Millions of people could now be cured of sickle cell disease, a serious inherited blood condition, thanks to CRISPR gene editing 鈥� but the cost of treatment is so high that few people are likely to receive it in the foreseeable future.
Humanity is 鈥渁ble to cure sickle cell disease using gene editing,鈥� at the Muhimbili University of Health in Tanzania told the International Summit on Human Genome Editing in London on 6 March. 鈥淭his is, in my opinion, one of the greatest achievements in modern history.鈥�
Several other speakers emphasised the need to make the treatment accessible to those who need it. of the National Alliance of Sickle Cell Organization in India pointed out that many people with the condition still don鈥檛 have access to a relatively cheap drug called hydroxyurea that has been used to treat sickle cell symptoms for 40 years, let alone more advanced treatments. 鈥淲e are still waiting,鈥� he said.
Advertisement
Funding gene-editing treatments will be an issue even in high-income countries such as the US, says at the Institute for Clinical and Economic Review in Boston.
Many of the 100,000 or so people with sickle cell disease in the US are on state-funded Medicaid, he told 快猫短视频, and states don鈥檛 have nearly enough money to pay for all of them to have the CRISPR treatment.
Sickle cell disease is caused by mutations in both copies of the gene for haemoglobin, the red protein in blood that carries oxygen. This results in sickle-shaped red blood cells that can block capillaries, damaging organs and causing episodes of severe pain.
鈥淭he pain was like being struck by lightning and hit by a freight train all at the same time,鈥� says Victoria Gray, who was frequently hospitalised during severe episodes and required in-home care. 鈥淢y life was just dreadful.鈥�
Around 5 to 7 million people worldwide have sickle cell disease, of the Gates Foundation told the summit. In Africa, only around 10 per cent of those born with the condition reach adulthood, but in other regions screening programmes have greatly reduced childhood mortality.
There are now several drugs for tackling the symptoms and people can also be treated by replacing the blood stem cells in their bone marrow with those from a donor who doesn鈥檛 have the condition. However, this requires taking immunosuppressing drugs, for life, to prevent rejection and so isn鈥檛 a complete cure, which is why researchers turned to CRISPR.
Key to this effort is the fact that there are both fetal and adult haemoglobin genes. The former are normally switched off around birth, but in some people it remains switched on. These people continue to produce fetal haemoglobin as adults and, even if they have two mutated copies of the adult gene, don鈥檛 develop sickle cell disease.
Several groups have been developing treatments based on reactivating fetal haemoglobin production in people鈥檚 own blood stem cells, instead of using cells from a donor. In 2018, Gray was the first to be offered an experimental treatment developed by Vertex Pharmaceuticals.
鈥淚 had nothing to lose,鈥� she says. 鈥淚 wanted to be able to dress my daughters for their weddings and be there while they signed up for college.鈥�
In 2019, blood stem cells were taken from Gray and gene-edited to reactivate the fetal haemoglobin. After treatment to destroy her remaining blood stem cells, the gene-edited cells were transferred back to Gray鈥檚 body and have cured her of the disease.
After successful results in 31 people with sickle cell 鈥� none experienced severe episodes after treatment 鈥� and in 44 people with the related blood condition beta thalassaemia, Vertex Pharmaceuticals last year applied for approval in the US and the European Union. It is virtually certain to be approved by the US regulator in around three months or so, says Pearson.
The pricing hasn鈥檛 been announced, but similar treatments approved recently have cost between $1 million and $3.5 million, the summit heard. Part of the issue is the personalised nature of the treatment, as people must receive edited copies of their own cells.
This is why the Gates Foundation is funding research into how to alter blood stem cells inside the body, Turner told the summit, rather than having to remove and replace them. This approach could lead to 鈥渙ff-the-shelf鈥� treatments that could be given to everybody, greatly reducing costs.
at the Children鈥檚 Hospital of Philadelphia told 快猫短视频 that while sickle cell disease is now technically curable, she won鈥檛 regard the condition as actually curable until those who need it are able to get treatment. She also struck a note of caution, pointing out that we don鈥檛 yet know how those who received the gene-editing therapy will fare in the longer term.
But for Gray, the immediate difference is clear. 鈥淭he feeling is amazing,鈥� she says. 鈥淣ow everything is different for me, and life is full of options.鈥�
Article amended on 9 March 2023
We have corrected the name of Vertex Pharmaceuticals
