血友病,基因治疗 z-bo 2020-09-18 495

　　Ben Hugstad (Ben Hugstad) is a 12-year-old boy. He loves Taekwondo. He has practiced for 6 years and soon became a black belt in Taekwondo. It is hard to imagine that he suffers from severe hemophilia and his body cannot establish a blood clotting mechanism. In short, accidental falls and bruises can quickly lead to life-threatening.

　　Kimberly’s mother wakes up every three weeks and gives Ben an injection to help her clot in a short time. She said, "I never wanted to be a nurse."

　　These injections are very expensive, about US$2,500 per dose, but they are life-saving drugs. They prevent wounds from getting worse and becoming a disaster, and prevent spontaneous internal bleeding from leaking into joints and organs and causing serious problems. Currently, Ben is basically living a normal life, but he is learning Taekwondo and taking physical education courses like ordinary people. Kimberley said he never talked about the privacy of his condition, did not attend class, and did not use this as an excuse to miss the exam. At the end of the course, his whole body was injured.

　　Haugstad said: "He wants to do what he wants to do. We are testing to make it bleed for 6 weeks. It makes me very excited."

　　Mention is thankful that at some point in the future, Ben's injection every three weeks may be history. Through gene therapy, a modified virus carrying specific genetic instructions is injected into Ben's body, which allows him to clot on his own for several years or even a lifetime.

　　If his mother was a careless nurse, she might be happy to accept this treatment, but in fact Kimberly reacted very cautiously.

　　She said: "When he was born, we clearly heard that hemophilia would develop within three years," because she is still a member of the American Hematology Federation. I was very skeptical at the time. management. To some extent, she represents many parents, not just herself.

　　In fact, Kimberley has good reasons to understand this gene therapy. The idea of genetic treatment of hemophilia began in the 1980s. About 15 years ago, the first hemophilia patient volunteered for the test. So far, no gene therapy products have been launched. The clinical failure of genetic experiments and the high-profile safety hazards have caused a 180-degree change in people's attitudes towards gene therapy. This situation has not been cared about in previous hype. At the beginning of the 21st century, many important private investors withdrew their investments. Although it is now resurrected, there are still many problems that need to be resolved before Ben and the other 400,000 hemophiliacs rely on gene therapy. How long will these treatments last? How safe are they?

　　Gene therapy is definitely back. Venture capital companies have been reorganized and some have been opened to the public. Large pharmaceutical companies conduct research and development through corporate cooperation and strategic alliances. In a European country, the first product for a rare liver injury disease was approved in Europe. Another product can be used to treat severe hematological potassium syndrome.

　　Gene therapy for hemophilia lags far behind. So far, Baxter International (NYSE: BAX) is the only developer reporting clinical data.

　　After

　　Baxter, some companies knew the problem correctly. Their clinical progress will be carried out this year and next year, which will be a test of the entire gene therapy. In this gene therapy competition, hematopoietic diseases may be the most competitive.

　　S "The history of gene therapy will follow the story of hemophilia." James Wilson, head of gene therapy at the University of Pennsylvania, is a pioneer and most controversial figure in the field.

　　Judging from the current status of the company's next clinical trial, this story will open a new chapter. Seven teams have initiated hemophilia projects. They are the bases of large companies that protect their interests and small biological companies that plan or plan to cooperate with them. In addition, several scientific methods and strategies and destructive strategies have emerged in the fierce competition. Wilson, the scientific founder of the Washington Gene Therapy founding company, said: "I think the competition is good. Do you know who is the biggest beneficiary? Patients"

　　If this happens, it is a good thing. Even if the condition of today’s patients is much better than the previous or second generation, the results will continue for a long time. Until the 1980s, patients with hemorrhagic bleeding had to rush to the hospital to inject concentrated clotting factors or proteins. Hematopoietic A patients are injected with factor VIII, and type B is injected with factor IX.

　　If the bleeding is severe, it can be collected in the hospital for several weeks or months, and you should be very careful. To make matters worse, the injected factor comes from a donor's blood sample, which may cause hemophilia patients to develop AIDS or hepatitis C.

　　In 1982, scientists genetically modified factor IX to achieve the first breakthrough. Factor VII is two years later. Baxter's first recombinant factor VII product was approved by the FDA in 1992. These drugs completely changed the treatment of hemophilia. It not only eliminates the risk of blood contamination, but also paves the way for preventive treatment.

　　"Some young people don't remember bleeding," said Catherine Hay, chairman and chief scientific officer of the Philadelphia Children's Hospital, director of the Center for Cell and Molecular Therapy, and world-renowned spark therapy hematologist.

　　There are approximately 20,000 hemophiliacs in the UK, and an estimated 3,000 have hemophilia B. Although it is a chronic and controllable disease, it is still expensive and difficult to cure. According to a report by the National Hemophilia Foundation, approximately 60% of hemophilia patients suffer from serious illness. Since the content of coagulation factors in the blood is less than 1%, more blood needs to be drawn, and injections are required every 2-3 weeks. If the bleeding is slight, the frequency of treatment will be lower.

　　A small group of companies is researching protein alternative medicine to help patients who need less than once a week or fewer cycles or whose immune system cannot accept existing treatments. Yes. Alnylam Pharmaceuticals is developing short-lived RNA treatments.

　　These improvements have been completed, but even with “one-off” treatment, gene therapy is still looking for a lasting solution. Of course, it's not just hemophilia, this is the goal of many gene therapies. However, in fact, 30 years ago, he tried gene therapy for hemophilia, but the technology was not fully developed at that time, and he spent many years on treatment. For a long time, gene therapy sounded like a scientific novel. You would think of it as a dangerous microvirus, a small transportation vehicle, or a bacterial carrier in genetic engineering. Second, these tools are packaged by specific genetic instructions. It enters the stem cell, changes the DNA, and transmits these genetic instructions to all subsequent daughter cells.

　　This commitment is to understand very well what we know about genetic diseases, diseases caused by single errors or gene deletions, and formulate long-term solutions. In the 1990s, many founders appeared, but they soon faced technical challenges, especially in virus transmission.

　　"It takes a lot of time to compare which vector systems are easier to apply, easier to create, and safer," said Barry Carter, vice president of Biomarine Gene Therapy Regulations. statement. For hemophilia,

"" is the same, and for many reasons, the ideal target for gene therapy usually targets the disease. It is a single gene (caused by a single mutation). It is recessive (in order to cure it, you need to add genes instead of destroying them all). And only a few signs can be repaired. There are obvious changes in 5% of factors VII and XI in normal people.

　　 A simple blood test can be used to measure all the effects. Cystic fibrosis and hemophilia are the first diseases involved in gene therapy. Everything sounds ideal, but in fact, gene therapy is facing tremendous pressure. In 1999, scientists wrote: "If gene therapy does not work in a model of hemophilia, in which disease model does it work?"

　　 The first wave of friendship gene therapy trials in the late 1990s began. it is. High led the team to participate. She collaborated with Alameda to initiate gene therapy at Avigen headquarters.