Deoxyribonucleic acid – or DNA – testing is a very exciting frontier for sickle cell disease, specifically for African-Americans, said Dr. Lanetta Bronté, president of the Foundation for Sickle Cell Disease Research, a comprehensive nonprofit that provides a platform for researchers, healthcare providers, and those living with the monogenic disorder.
“Many that are DNA-tested learn their true genetic heritage for the first time. Next, if they are unaware of their sickle cell trait status, they need to visit participating medical centers to know with certainty if they have sickle cell trait or not,” Bronté said.
Approximately 2 million people have the sickle cell trait and a majority don’t know.
That and the DNA revolution counts among the highlights of the Foundation for Sickle Cell Disease Research’s 12th annual Sickle Cell Disease Research & Education Symposium at the Marriott Wardman Park in Northwest from June 15 to 17.
Dr. Philippe Leboulch is scheduled to be the scientific keynote speaker at the symposium and is expected to provide an update on his progress with the development of LentiGlobin BB305 for therapeutic ex vivo gene transfer in severe sickle cell disease.
Leboulch’s vector made headlines last year with a 13-year-old sickle cell patient in Paris. Fifteen months after receiving the innovative treatment, the patient is now in complete remission of clinical signs of sickle cell disease and correction of any biological signs, Bronté said.
“The patient no longer needs to be transfused or suffers from vaso-occlusive crises. The patient will also avoid developing the potential co-morbidities many sickle cell disease patients have,” she said.
While gene therapy remains very risky, this early work shows how beneficial it can be for a sickle cell patient, Bronté added.
“This is an exciting time to be involved with sickle cell disease, as there are new treatments, expanding research, and a community of advocates determined to improve the quality of these patients’ lives,” she said.
Despite being the first “molecular disease” ever discovered and the most common genetic disease in the US, sickle cell disease has no universal cure and is a devastating disease that predominantly affects people from African descent, who are long under- and unequally-served by the medical and research communities, said Michael Friend, who co-founded the Minority Coalition for Precision Medicine with sickle cell patient advocate, Shakir Cannon.
Friend, who presented a seminar last month on sickle cell, said the disease is getting renewed attention as CRISPR researchers set their sights on finally curing it at the DNA level using gnome editing.
Scientists have successfully used gene editing to repair 20 to 40 percent of stem and progenitor cells taken from the peripheral blood of patients with sickle cell disease, Rice University bioengineer Gang Bao told Science Daily last month.
Bao, in collaboration with Baylor College of Medicine, Texas Children’s Hospital and Stanford University, is working to find a cure for the hereditary disease.
A single DNA mutation causes the body to make sticky, crescent-shaped red blood cells that contain abnormal hemoglobin and can block blood flow in limbs and organs.
In his talk at the annual American Association for the Advancement of Science meeting in Austin, Bao revealed results from a series of tests to see whether CRISPR/Cas9-based editing can fix the mutation.
His presentation was part of a scientific session titled “Gene Editing and Human Identity: Promising Advances and Ethical Challenges.”
“Sickle cell disease is caused by a single mutation in the beta-globin gene – in the stem cell’s DNA,” he said, according to Science Daily.
“The idea is to correct that particular mutation, and then stem cells that have the correction would differentiate into normal blood cells, including red blood cells. Those will then be healthy blood cells,” he said.
Dr. Charles S. Abrams, an expert with the American Society of Hematology and the Francis C. Wood Professor of Medicine in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania’s Perelman School of Medicine, said sickle cell disease has been described in various tribes in African for more than 5,000 years.
“It was discovered approximately 100 years ago by Dr. Ernest Irons when he noticed a dental student named Walter Clement Noel had red blood cells with the shape of a sickle,” Abrams said.
“Red blood cells are basically bags of hemoglobin. Everyone with sickle cell disease has a change – or mutation – in the DNA of their hemoglobin gene,” he said.
Abrams continued: “This mutation causes their hemoglobin to be abnormal, and consequently the red blood cells sometimes have this sickle shape. A variety of lab tests, including genetic tests can be done to diagnose an individual and to determine the risk of passing the sickle cell gene onto their children.”
In Bao’s lab, he collaborated with Vivien Sheehan, an assistant professor of pediatrics and hematology at Baylor and a member of the sickle cell program at Texas Children’s, to collect stem and progenitor cells (CD34-positive cells) from patients with the disease, Daily Science said.
These were then edited in the Bao lab with CRISPR/Cas9 together with a custom template, a piece of DNA designed to correct the mutation.
The gene-edited cells were injected into the bone marrow of immunodeficient mice and tested after 19 weeks to see how many retained the edit.
“The rate of repair remained stable, which is great,” Bao said. This engraftment study was carried out in the lab of Matt Porteus, an associate professor of pediatrics at Stanford.
Another major finding of the study is that the CRISPR/Cas9 system could introduce large alterations to the genes in patients’ cells, in addition to small mutations or deletions.
These off-target effects could cause a disease.
The findings, part of an upcoming paper, are a step toward treating sickle cell disease. Obstacles in the way of a cure include optimizing the CRISPR/Cas9 system to eliminate off-target effects, as well as finding a way to further increase the amount of gene-corrected stem cells, according to Science Daily.
Bao pointed out that researchers still don’t know whether repairing as much as 40 percent of the cells is enough to cure a patient.
“We’d like to say, ‘Yes,'” he said. “But we don’t really know yet. That’s something we hope to learn from an eventual clinical trial.”