Sickle cell disease refers to a group of genetic diseases that impact a protein that ferries oxygen through the blood. That protein is called hemoglobin, and in sickle cell disease, aberrant hemoglobin creates misshapen red blood cells. These cells will not easily bend or move and may obstruct blood flow, which can cause major complications. Sickle cell patients may also experience chronic pain, eye problems, and kidney disease, among other health issues.
Scientists have now treated a sickle cell patient successfully with a gene therapy known as base editing. In this trial, which was called BEACON, cells of sickle cell patient Branden Baptiste were collected and exposed to a virus that delivered the genetic instructions for creating normal hemoglobin into those cells. The treated cells were then returned to the patient.
Non-pathogenic viruses are typically used to send gene editing reagents into cells because they can infect cells, but are not meant to cause harm.
Gene therapy treatments may sometimes involve making cuts to the genome, which could lead to a host of unintended effects. But another strategy aims to merely swap out one base letter of DNA for another, in a technique known as base editing.
Branden was the world's first person to receive base editing for sickle cell disease, and is one of the first to get it for any reason. He first had sickle cell symptoms at age 2, and his symptoms were only getting worse as he got older.
In this method, the researchers removed blood stem cells from Branden, which were then exposed to the virus that delivered the gene editing reagents. The scientists also had to remove the existing blood stem cells from Branden, so there was a home for the treated cells. He was in the hospital for several weeks under observation.
He felt so good and recovered so well after the treatement, he was released from the hospital early, and is continuing to do well after about a year. He has been able to stop taking all of his sickle cell medication and is feeling good. He is also now able to exercise, which he could not do before this treatment.
"In my opinion, I'm perfect. I never felt fine before; before, 'fine' was moderate pain. I could take deep breaths through. Now I'm more than fine. I'm operating in every way possible," Branden said. The team plans to continue to monitor his condition for several more years.
"Sickle cell disease has a broad spectrum of severity, and the severity and frequency of complications can wax and wane," said Matthew Heeney, MD, a hematologist at Boston Children's Hospital who has treated Branden for many years.
"The treatment has been truly transformative for Branden," Heeney added. "Not only are his blood counts and markers of disease activity essentially normalized, but he can now complete daily activities that most take for granted and tackle new experiences previously beyond his reach. It is a joy to see him setting goals that seemed unfathomable just a year or two ago."
Sources: NHLBI, Children's Hospital of Boston