Chinese researchers have made what they claim is "a historic breakthrough" in the treatment of haemophilia, an inherited disorder that can cause unstoppable bleeding.
They designed gene therapy drug BBM-H901 to treat haemophilia B and have found it to be safe and effective in preventing bleeding events a year after infusion.
After 58 weeks of treatment, the average level of clotting factor activity of 10 patients included in the study increased from less than 2 per cent to 36.9 per cent, according to the study published last week in The Lancet Haematology.
In haemophilia, the level of clotting factor activity is closely linked to the severity of the disease. Normal clotting factor activity ranges from 50 to 120 per cent and a severe haemophilia B patient may have an activity of zero or less than 1 per cent. Individuals with factor levels between 20 and 40 per cent rarely have spontaneous bleeding, according to the researchers
"In our long-term follow-up, only one patient had received replacement therapy due to aggravation of a previous haematoma. No other patients had excess bleeding, which greatly reduced their pain," the researchers said in a statement.
"The increase of patients' clotting factor activity levels and the stopping of bleeding represented a 'clinical cure' for patients to live like normal people without constantly worrying about bleeding," they said.
"The study has achieved the best treatment results internationally ... and it takes curing incurable haemophilia B from a hope to a reality."
The researchers are from the Institute of Haematology and Blood Diseases Hospital at the Chinese Academy of Medical Sciences, the East China University of Science and Technology and Belief BioMed, a Shanghai-based innovative gene therapy company.
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Zhang Lei, the corresponding author of the study and deputy head of the hospital, said the study was significant for China.
"China has about 120,000 haemophilia patients and about 40,000 registered patients, of which 75-80 per cent are haemophilia A patients and 15-20 per cent are haemophilia B patients," he said.
"Most of them are severe patients who need continuous replenishment of clotting factors, resulting in heavy financial burdens. Some of the patients have joint damage, or even disability," he said.
"There are a series of international clinical trials and we Chinese medical scientists also want to cure this disease through gene therapy."
Haemophilia is mainly caused by mutations in clotting factor genes. Haemophilia A is caused by a lack of blood clotting factor VIII and haemophilia B is caused by a deficiency in factor IX.
Patients must inject clotting factors throughout their lives to help control bleeding. Therefore gene therapy, which aims to cure the disease by injecting the correct genes into patients to replace the abnormal or mutated genes and express the correct protein or molecule, has become a cutting-edge technology.
Scientists tended to use adeno-associated viral (AAV) vectors as a delivery mechanism for gene therapy, but it might cause an immune response, Zhang said.
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Zhang and his colleagues used glucocorticoids to suppress the immune response to AAV to reduce the adverse effects. They also used single-cell RNA sequencing to monitor AAV-specific immunity, a method carried out for the first time in such studies.
"To our knowledge, this is the first trial of AAV-based liver directed gene therapy in patients with haemophilia B done in China," the researchers said.
Zhang said his team would apply to carry out the second and third phases of the clinical trial which could include between 30 and 50 people.
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