造血干细胞基因疗法,X链慢性肉芽肿病 z-bo 2020-09-30 330

　　X-chain chronic granulomatous disease (X-chain chronic granulomatous disease, X-CGD) is a rare inherited blood disease. It can cause repeated infections, prolong hospital stays and shorten lifespan. Prior to this, X-CGD patients must resort to bone marrow donation to get a chance of remission.

　　In a new study, researchers in the United Kingdom, the United States, France, and Germany reported the use of stem cell gene therapy to treat 9 X-CGD patients. Six of them are currently in remission and are stopping other treatments.

　　The co-author of the paper, Dr. Donald Kohn of the Eli and Edith Broad Center for Regenerative Medicine and Stem Cell Research at the University of California, San Francisco, said: “This gene therapy allows the use of the patient’s own stem cells. The donor cells are transplanted. This means These cells are very suitable for patients. Immune rejection. This should be a risk-free and safer transplantation method."

　　In patients with chronic granulomatous disease (CGD), white blood cells use a variety of chemicals to attack and destroy bacteria and fungi. One of the five genes that contribute to inheritance is genetic mutation. Without this protective chemical, patients with this disease are more susceptible to infection than most people. These infections can be life-threatening and include skin and bone infections and abscesses in organs such as the lungs, liver, and brain. The most common form of CGD is X-CGD, which only affects males and is caused by genetic mutations on the X chromosome. In addition to treating infections and prophylactic antibiotics, the only treatment option for CGD patients is to receive a bone marrow transplant from a healthy, matched donor. Bone marrow contains hematopoietic stem cells that can produce white blood cells. Bone marrow from healthy donors can produce functional white blood cells that effectively fight infection. However, it is difficult to determine a healthy matched bone marrow donor, and recovery after bone marrow transplantation involves complications such as implant-to-host disease (graft-to-host disease), infection risk, and transplant rejection.

　　Korn said: "Bone transplantation can certainly improve the patient's condition, but there are risks. We need to find a suitable donor." Patients should take 6-12 months of anti-immune rejection to avoid physical attacks. Outpatient bone marrow. In this new study, these researchers extracted hematopoietic stem cells from X-CGD patients and genetically modified them in the laboratory to correct the genetic mutations they carried. The patient’s own genetically modified hematopoietic stem cells have now been transplanted to the same patient. These hematopoietic stem cells are now normal and capable of producing white blood cells that can produce a variety of immune-enhancing chemicals. Although this method is a new method of X-CGD, Kohn used similar stem cell gene therapy to effectively treat more than 50 infants with severe and complex immune deficiency (also known as form). Pioneer use. Infant disease).

　　The lentivirus delivery system used in CGD gene therapy was developed and adjusted by the team of Professor Adrian Slasher of Great Ormond Street Hospital (GOSH) in the UK. Nine patients were 2 to 27 years old. The Great Ormond Street Hospital received four treatments and the United States received five treatments. In this new study, two patients died within three months of receiving treatment because they were severely infected before receiving gene therapy. After receiving stem cell gene therapy, 7 surviving patients were followed up for 12-36 months. None of them had new CGD-related infections, and 6 of them were able to stop using conventional preventive antibiotics.

　　Korn said: “No patient will have complications that are usually observed in donor cells. The treatment results are equal to or better than those obtained with donor bone marrow transplantation.”

　　Kohn is the co-founder of the biotechnology company Orchard Therapeutics. The company has obtained this X-CGD research gene therapy right from the French Genethon R&D Center. We will work with US and European regulatory agencies to conduct larger clinical trials to further study this innovative treatment. Mr. Korn said that his goal is to obtain regulatory approval to commercialize this therapy.

　　Kohn and his colleagues plan to develop similar treatments for other forms of CGD. Korn said: "In addition to CGD, there are other diseases caused by blood cell protein deficiency, which can be treated with similar methods."