The Brink of Scientific History – The First Gene Editing Therapy Nears FDA-Approval for Sickle Cell Disease That Causes Debilitating Pain

Earlier this Fall, the FDA met with an advisory committee of experts who recommended a new promising treatment for the painful disease. The treatment is known as “exa-cel,” which is short for exagamglogene autotemcel. It uses a gene-editing technique called CRISPR, which is shorthand for clustered, regularly interspaced short palindromic repeats. CRISPR is a revolutionary gene editing method that allows researchers to alter DNA sequences and modify gene function easily.

The FDA will evaluate the research behind CRISPR and how safe it is for sickle cell patients to use the new therapeutic approach.

Vertex Pharmaceuticals applied for the biologics license with the FDA for the new therapy treatment. The company spearheaded the development of the therapy with CRISPR Therapeutics.

CRISPR’s Chief Executive Officer calls the groundbreaking therapy for sickle cell disease an “exciting milestone.”

The gene modification uses the patient’s own hematopoietic stem cells to produce “high levels of fetal hemoglobin,” which carries oxygen within red blood cells, Vertex explains in a press release.

“The elevation of hemoglobin by exa-cel has the potential to reduce or eliminate painful and debilitating vaso-occlusive crisis (VOC) for patients,” Vertex adds.

“We are glad to see that the unmet need and urgency for innovative therapies in SCD was recognized by the FDA with Priority Review,” Dr. Samarth Kulkarni, Chief Executive Officer of CRISPR Therapeutics, said in a press release.

Earlier this year, NPR reported on a woman, 37, living with sickle cell disease who received the experiential treatment. She says the treatment has made a “huge difference” in her life.

“The life that I once felt like I was only existing in, I am now thriving in,” Victoria Gray said of the gene-editing treatment.

Gray, a mother of four, was part of a cohort of sickle cell patients with severe disease cases who received the treatment. Most patients who participated in the experimental treatment had no symptoms once they completed it. Due to that success, the companies behind the therapy sought FDA approval for the treatment of severe sickle cell and beta-thalassemia, which is a rare blood disorder that causes low hemoglobin, limiting the amount of iron-containing proteins in the blood.

WATCH: Understanding the types of blood disorders.

Before the Oct. 31 advisory meeting, the FDA concluded that exa-cel is “highly effective at preventing episodes of excruciating pain that plagues sickle cell patients. The treatment worked in 29 of 30 patients followed for at least 18 months” without short-term safety concerns. The advisory meeting will further assess any long-term safety concerns.

The FDA will announce its decision regarding exa-cel therapy using gene editing in December.

Better Understanding CRISPR Gene Editing

“CRISPR editing is basically two parts. It’s a molecule that finds that needle in the haystack, the exact place in the genome where we want to rewrite the code around the DNA,” the renowned immunologist Dr. Carl June explains to SurvivorNet. Dr. June is the Director of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania.

“In our case, we wanted to rewrite it so the gene would no longer function, knocking it out,” he says. “We used three different guide molecules to find the location of where the different treated genes would be. And then, we used the Cas9, which acts like molecular scissors. It cuts DNA on both strands at the site the guide tells them to cut it at.”

“Out of 1,000 different cuts, on average, we found only one in 1,000 was at the wrong site,” he continues, “so, it’s really high precision.”

The approach used for CRISPR is similar to that of CAR T-cell therapy, a technique pioneered by June in which immune cells are engineered to fight the cancer.

Sickle Cell Disease and Why It’s So Painful

Sickle cell disease is a group of blood disorders that can cause issues with circulation, leading to intense pain and organ damage.

In the U.S., most people affected by sickle cell disease are diagnosed with the genetic disorder shortly after birth because newborns are usually tested for sickle cell disease.

“The primary problem with this disease is an abnormal hemoglobin,” Dr. Sophie Lanzkron, Director of the Sickle Cell Center for Adults at Johns Hopkins, tells SurvivorNet.

The three most common types of sickle cell disorders include:

• HbSS – This is also called sickle cell anemia and is the most severe form of the disease.
• HbSC – This type of SCD is typically milder.
• HbS beta thalassemia – This type of SCD includes HbS beta zero and HbS beta plus. Those with “zero” tend to have a more severe form of SCD, while those with “plus” usually have more mild disease.

WATCH: Sickle Cell Disease Symptoms

Hemoglobin protein in the red blood cells that carry oxygen throughout the body.

“The hemoglobin molecules and the red cells stick together, and when they stick together, they form this polymer, this stiff thing inside the red cells that causes the red cell to change its shape,” Dr. Lanzkron continues.

Normal red blood cells are round, but in sickle cell patients, the red blood cells are shaped like a “C, or a sickle farm tool (hence, the name).

The change in shape affects the circulation of these critical red blood cells, meaning proper oxygen does not reach tissues. The result of this process can mean excruciating pain and organ damage for patients, among other symptoms.

“The most common symptoms for all of them are painful episodes,” Dr. Lanzkron said.

“These acute, unexpected excruciating episodes of pain that happen when cells get stuck and areas beyond where the cells get stuck do not get oxygenated,” Dr. Lanskron says.

These episodes of pain are known as pain crises. They can occur in various body parts, such as the chest, abdomen, bones, and joints.

WATCH: Treating Sickle Cell Disease

Some treatments for sickle cell disease depend on the severity of your symptoms, according to the National Heart, Lung, and Blood Institute. Options include:

• Pain medication
• Blood transfusions help patients with low red blood cell count.
• Infection-fighting medicines like penicillin
• Medications that prevent the sickling of red blood cells. These medicines may have side effects such as headache, diarrhea, nausea, fatigue, and fever.
• Over-the-counter medicines exist to help manage the side effects.

“A blood and bone marrow transplant is currently the only cure for some patients,” according to the NHLBI.

Dr. Lanskron says the standard therapy for sickle cell disease is hydroxyurea (sold under brand names Hydrea and Droxia). The drug was approved by the Food and Drug Administration in 1998, according to Dr. Lanskron, and it can be used for several types of SCD.

Hydroxyurea works by helping red blood cells stay rounder and flexible, which can help:

• Reduce the number of sickle cells in the blood
• Decrease pain
• Lower the risk of acute chest syndrome (a possible SCD complication where sickle cells stick together and block the flow of oxygen in vessels in the lungs)
• Reduce the need for blood transfusions

Questions to Ask Your Doctor

If you have been diagnosed with sickle cell disease and are wondering about the symptoms associated with your disease, here are some questions you may consider asking your doctor:

• What are the most common complications for my type of SCD?
• How should I be monitoring for these complications?
• What symptoms warrant a visit to the doctor or hospital?
• How often will I have to be monitored?
• Are there any lifestyle changes I can make to reduce the likelihood of complications?
• What options are available to relieve my pain?

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