Gene-editing therapy CS-101 used in SCD patient for first time
Nigerian woman has been free of vaso-occlusive crises for six months
Correctsequence Therapeutics’ experimental gene-editing therapy CS-101 has been used to treat a person with sickle cell disease (SCD) for the first time.
Prior to treatment with CS-101, the patient — a 21-year-old woman from Nigeria — had been experiencing frequent vaso-occlusive crises (VOCs), or painful episodes caused by blood vessel obstruction. Since receiving CS-101 in February, however, the woman has been completely free from VOCs, according to a company press release.
CS-101 is designed to increase fetal hemoglobin levels in blood cells
Sickle cell is caused by gene mutations that lead to the production of an abnormal form of hemoglobin, the protein red blood cells use to carry oxygen through the body. The abnormal hemoglobin tends to clump in red blood cells, deforming them and making them prone to getting stuck inside blood vessels, which can lead to VOCs.
SCD specifically affects the adult version of hemoglobin. An alternative version of the protein called fetal hemoglobin, or HbF, is made in early fetal development, but usually stops being produced shortly after birth. Some people, however, have mutations that cause HbF to be produced throughout adulthood.
CS-101 is designed to increase HbF levels in blood cells, which is expected to help compensate for the mutated adult hemoglobin and prevent VOCs. Stem cells are collected from a patient’s bone marrow, then modified using gene editing to introduce a mutation that causes HbF to be produced throughout adulthood. The modified cells are then returned to the patient via a stem cell transplant.
This overall strategy is broadly similar to that of Casgevy (exagamglogene autotemcel), an approved gene-editing treatment for SCD that also aims to boost HbF production. While Casgevy uses a gene-editing technology called CRISPR/Cas9, CS-101 uses a different type of technology that, according to Correctsequence, is expected to allow for better HbF production without unintended changes to the cells’ genetic code.
SCD patient experienced no side effects related to gene-editing therapy
This patient from Nigeria was treated as part of an investigator-initiated study at the First Affiliated Hospital of Guangxi Medical University in China.
Before treatment, the patient’s hemoglobin levels were at 67.3 g/L, and HbF accounted for less than 5% of all her hemoglobin. Within six months of treatment, her total hemoglobin levels nearly doubled. Her HbF levels also increased to more than 30% within a month. Since the third month following treatment, her HbF levels have remained above 60%.
No VOCs or side effects related to the gene-editing therapy were reported.
CS-101 is also being developed to treat beta-thalassemia, another disorder marked by abnormalities in hemoglobin. Correctsequence said efforts are underway to enroll people with SCD or beta-thalassemia in further trials. The company also said it expects to soon launch pivotal studies, which are designed to provide data that can be used to seek regulatory approvals of the therapy.
About the Author
