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Faster-Acting, Longer-Lasting Gene Therapy for RP Shows Promise
Long before the launch of gene therapy studies that have restored vision for patients with Leber congenital amaurosis (LCA), Foundation-funded researchers were hard at work refining their gene delivery technologies for future therapies to treat a broad spectrum of retinal degenerative diseases. They recognized that for certain retinal conditions, they needed to develop gene delivery technologies that: 1) worked more quickly; 2) provided a more sustained effect; and 3) worked more efficiently and effectively in photoreceptors.

Their proactive efforts are now paying off.

A Foundation-funded research team, which included investigators from China, Italy, and The Jackson Laboratory in Maine, recently reported impressive success in preserving vision in a lab study of gene therapy for mice with an aggressive form of retinitis pigmentosa (RP) caused by variations in the gene PDE6B. The therapy has been effective for more than six months. Treating the PDE6B-mutant mouse model is important, because as much as five percent of people with recessive RP have mutations in PDE6B.

Ji-jing Pang, M.D., Ph.D., a key team member from the University of Florida, says that the team is planning to evaluate the treatment in a canine study. Getting good results in a large animal model study is a critical step in moving the treatment into a clinical trial.

The investigators used a newly developed adeno-associated virus serotype 8 (AAV8), a manmade therapeutic virus, for gene delivery — an approach that proved to be fast-acting, sustained, and effective. Previous attempts to treat this mouse model with AAV5 delivery were not as successful, because the retina degenerated before the treatment began to work.

“Serotype” is a term used to describe the structure of the adeno-associated virus. Different AAV structures have different therapeutic properties. AAV8 has shown to be particularly effective in delivering corrective genes to photoreceptors. In this study, the investigators made a special modification to the outer structure of the AAV8 to further enhance the strength and speed of the therapy.

“When it comes to gene therapies, one size does not fit all,” says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness. “We need to tailor the delivery mechanism to fit the targeted disease and the cells to be treated. AAV2 has worked well for treating LCA in animals and humans. A completely different type of virus, a lentivrus developed by Oxford Biomedica, is showing promise for Stargardt disease, Usher syndrome, and age-related macular degeneration. The Foundation is also investing in nanoparticle research which may be effective for delivering corrective genes to the retina.”

Oxford Biomedica, a gene therapy developer in the United Kingdom, has received regulatory approval to begin a Phase I clinical trial of lentiviral gene therapy for Stargardt disease. The company plans to start the trial in mid-2011 at Oregon Health and Science University (Portland, Oregon) and Centre Hospitalier Nationale D’Opthalmologie des Quinze-Vingts (Paris, France). Their Phase I clinical trial of lentiviral gene therapy for the wet form of age-related macular degeneration is underway at Johns Hopkins University Hospital (Baltimore, Maryland).

Applied Genetic Technologies Corporation AGTC, a gene therapy company in Central Florida, has a Phase I clinical trial of an AAV-based gene therapy underway for LCA, and is developing gene therapies for achromatopsia (day blindness) and retinoschisis.

Both Oxford’s and AGTC’s therapies were made possible by preclinical research funded by the Foundation




研究者使用一种新开发的腺相关病毒8型(AAV8),一人为治疗病毒,基因传递 - 这种方式被证明是快速行动,持续,有效的。以前曾试图处理这个AAV5交付小鼠模型并没有那样成功,因为之前的治疗视网膜退化开始工作。

“轮状病毒”是用来描述腺相关病毒结构的一个术语。不同的腺相关病毒的结构有不同的治疗特性。 AAV8已证明是特别在提供有效的纠正基因的光感受器。在这项研究中,研究人员还特意修改了AAV8外部结构,进一步提高强度和治疗的速度。

“当涉及到基因疗法,一大小不适合所有的,”斯蒂芬说,玫瑰,博士,首席研究人员,基础格斗失明。 “我们需要为客户定制的执行机制,以适应目标疾病和细胞进行治疗。 AAV2的行之有效的治疗在动物和人类的生命周期。一个完全不同类型的病毒,由牛津Biomedica开发出lentivrus,正在针对Stargardt病,Usher综合征,与年龄相关性黄斑变性的承诺。该基金会还投资于纳米研究,而这可能是提供纠正基因的视网膜有效。“

牛津Biomedica,一个在英国基因疗法开发,先后获得监管机构批准,开始第一期的慢病毒基因治疗Stargardt病的临床试验。该公司计划开始在2011年中期在美国俄勒冈保健科学大学(波特兰,俄勒冈州)和国立医学中心的德Opthalmologie德Quinze - Vingts(巴黎,法国)的审判。他们的第一阶段为年龄相关性黄斑变性湿性慢病毒基因治疗的临床试验是在约翰霍普金斯大学医院(巴尔的摩,马里兰州)正在进行中。


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