10/05/2025
Gene Therapy for Sickle Cell Disease
Offers Patient New Lease on Life
Marie-Chantal Tornyenu, now 23, was diagnosed with sickle cell disease at birth. Her
father, Daniels Tornyenu, also has the disease.
(photo courtesy of Marie-Chantal Tornyenu)
By Lauren Ingeno
Since she was a child, Marie-Chantal Tornyenu, now 23, was plagued by a "hollow
burning" in her chest, which landed her in the hospital nearly every month by the time
she entered high school.
"And then you can't breathe on top of it," she said. "It felt like ice almost. I would wake
up, and I couldn't move."
Tornyenu is among the 100,000 Americans — most of them African American — who
are affected by sickle cell disease, a lifelong genetic disorder. Patients have a single gene
mutation that prevents the body from making normal hemoglobin, the protein in red
blood cells responsible for delivering oxygen throughout the body. The mutation causes
hemoglobin molecules to stick together, hardening red blood cells into C-shaped
"sickles," which can clog blood vessels and lead to intense pain episodes.
While a bone marrow transplant is one potential cure, Tornyenu didn't have a matching
donor. But her life changed in 2021, when she enrolled in a clinical trial at Children's
Hospital of Philadelphia.
The trial tested a new gene therapy called exa-cel (Casgevy®, Vertex and CRISPR
Therapeutics) — the first-ever treatment to use the Nobel Prize-winning
CRISPR technology to edit a patient's DNA as a potential cure for disease.
Stephan Grupp, MD, PhD
"Gene therapy allows us to treat patients in a completely different way," said Stephan
Grupp, MD, PhD, Section Chief of Cellular Therapy and Transplant, who led the exa-cel
trial at CHOP. "We take their own cells, fix the problem, and give their cells back,
without the significant risks of donor transplant."
Simultaneously, CHOP also served as a clinical trial site for lovo-cel (Lyfgenia®,
bluebird bio), a gene therapy that treats sickle cell by delivering a modified hemoglobin
gene into the body via a viral vector. That trial was led by Janet Kwiatkowski, MD,
MSCE, Director of CHOP's Thalassemia Center and Clinical Director of
the Comprehensive Center for the Cure of Sickle Cell Disease and Other Red Blood Cell
Disorders (CuRED) Frontier Program.
Janet Kwiatkowski, MD, MSCE
During clinical trials for both gene therapies, more than 90% of patients had no
debilitating pain episodes for at least one year, and the treatments had positive safety
profiles.
In early December 2023, the U.S. Food and Drug Administration approved both gene
therapies — exa-cel and lovo-cel — for patients 12 years and older with recurrent vaso
occlusive crises.
The approval of the revolutionary treatments marked a turning point for an underserved
patient population and could revolutionize the future of treatment for numerous other
medical conditions. As CHOP and other centers bring these new approaches to the
bedside, the hope is their experiences will inform how to offer the treatments to more
U.S. communities, and potentially, throughout the world.
Alexis Thompson, MD, MPH
For patients like Tornyenu, having access to a curative treatment could be life-changing,
said Alexis Thompson, MD, MPH, Chief of the Division of Hematology at CHOP. Living
with sickle cell disease often means dealing with the unpredictability of symptoms while
taking frequent trips to the emergency room and managing other chronic complications.
"When we think about an option that is curative, it really has two important
considerations," Dr. Thompson said. "One is the possibility that the individual will be
freed of the burden of this disease. The other is the hope that these individuals no longer
require the degree of care and the expenses related to that care, and instead can look
forward to having more full lifespans where they finish their educations, have jobs, raise
families, and live the lives that they want."
“NOW, I CAN SEE MYSELF LIVING INTO MY 80S OR 90S," SAID TORNYENU, WHO
GRADUATED FROM CORNELL UNIVERSITY IN THE SPRING AND HAS PLANS
FOR LAW SCHOOL. "I CAN IMAGINE THE LIFE I'LL HAVE FOR MYSELF. ”
While the approvals of both exa-cel and lovo-cel offer new possibilities to a patient
population that previously had few treatment options, gene therapy is not a quick and
easy fix. The process can take up to a year from start to finish and comes with many
complexities.
Marie-Chantal Tornyenu graduated from Cornell University in the spring.
Helping CHOP patients navigate the arduous gene therapy process are specialists in the
CuRED Frontier Program who support the patient and family through a streamlined
care model. The Center offers a multidisciplinary clinic for evaluation and treatment of
children with sickle cell disease, beta thalassemia, and other red cell disorders.
For decades, CHOP researchers have been at the forefront of developing therapies for
sickle cell and other genetic disorders. More work toward cell and gene therapy
solutions is ongoing at laboratories at CHOP, as researchers continue to search for red
blood cell disease treatments that are safer, easier to administer, and cost-effective for a
large and diverse patient population.
Tornyenu’s life changed in 2021, when she enrolled in a clinical trial at CHOP. The
treatment has given her a new outlook on a future she didn't think was possible just a
few years ago.
