4 gene therapy techniques for sickle cell disease


In an interview with HCP LiveTitilope 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 emerging promising areas in the field of sickle cell disease (SCD).

She is excited about the clinical trials evaluating the effect gene therapy can have on sickle cell disease as well as the rapid advances in science that have so far produced promising results.

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

The 4 Ways to Fix Sickle Cell Disease

“How do you solve the problem of sickle cell disease? Fasip asked.

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

1. Produce HbF by adding healthy genes

The first approach she talked about is introducing a healthy hemoglobin gene into a patient’s body so they can start making their own “good hemoglobin.”

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

2. Imitation of sickle cell trait in patients with SCD

The next approach is to create a genetic structure similar to the 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 than one trait phenotype instead of one disease type.

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

3. Increase fetal hemoglobin by correcting genetic signal

The third approach articulated by Fasipe is called “correction” and relates to fetal hemoglobin or hemoglobin F. As she mentioned earlier, after birth, infants no longer produce hemoglobin F as they did in the womb. ‘uterus.

“Another group of scientists are 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 remove the thing that’s blocking the signal, and you can approach that in a number of different ways.”

This is where techniques with CRISPR and RNA silencing come in.

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

4. Forget the old hemoglobin, make way for 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.

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

A lot of data has been published on the subject, some based on clinical use in humans while others are still in the lab and beginning to approach human use.

“What I’m saying is ‘a complicated disease like sickle cell disease needs complicated therapy and certainly needs complicated treatment.’ So it’s not easy stuff and the gene therapy trials have been exciting,” Fasipe said. .

Gene therapy is a type of transplant

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

“In today’s world,” she said, “the way we do it is to use someone else’s bone marrow – so you need a donor.”

The main hurdle that comes with a transplant is access to a matched donor, which is crucial for patient safety and the success of the procedure, according to Fasipe.

The majority of people don’t have a match.

“Gene therapy tries to find a way to cure you without having to depend on another person who may not be your match,” she said.

When it comes to people living with sickle cell disease, Fasipe explained that one in 10 people have a match in their own family. So it’s not a transplant that hasn’t been available to the majority of sickle cell patients.

She described gene therapy as “auto-grafting” or “auto-grafting”. A transplant doctor takes the cells from the patient, performs the gene therapy technique which corrects the faulty genes before the genes are put back into the body.

Gene therapy removes the hurdle that accompanies finding a matched donor.

“It’s still a transplant,” Fasipe said, “but instead of getting cells from someone else, they’re using your own cells that they’ve now fixed through this therapy step. genetic.”

While she is a pediatric hematologist and professor, Fasipe clarified that she is not a transplant doctor but works closely with them. As a result, she has learned various techniques that are being explored in the field and is excited to see what the future holds for her.

“Time will tell which type of gene therapy makes sense for which 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 doctors have learned since gaining access to the latest approved treatments for sickle cell disease.


Comments are closed.