Update 10/12/2020: CRISPR Therapeutics and Vertex have since released the results of a total of 7 patients with ?-thalassemia and 3 patients with sickle-cell disease. Dosed with the same CTX001 treatment as the patients below, results were consistent across the entire set of participants, with all 10 patients either no longer requiring transfusions or being completely free of vaso-occlusive crises after the follow-up period.
Two patients that received CRISPR-Cas9 gene-editing a year ago no longer need blood transfusions, states a study published in the New England Journal of Medicine. The results are promising for patients with two potentially life-threatening single-gene disorders.
The trials followed two patients, one with sickle-cell disease (SCD) and the other with transfusion-dependent ?-thalassemia (TDT), involved in CRISPR-based gene therapy called CTX001. Patients with these conditions do not produce enough fetal hemoglobin, a molecule that carries oxygen through the blood to all the cells in our body.
Produced by Vertex Pharmaceuticals and CRISPR Therapeutics, CTX001 edits the DNA of patients to boost the production of fetal hemoglobin in their red blood cells in an attempt to combat the diseases.
Patient 1 has ?-thalassemia, an inherited blood disorder in which the body does not produce enough of an important chain that makes hemoglobin, creating a defective version that is far less effective than the healthy counterpart. Due to this defective hemoglobin, the patient cannot transport oxygen efficiently and may feel tired, weak, and short of breath. Transfusion dependent ?-thalassemia is the most severe type of this condition and, if left untreated, can lead to severe anemia and subsequent death. As a result, patients require regular blood transfusions to offset the lack of functional hemoglobin in the blood.
Prior to the study, the patient had received an average of 34 units (roughly equivalent to 18 liters) of red blood cells per year. However, after treatment with CTX001, the patient’s fetal hemoglobin levels rapidly rose within 6 months and this level was maintained for 18 months. The patient no longer requires blood transfusions.
The results are equally as promising for patient 2 who suffers from sickle-cell disease, an inherited blood condition in which the body produces abnormally shaped blood cells that usually die quicker than healthy blood cells but can also stick together and block blood vessels. Patients with SCD have regular episodes of intense pain, called a vaso-occlusive crisis, in which the blood vessels become blocked. Vaso-occlusive crises are the most common reason for patients with SCD to seek medical attention, and severe episodes can be fatal.
Before treatment with CTX-001, patient 2 averaged seven crises per year. After treatment, the patient had no crises in the 16.6 months during the study’s duration and saw a rise in fetal hemoglobin similar to patient 1.
The results suggest the CTX001 therapy is promising for these two disorders and is now being rolled out further on a larger cohort of eight patients to gain more data. Whilst the results showed immediate improvements, it is important to note that some undesirable side-effects were noted.
Both patients had a variety of low-grade side-effects, and patient 1 had two serious events including one infection with pneumonia. The scientists attribute this to a delay in immune system recovery following treatment, which is also seen in another form of immune cell transplantation treatment. Patient 2 suffered from severe sepsis, again likely due to a delayed immune recovery, but all side-effects were resolved with treatment.
CRISPR-based therapies have gained significant momentum in the last few years, and with such rapid results following treatment, it is easy to see why. However, these treatments still require significant testing to prove they are reliable and safe in the long term. It also remain to be seen whether or not the results will translate to a variety of patients. There have been previous studies that identified safety concerns, including an elevated risk of cancer and possible off-target gene-editing, which need to be strictly studied before mass deployment of the treatment. Furthermore, with great innovation comes great cost, and CRISPR is no exception. With pharmaceutical companies charging up to $2 million for a similar treatment to the one presented in this study, widespread availability may be a long way off.