Recently, scientists aiming to devise a one-time treatment to relieve symptoms and possibly cure genetic diseases have successfully found a solution.

A new study reported the development of Casgevy, a gene-editing tool made using CRISPR-Cas9 to treat two severe blood conditions – sickle-cell disease and ?-thalassaemia. The process involves editing genes that encode hemoglobin in blood-producing stem cells.

UK medicines regulator – Medicines and Healthcare Products Regulatory Agency (MHRA) is the first to approve this therapy, following the success of clinical trials.

Prospects to employ future CRISPR therapies

Kay Davies, a geneticist at the University of Oxford, stated: “This is a landmark approval which opens the door for further applications of CRISPR therapies in the future for the potential cure of many genetic diseases.”

According to Nature, the treatment is administered by intravenous infusion. Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland, developed the therapy.

Scientists alluding to the success of Casgevy exemplified that the therapy relieved patients of debilitating pain in sickle-cell disease and reduced or eliminated the need for regular blood transfusions in ?-thalassaemia.

“The trial for sickle-cell disease has followed 29 out of 45 participants long enough to draw interim results. Casgevy completely relieved 28 of those people of debilitating episodes of pain for at least one year after treatment,” reported Nature.

In the trials for severe ?-thalassemia, for which the standard treatment entails monthly blood transfusions. Nature reported that out of 54 individuals receiving Casgevy, 42 participated long enough to yield interim results. Among these, 39 didn't require a blood transfusion for a year, while the remaining three saw a reduction of over 70 percent in transfusion needs.

Revolutionary use of CRISPR-Cas9 tool

The revolutionary aspect of this therapy is its utilization of CRISPR-Cas9, a tool that won the Nobel Prize in Chemistry in 2020, to precisely edit genes in blood-producing stem cells.

By targeting a particular gene – BCL11A, Casgevy triggers the production of fetal hemoglobin, which can alleviate symptoms by improving oxygen supply to tissues.

However, clinical trials observed certain side effects in participants, including nausea and fever, but major safety concerns were undetected.

However, scientists noted concerns about potential unintended genetic modifications by CRISPR-Cas9, which are being monitored.

David Rueda, a geneticist at Imperial College London, told the SMC stated:

“It is well known that CRISPR 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 concluding. Nonetheless, this announcement makes me feel cautiously optimistic.”

Other countries, including the US and Europe, are reviewing Casgevy for approval. However, the high cost and complex technology involved might limit its accessibility, especially in low- and middle-income countries.

Calculations indicate that the therapy might cost around US$2 million per patient, posing a substantial accessibility limitation.

“The challenge is that these therapies will be very expensive, so a way of making these more accessible globally is key,” Davies noted.

A Vertex representative told Nature: “We have not established a list price for the UK at this time and are focused on working with the health authorities to secure reimbursement and access for eligible patients as quickly as possible.”