Duchenne Muscular Dystrophy (DMD) is a severe childhood form of muscular dystrophy. Both the severe form and its milder form of Becker Muscular Dystrophy (BMD) are caused by the mutation of dystrophin gene. Different ...Duchenne Muscular Dystrophy (DMD) is a severe childhood form of muscular dystrophy. Both the severe form and its milder form of Becker Muscular Dystrophy (BMD) are caused by the mutation of dystrophin gene. Different from some other genetic diseases such as hemophilia that can be treated by replacement therapy, there is no effective therapy for muscular dystrophy in conventional medication. Gene editing technology from the recently developed engineered nucleases such as TALENs has been successfully employed in genome modification of a variety of species, and will be applied in gene therapy of selected human diseases. The genetic basis of DMD and BMD indicates that DMD is a good target for gene therapy through returning the reading frame of dystrophin gene. Gene therapy strategies described here may apply to many other genetic diseases. Wider application of TALENs in gene therapy have the potential to dramatically prolong the lifespan of individuals with genetic diseases.展开更多
Post-exposure prophylaxis(PEP)for leprosy is administered as one single dose of rifampicin(SDR)to the contacts of newly diagnosed leprosy patients.SDR reduces the risk of developing leprosy among contacts by around 60...Post-exposure prophylaxis(PEP)for leprosy is administered as one single dose of rifampicin(SDR)to the contacts of newly diagnosed leprosy patients.SDR reduces the risk of developing leprosy among contacts by around 60%in the first 2–3 years after receiving SDR.In countries where SDR is currently being implemented under routine programme conditions in defined areas,questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M.tuberculosis strains circulating in these areas.This issue has not been addressed in scientific literature to date.To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis,a meeting was convened with tuberculosis(TB)and leprosy experts.The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of(multi)drug-resistance in M.tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy.They concluded that SDR given to contacts of leprosy patients,in the absence of symptoms of active TB,poses a negligible risk of generating resistance in M.tuberculosis in individuals and at the population level.Thus,the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M.tuberculosis.展开更多
Background: Leprosy control achieved dramatic success in the 1980s–1990s with the implementation of short course multidrug therapy,which reduced the global prevalence of leprosy to less than 1 in 10000 population.How...Background: Leprosy control achieved dramatic success in the 1980s–1990s with the implementation of short course multidrug therapy,which reduced the global prevalence of leprosy to less than 1 in 10000 population.However,a period of relative stagnation in leprosy control followed this achievement,and only limited further declines in the global number of new cases reported have been achieved over the past decade.Main text In 2016,major stakeholders called for the development of an innovative and comprehensive leprosy strategy aimed at reducing the incidence of leprosy,lowering the burden of disability and discrimination,and interrupting transmission.This led to the establishment of the Global Partnership for Zero Leprosy(GPZL)in 2018,with partners aligned around a shared Action Framework committed to achieving the WHO targets by 2030 through national leprosy program capacity-building,resource mobilisation and an enabling research agenda.GPZL convened over 140 experts from more than 20 countries to develop a research agenda to achieve zero leprosy.The result is a detailed research agenda focusing on diagnostics,mapping,digital technology and innovation,disability,epidemiological modelling and investment case,implementation research,stigma,post exposure prophylaxis and transmission,and vaccines.This research agenda is aligned with the research priorities identified by other stakeholders.Conclusions: Developing and achieving consensus on the research agenda for zero leprosy is a significant step forward for the leprosy community.In a next step,research programmes must be developed,with individual components of the research agenda requiring distinct expertise,varying in resource needs,and operating over different timescales.Moving toward zero leprosy now requires partner alignment and new investments at all stages of the research process,from discovery to implementation.展开更多
文摘Duchenne Muscular Dystrophy (DMD) is a severe childhood form of muscular dystrophy. Both the severe form and its milder form of Becker Muscular Dystrophy (BMD) are caused by the mutation of dystrophin gene. Different from some other genetic diseases such as hemophilia that can be treated by replacement therapy, there is no effective therapy for muscular dystrophy in conventional medication. Gene editing technology from the recently developed engineered nucleases such as TALENs has been successfully employed in genome modification of a variety of species, and will be applied in gene therapy of selected human diseases. The genetic basis of DMD and BMD indicates that DMD is a good target for gene therapy through returning the reading frame of dystrophin gene. Gene therapy strategies described here may apply to many other genetic diseases. Wider application of TALENs in gene therapy have the potential to dramatically prolong the lifespan of individuals with genetic diseases.
基金supported by Novartis Foundation as coordinator of the LPEP project and hosted by the Netherlands Leprosy Relief,one of the ILEP partners involved in the LPEP project.
文摘Post-exposure prophylaxis(PEP)for leprosy is administered as one single dose of rifampicin(SDR)to the contacts of newly diagnosed leprosy patients.SDR reduces the risk of developing leprosy among contacts by around 60%in the first 2–3 years after receiving SDR.In countries where SDR is currently being implemented under routine programme conditions in defined areas,questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M.tuberculosis strains circulating in these areas.This issue has not been addressed in scientific literature to date.To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis,a meeting was convened with tuberculosis(TB)and leprosy experts.The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of(multi)drug-resistance in M.tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy.They concluded that SDR given to contacts of leprosy patients,in the absence of symptoms of active TB,poses a negligible risk of generating resistance in M.tuberculosis in individuals and at the population level.Thus,the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M.tuberculosis.
文摘Background: Leprosy control achieved dramatic success in the 1980s–1990s with the implementation of short course multidrug therapy,which reduced the global prevalence of leprosy to less than 1 in 10000 population.However,a period of relative stagnation in leprosy control followed this achievement,and only limited further declines in the global number of new cases reported have been achieved over the past decade.Main text In 2016,major stakeholders called for the development of an innovative and comprehensive leprosy strategy aimed at reducing the incidence of leprosy,lowering the burden of disability and discrimination,and interrupting transmission.This led to the establishment of the Global Partnership for Zero Leprosy(GPZL)in 2018,with partners aligned around a shared Action Framework committed to achieving the WHO targets by 2030 through national leprosy program capacity-building,resource mobilisation and an enabling research agenda.GPZL convened over 140 experts from more than 20 countries to develop a research agenda to achieve zero leprosy.The result is a detailed research agenda focusing on diagnostics,mapping,digital technology and innovation,disability,epidemiological modelling and investment case,implementation research,stigma,post exposure prophylaxis and transmission,and vaccines.This research agenda is aligned with the research priorities identified by other stakeholders.Conclusions: Developing and achieving consensus on the research agenda for zero leprosy is a significant step forward for the leprosy community.In a next step,research programmes must be developed,with individual components of the research agenda requiring distinct expertise,varying in resource needs,and operating over different timescales.Moving toward zero leprosy now requires partner alignment and new investments at all stages of the research process,from discovery to implementation.
