See Inside <\/p>\n
History explains why people with the malady, and their physicians, are cautious to believe that a cure is in sight <\/p>\n
HEATHER VAN UXEM LEWIS <\/p>\n
In 2011, a remarkable study in the New England Journal of Medicine detailed the successful treatment of six adults with haemophilia B, which is caused by a deficiency in the coagulation protein known as factor IX. All of the participants were able to eliminate or reduce the frequency of clotting-factor-replacement injections the current standard treatment for the disease after their livers began producing functional levels of factor IX. The experimental therapy came in the form of an adeno-associated virus (AAV) carrying a gene that encodes instructions for production of normal levels of human factor IX. Three trials of AAV-mediated gene transfer in patients with haemophilia B are ongoing, with high expectations. <\/p>\n
After more than 20 years of research on gene transfer, it is a promising time for haemophilia therapies. It now seems likely that a single-dose treatment for haemophilia B using an AAV or another gene-transfer technique will be a viable option for many people in the next decade or two. <\/p>\n
Yet haemophilia researchers are not inclined to speak enthusiastically of a cure. Part of that caution comes from recognition that there are still problems to solve. For example, some 40% of people with haemophilia B would find no refuge in an AAV treatment because they produce antibodies that attack and neutralize this virus. <\/p>\n
And even if that problem were solved, the treatment would apply only to those with haemophilia B. The more common form of the condition, haemophilia A, stems from a deficit in another protein factor VIII and the gene for that protein is a more difficult target. Regardless of the type of haemophilia, researchers remain hesitant about gene therapy owing to the unresolved ethical issues that arose decades ago. <\/p>\n
The unfettered optimism that characterized the early years of gene-therapy research came to a screeching halt in 1999, when 18-year-old Jesse Gelsinger died in a phase I clinical trial at the University of Pennsylvania in Philadelphia. Gelsinger had undergone an experimental gene transfer for his otherwise treatable metabolic disorder. His death, along with a series of other harmful events in early gene-therapy trials for a variety of diseases, threatened the whole field. <\/p>\n
Haemophilia specialists who were engaged in gene-transfer studies were more guarded than most of that era's self-proclaimed gene doctors. The source of their reserve goes beyond the cautious optimism that characterized such research after 1999; it is grounded instead in the long and troubled experience that the haemophilia community has had with technological fixes. <\/p>\n
By the late 1970s, a therapeutic revolution had transformed haemophilia from an obscure hereditary malady into a manageable disease. But the glory of this achievement was tragically short-lived. The same clotting-factor-replacement therapies that delivered a degree of normality to the lives of people with haemophilia brought unexpected and fatal results: tens of thousands of people with haemophilia were diagnosed with transfusion-related HIV\/AIDS in the 1980s and with hepatitis C virus (HCV) in the 1990s. <\/p>\n
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Gene Therapys Haemophilia Promise Is Tempered by Memories of Past Tragedies<\/a><\/p>\n","protected":false},"excerpt":{"rendered":" See Inside History explains why people with the malady, and their physicians, are cautious to believe that a cure is in sight HEATHER VAN UXEM LEWIS In 2011, a remarkable study in the New England Journal of Medicine detailed the successful treatment of six adults with haemophilia B, which is caused by a deficiency in the coagulation protein known as factor IX. All of the participants were able to eliminate or reduce the frequency of clotting-factor-replacement injections the current standard treatment for the disease after their livers began producing functional levels of factor IX Continue reading