Hopes for sickle cell gene therapy treatment

Scientists from the multi-centre RUBY Trial revealed their findings at the European Hematology Association Hybrid Congress in Frankfurt, Germany.

They presented an update on the efficacy and safety of EDIT-301, an experimental gene editing cell therapy that modifies patients’ blood-forming cells to correct the mutation behind sickle cell disease.

Sickle cell disease is an inherited blood disorder that leads to the production of abnormal haemoglobin, the most important component of red blood cells that transport oxygen throughout the body.

Genetic changes in those with the disease alter the shape of round red blood cells into sickles, impeding their passage through narrow blood cells. This can lead to heart failure, liver failure, stroke, cardiomyopathy, and severe pain, with sufferers having a shortened life expectancy.

Four patients, two of whom are participating in the RUBY Trial at Cleveland Clinic Children’s Hospital, had their stem cells collected for gene editing before undergoing chemotherapy to destroy their remaining bone marrow, leaving room for the repaired cells to be infused back into their bodies.

The data showed new white blood cells in all participants after four weeks, with no severe adverse effects.

Patients also achieved a normal level of haemoglobin and were free of sickle cell-related pain attacks for up to 11 months following therapy.

A novel type of CRISPR gene-editing technology, known as CRISPR/CA12, was used to modify blood cell genomes and facilitate healthy blood cell production. This is the first time it has been used to edit human cells in a clinical trial.

Dr Rabi Hanna, principal investigator and Director of Pediatric Bone Marrow Transplantation at the Cleveland Clinic, hopes the results could mark a step away from blood or marrow transplants, which often require a sibling donor and have the potential for severe graft-versus-host disease.

‘New treatments like this are critical for people who have sickle cell disease. These initial results provide hope that this new technology will continue to show progress as we work toward creating a possible functional cure for this devastating and life-threatening disease.’

The RUBY trial aims to enrol 40 adult patients aged 18-50 with severe sickle cell disease, with patients being closely monitored for up to two years post-treatment.

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