Sickle cell disease: Gene therapy advances, but access and interest gaps persist

Financial challenges continue to limit access to treatment for patients with sickle cell disease even as high-tech treatments are advancing rapidly, a researcher at St. Jude Children’s Research Hospital told science writers gathered for a conference in Memphis, Tenn. on Oct. 23.

Mitchell Weiss, Arthur Nienhuis Endowed Chair in Hematology at St. Jude, said sickle cell anemia, one of the first diseases tackled by the hospital after its founding in 1962, serves as a case study in several important health topics, including racial health inequities, successes with experimental treatments such as gene therapy, and the challenges of bringing those treatments to a wide group of patients.

Sickle cell disease is estimated to occur in one in 365 Black births in the U.S.  It affects three times as many people as cystic fibrosis, a disease concentrated in white patients, but cystic fibrosis gets three times as much research funding.

“The sickle cell disease community has developed a significant lack of trust in the health care system due to the nearly universal stigma, the lack of belief in reports of pain, and a lack of trust that has been further reinforced by historical events such as the Tuskegee Experiment,” said Mitchell Weiss, Arthur Nienhuis Endowed Chair in Hematology at St. Jude. He spoke during the New Horizons in Science Briefings presented by the Council for the Advancement of Science Writing as part of the ScienceWriters2022 conference.

Sickle cell disease is an inherited group of disorders that cause red blood cells to become misshapen and break down and die early, leaving a shortage of healthy red blood cells that can block blood flow, causing pain infections and fatigue. Although caused by a single genetic mutation, it can be different in every patient. Many diagnostic challenges remain, Weiss said, adding that current treatment options are limited and often complicated by the disease itself. Recently, advances in gene therapy and gene editing technology have shown promise in experimental treatments for the disease.

“We now have targeted pathways, and technologies from manipulating genomes have advanced at blinding speed,” Weiss said. “We have all these ways now that we can manipulate the genome to impact these biological processes that have just been discovered.”

Red blood cells use the protein hemoglobin to capture oxygen and ferry it throughout the body. The hemoglobin in adult red blood cells is made up of different sub-units than the protein produced during fetal development. When the gene for fetal hemoglobin is expressed after birth, it alleviates the symptoms of sickle cell disease.

St. Jude researchers recently published a paper in the journal Nature showing how a protein responsible for adapting to low-oxygen conditions (hypoxia) promotes increased expression of the gene for fetal hemoglobin in adults. This link suggests a possible treatment for sickle cell and other serious blood disorders that affect millions of individuals.

Patient advocate April Ward-McGrory told the audience of science writers about her lifetime experience of living with sickle cell disease, which she says most people—including those who have family members with the disease—understand poorly and know little about.

“If any of you ever come in contact with someone with sickle cell disease, remember that bubbly lady in the wheelchair and that empathy goes a long way,” said Ward-McGrory. “And just remember, it doesn’t matter what we look like, our pain is real.”