Hemophilia gene therapy: encouraging progress
As part of a phase 1 clinical trial by a scientist from University College London and St. John's Children's Research Hospital.Judas (Memphis, USA) managed to significantly improve the condition of six adult patients with hemophilia B with the help of a single application of gene therapy.
All participants were treated at the free Royal London Clinic under the supervision of Professor Edward Tuddenham. After the procedure, four patients stopped injecting themselves with a blood clotting factor, which did not lead to spontaneous bleeding. At the same time, some of them took part in marathons and other events, which previously would have been completely impossible.
Hemophilia B is a hereditary disease caused by a mutation of the gene encoding clotting factor IX, a protein necessary for the normal formation of blood clots. This gene is localized on the sexual X chromosome, so the disease occurs almost only in men. The frequency of this mutation is approximately 1 in 30,000 people.
Earlier attempts to alleviate the symptoms of hemophilia B by injecting the "correct" version of the gene into the patient's cells were unsuccessful.
As part of the latest work, the researchers used adenoassociated virus 8 (AAV-8) to deliver the coagulation factor IX gene and additional genetic material to the patient's liver. This virus was chosen because of the low frequency of natural prevalence in the human population. It belongs to the family of viruses that infect liver cells, but do not cause diseases in humans and do not integrate into human DNA. Before the therapy, the study participants did not receive immunosuppressive drugs.
The procedure consisted of a single injection into the ulnar vein of each of the patients containing a viral vector. The patients were previously divided into 3 groups (2 people each), who received different doses of the gene therapy drug. After the procedure, the levels of clotting factor IX in all patients increased from less than 1% to 2-12% of the normal index.
The most pronounced increase in the concentration of clotting factor IX was observed in patients of the group that received the highest dosage of the vector. However, according to the head of the study, Dr. Andrew Davidoff, in order to significantly improve the quality of life of patients and reduce the frequency of bleeding, even a moderate, but exceeding 1% of the normal concentration, level of this protein is sufficient.
The first participant of the study was under observation for the longest time. At the same time, the concentration of clotting factor IX in his blood remained at the level of 2% of the normal value for more than 18 months. These results are more than impressive, and researchers are already attracting new patients to participate in a future clinical trial, which is scheduled to begin in the near future.
One of the patients who received the largest dose of the drug underwent a short course of steroid therapy due to increased levels of liver enzymes. This symptom indicates minor damage to the liver, which did not affect the patient's overall health. The second patient of this group also received a short-term course of steroid therapy due to an increase in the concentration of liver enzymes, which, however, remained within the normal range.
The researchers believe that the increase in liver enzyme levels was caused by an immune response triggered by a viral vector. A similar reaction from the liver was observed earlier in a clinical trial using a different vector developed by another group of researchers.
Article by Amit C. Nathwani et al. Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B is published in the New England Journal of Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of University College London:
Gene therapy achieves early success against hereditary bleeding disorder.
12.12.2011