The University of Chicago Medicine Comer Children’s Hospital will be among the first in the country to offer gene therapy for sickle cell disease in patients 12 years and older, after federal regulators approved two new treatments on December 8, 2023.
Thousands of patients with sickle cell disease experience complications including anemia, vaso-occlusive crises (VOCs), acute chest syndrome (ACS) and strokes. The complications, particularly VOCs, can be painful and frequently require hospitalization. The two new gene therapy treatments show promise for eliminating VOCs and other issues associated with sickled hemoglobin and offer an alternative to more traditional bone marrow transplants, where patients receive stem cells from another person.
“I'm excited on behalf of our patient population — our patients deserve cutting-edge therapies,” said James LaBelle, MD, PhD, Director of the Pediatric Stem Cell and Cellular Therapy program at UChicago Medicine and Comer Children’s Hospital. “The results of gene therapies are very promising and carry the hope of being definitive and long-lasting, unlike a drug someone might have to take daily for the rest of their life. And since these treatments are based on a patient’s own stem cells, every patient with sickle cell disease has a readily available stem cell donor: themself.”
How do these new sickle cell gene therapies work?
People with sickle cell disease have a gene mutation that causes their blood cells to produce faulty hemoglobin — a protein that carries oxygen throughout the body — and function incorrectly. Gene therapy uses gene editing technology to fix or compensate for this mutation.
Both of the newly approved gene therapies involve removing a patient’s own stem cells and modifying them before infusing them back into the patient.
One FDA-approved therapy adds a new copy of a gene to the patient’s stem cells, so they produce a functional form of adult hemoglobin.
The other therapy, which helps patients produce a healthy form of fetal hemoglobin in place of unhealthy adult hemoglobin, is the first FDA-approved product to use CRISPR-Cas9 gene editing technology. Fetal hemoglobin, a form of hemoglobin that every person produces in utero and right after being born, does not sickle and carries oxygen normally. The CRISPR-based gene therapy changes existing DNA in the patient’s stem cells to inhibit a specific protein. That protein normally prevents the production of fetal hemoglobin and turns on the production of non-functional adult hemoglobin affected by sickle cell mutations, so inhibiting the protein reverses those effects.
“One of the reasons scientists are excited about CRISPR-Cas9 gene therapy products is that they’re highly targeted and don’t contain any foreign DNA,” LaBelle said. “These properties can potentially make these kind of treatments more targeted.”
Comer Children’s was one of the first nine authorized treatment centers immediately activated for the CRISPR-based sickle cell gene therapy upon FDA approval. UChicago Medicine expects to begin treating patients in the first quarter of 2024.
Gene therapy at UChicago Medicine
Physicians and researchers at UChicago Medicine are no strangers to cell and gene therapies. For example, UChicago Medicine was on the leading edge of CAR T-cell therapy research and clinical implementation in 2017 and surrounding years. Comer Children’s Hospital experts even have specific experience administering these therapies to sickle cell patients after the hospital served as a site for a recently published clinical trial of a sickle cell gene therapy.
The results of gene therapies are very promising and carry the hope of being definitive and long-lasting, unlike a drug someone might have to take daily for the rest of their life.
LaBelle and his colleagues also anticipate more gene therapies to receive regulatory approval in the near future, and they hope to host more clinical trials and lead early clinical implementation.
“As an academic medical center, we are poised to provide new gene therapies to our patients as they are approved while also undertaking the scientific research to understand more about long-term effects — both physical and psychosocial,” LaBelle said.
People across the university are continuing to build the clinical infrastructure needed to support complex therapeutic regimens and treat complex patients while maintaining seamless integration between departments and healthcare teams.
“We're working hard to develop a comprehensive clinic that will not only treat patients with sickle cell disease with gene therapy but also follow them long term and provide ongoing care, including addressing any complications,” LaBelle said. “It’s important that patients are able to access gene therapy without giving up their trusted hematologists and primary physicians.”