoglobin or hemoglobin F. As she mentioned earlier, after birth infants no longer produce hemoglobin F like they did in the womb.

“Another group of scientists is looking at ‘how do we turn that instruction back on, how do we press play again and help us make hemoglobin F?'” She continued, “to do this, you take away the thing that’s blocking the signal , and you can approach this in multiple different ways.”

This is where techniques with CRISPR and RNA silencing come into play.

“That allows you to make hemoglobin F, and again gives you hopefully, not a disease phenotype, but a healthier, almost like a trait phenotype,” Fasipe explained.

4. Out with the Old Hemoglobin, In with the New

The last approach implements the addition of healthy hemoglobin, or the correction of hemoglobin F, but also aims to remove the “bad gene”, hemoglobin S.

“Many of the other steps keep the hemoglobin S there, they just use the healthy hemoglobin to make you healthier,” she stated, “but with this last step, they’re trying to also take away the S while giving you a healthy hemoglobin . So that one, you can imagine is more complicated, but there are scientists working on that as well.”

Many data have been published on the subject, some based on clinical use in humans while some are still in the laboratory beginning to approach use in humans.

“What I say is ‘a complicated disease like sickle cell does require complicated therapy and definitely requires a complicated cure.’ So, these are not easy things and the gene therapy trials have been exciting,” Fasipe said.

Gene Therapy is a Type of Transplant

Generally when a patient needs a bone marrow transplant, they need new bone marrow because theirs has been affected by their disease, whether that’s sickle cell disease or a type of blood cancer leukemia, among others, she explained. The aim of the transplant is to “fix that disease.”

“In today’s world,” she said, “the way we do that is by using somebody else’s bone marrow–so you need a donor.”

The main barrier that comes with a transplant is access to a donor who matches the patient, which is crucial for the patient’s safety and the success of the procedure, according to Fasipe.

The majority of people don’t have a match.

“Gene therapy is trying to find a way to cure you without having to rely on another person that may not match you,” she said.

In terms of those living with sickle cell disease, Fasipe explained that 1 in 10 people have a match in their own family. So, this is not a transplant that has not been available to the majority of patients with sickle cell disease.

She described gene therapy as an “auto-transplant” or a “self-transplant”. A transplant physician takes the patient’s cells, performs the gene therapy technique that corrects the defective genes before the genes are reintroduced to the body.

Gene therapy removes the barrier that comes with finding a donor match.

“It is still a transplant,” Fasipe said, “but instead of getting cells from somebody else, they’re using your own cells that they have now fixed through that gene therapy step.”

While she is a pediatric hematologist and a professor, Fasipe specified that she is not a transplant physician but she works with them very closely. As a result, she’s learned about various techniques that are being explored within the field and is excited to see what the future brings.

“Time will tell which type of gene therapy makes sense for what type of sickle cell patient,” Fasipe explained, “there might be some that work better for one person and another that might work better for another.”

In another segment of this interview, Fasipe discussed what phsycians have learned since gaining access to the newest approved treatments for sickle cell disease.

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