The UK is the earliest country to approve use of the world’s first gene therapy for treating sickle cell disease.
Over 8 million patients around the globe live with sickle cell disease (also known as sickle cell anaemia), an inherited blood disorder that causes the body’s red blood cells – responsible for carrying haemoglobin, a protein that binds to oxygen and delivers it to tissues and organs throughout the body – to become misshapen (forming a ‘C’ or ‘sickle’ shape) and not last as long as healthy cells, potentially leading to anaemia.
Researchers estimate about 250 million people globally carry the gene that causes it; to date, most treatment involves medications and surgical procedures including blood transfusions and bone marrow (stem cell) transplants, which can be invasive and come with potential complications.
Because it is genetic, a person can only get it if they receive the gene from both biological parents; symptoms start to appear within the first year of life, typically around age 5 months.
Patients living with sickle cell disease experience significant pain due to red blood cell ‘clumps’ forming in the bloodstream, and are also at a higher risk for infections, stroke, vision loss, blood clots, sleep disorders, kidney problems and liver issues.
In 2021 a study in the New England Journal of Medicine reported successful ‘gene editing’ to allow the foetal haemoglobin gene to be switched off at birth, triggering the other non-faulty foetal haemoglobin gene to be transcribed instead.
The new gene therapy approved by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) is called Casgevy (exagamglogene autotemcel) and is based on the 2021 gene editing tool. It is authorised for use in people aged 12 or older with sickle cell disease and certain specifications.
Casgevy ‘met its primary outcomes of leaving study participants with sickle cell disease or transfusion dependent beta-thalassemia free from having severe vaso-occlusive crises or being transfusion-dependent for at least 12 consecutive months, in a clinical trial for each condition’, noted medicalnewstoday.com.
Professor David Rueda at Imperial College London told Science Media Centre the MHRA approval of Casgevy ‘is excellent news for the patients and the gene therapy scientific community. The published results of the clinical trial look very promising, too.’
But he cautioned the therapy ‘can result in spurious genetic modifications with unknown consequences to the treated cells. It would be essential to see the whole- genome sequencing data for these cells before coming to a conclusion.
‘Nonetheless, this announcement makes me feel cautiously optimistic.’
And Professor Dame Kay Davies at the University of Oxford added: ‘This is a landmark approval which opens the door for further applications in the future for the potential cure of many genetic diseases.’
