New Gene-Editing Approach Eliminates Painful Crises in Sickle Cell Disease New Results From A Clinical...

New results from a clinical trial show promising outcomes for a gene-edited treatment for severe sickle cell disease, a genetic blood disorder with few curative options.

Conducted as part of the multicenter RUBY Trial, researchers published their latest findings in the New England Journal of Medicine. Remarkably, 27 out of 28 patients did not have any painful sickle cell crises after treatment, achieving what physicians call a "functional cure."

In the trial, patients were treated with an experimental one-time gene editing cell therapy – Renizgamglogene autogedtemcel (reni-cel) – that modifies a patient's own blood-forming stem cells to correct the mutation responsible for sickle cell disease. The novel therapy increases levels of fetal hemoglobin – which prevents red blood cells from forming into sickle-shaped cells – and improves overall hemoglobin levels, reducing complications from the disease.

"We have seen that a benefit of this CRISPR/Cas12a gene-editing technology is that there is no rejection, so it's different from traditional bone marrow transplants, which is standard treatment for sickle cell patients currently," says Rabi Hanna, M.D., lead author and chair of the Pediatric Hematology – Oncology & Blood and Bone Marrow Transplant Division at Cleveland Clinic Children's.

"Our aim has been to achieve a functional cure to help prevent any future damage caused by sickle cell disease, and these latest results are compelling."

Rabi Hanna, M.D., Cleveland Clinic Children

The 28 patients – four of whom were treated at Cleveland Clinic Children's – underwent a procedure where their stem cells were first collected for gene editing. They then received chemotherapy to clear their bone marrow, making room for the repaired cells which were later infused back into their body.

The results showed that most patients saw key blood cells recover within a month after treatment and by six months, average total hemoglobin levels rose to 13.8 g/dL, up from 9.8 g/dL before treatment – a level closer to what is seen in people without sickle cell disease. The average level of fetal hemoglobin (HbF) was 48.1 %, and these levels remained stable over time.

Sickle cell disease is a genetic blood disorder that causes red blood cells to be misshapen like a sickle. Normal red blood cells are round and carry oxygen smoothly through blood vessels. In sickle cell disease, the abnormal cells block blood flow and break apart easily, leading to complications such as severe pain, liver and heart issues, and a shorter life span, typically in the mid-40s. Medications can help manage the disease, but a cure is possible only through a blood or marrow transplant, which has risks and often requires a sibling donor.

Cleveland Clinic has a specialized center for the care of adults and children with sickle cell. It provides comprehensive care, including treatment and support services throughout a patient's lifetime, beginning in childhood.