科学家报告说，在FFB资助的转化研究的突出进展

凤凰涅盘

Scientists Report Outstanding Progress in FFB-Funded Translational Research
December 7, 2011 - An international team of retinal scientists funded by the Foundation’s Translational Research Acceleration Program (TRAP) convened in Las Vegas on November 29 to report on their progress over the last year in moving promising treatments and cures out of the lab and into clinical trials. From the discovery of new vision-saving compounds, to success in preclinical studies of emerging gene and stem cell therapies, to the identification of new disease-causing genes, progress in these clinically focused research efforts is occurring at an unprecedented rate.
“The impact of the five-year, $100 million commitment from Gordon Gund and other key TRAP investors is phenomenal,” says Dr. Stephen Rose, chief research officer, Foundation Fighting Blindness. “TRAP is enabling the world’s top retinal researchers to immediately capitalize on the latest breakthroughs and innovations in science. What used to take us decades to accomplish is now taking us a year or two. The science is there, and TRAP is enabling us to more effectively and expeditiously move the knowledge and technology into human studies.”
TRAP was launched originally in 2008 as a $10 million per year program, but the program’s investors, recognizing the expansion of clinical opportunities for retinal treatments, doubled their funding commitment in early 2011.
Collaboration is Key to Success
While aggressive funding is essential to scientific progress, advances are not made in a vacuum. Collaboration has been critical to accelerating the clinically focused efforts of TRAP-funded researchers. For example, earlier this year, Dr. Ed Stone, director of the Carver Genetics Lab at the University of Iowa, found that defects in the MAK gene are a common cause of retinitis pigmentosa (RP) among people with Ashkenazi (Eastern European Jewish) descent. Using stem cell technologies being perfected by scientists like Dr. David Gamm at the University of Wisconsin–Madison, Dr. Stone and his colleague Dr. Budd Tucker were able to better evaluate how defects in the MAK gene cause vision loss and, at the same time, explore potential therapies for MAK-based RP. In turn, Dr. Gamm is using gene therapy technology developed in other labs to correct genetic defects in his emerging stem cell treatments — stem cells derived from skin or blood — so they can be used in a future retinal cell transplantation clinical trial.
“The cross pollination occurring among TRAP investigators is pervasive and invaluable. They can accomplish so much more, and at a faster pace, by sharing resources and knowledge. Everybody wins through open collaboration, especially the patients,” says Dr. Rose.
Gene Discoveries Open the Door to New Treatments, Clinical Trials
In 2011, both Dr. Stone and Dr. Stephen Daiger of the University of Texas Health Science Center at Houston used a highly efficient, state-of-the-art gene screening technology known as whole-exome sequencing to identify new genetic defects that cause retinal degenerative disease.
Dr. Stone’s work in finding MAK as a link to autosomal recessive RP (arRP) was recognized as a critical advancement, because it was found to be the cause of retinal disease in 20 of his previously undiagnosed patients and will undoubtedly be linked to arRP in dozens of other people around the United States and the world.
Dr. Daiger’s discovery of RPE65’s link to autosomal dominant RP (adRP) and the identification of other genetic regions linked to adRP and X-linked RP were important steps forward in diagnosing several affected families and providing targets for future treatments.
Through their genetic testing services, Drs. Stone and Daiger significantly expanded their collections of patient DNA and natural history information, which will not only provide new diagnoses for families, but also help identify candidates for forthcoming clinical trials.
Dr. Stone reports that his nonprofit genetic lab can now screen for 24 retinal degenerative diseases (50 genes), including: arRP, Leber congenital amaurosis (LCA), Stargardt disease and Usher syndrome. To date, the lab has found disease-causing genes in approximately 4,500 families from 50 states in the United States and 60 countries.
Advancements in Stem Cell Treatments on Multiple Fronts
Over the past year, Dr. Thomas Reh of the University of Washington continued his pioneering work in developing transplantation strategies for retinal disease treatments derived from embryonic stem cells (hESC). His goal was to produce viable retinal cells and successfully transplant them into various small and large animal models. This strategy provides potential for saving and restoring vision in people affected by a wide range of retinal conditions, including those with the most advanced vision loss.
Dr. Reh was successful in producing large quantities of viable retinal cells that survive when transplanted, and in some mouse models of retinal disease, they restored some visual function. His next step is to evaluate and perfect this strategy in larger animal models; doing so will position him well to gain FDA approval for a clinical trial.
As mentioned previously, Dr. David Gamm is using an innovative technique to derive stem cells from a patient’s skin or blood. Known as induced pluripotent stem cells (iPSC), they have many of the advantages of embryonic stem cells, namely flexibility and ease of replication. But the patient serves as his or her own cell donor; embryos are not needed. Over the past year, Dr. Gamm successfully derived stem cells from the skin of a patient with a retinal disease known as gyrate atrophy, and subsequently used gene therapy to correct the genetic defect in the cell. He was also successful in generating sheets of iPSC that might be used in a future transplantation clinical trial. His next step is to evaluate iPSC transplantation in animal models.
As was also mentioned, several researchers from around the world, such as Dr. Stone, are using iPSC as a method for studying retinal disease “in a dish” and testing the safety and efficacy of potential drugs and other treatment modalities.

凤凰涅盘

1# 凤凰涅盘
Screening Drugs, Molecules and Plant Extracts to Find Vision-Saving Treatments
Using innovative screening technologies, four TRAP-funded investigators are each on a quest to find compounds that can preserve vision for people affected by a wide range of retinal diseases.
Dr. Bärbel Rohrer of the Medical University of South Carolina and her team previously screened 50,000 compounds to identify those that enhanced mitochondrial function. Mitochondria are the energy centers of all cells, including photoreceptors, and disease often compromises their function. Dr. Rohrer’s research indicates that compounds which enhance or preserve mitochondrial function will likely also halt vision loss.
After identifying two promising treatment candidates, Dr. Rohrer has been working to better understand what features of the compounds are making them protective, and producing enhanced, second generation versions of them for advancement into human studies.
Dr. Don Zack of the Wilmer Eye Institute at Johns Hopkins University previously screened a library of 5,000 FDA-approved drugs and compounds to identify those that save and protect retinal cells. He found that an anti-cancer drug, sunititib, as a promising neuroprotective candidate. He also discovered that a protein called stanniocalcin-1 (STC-1) has strong protective properties. He continues to perform studies of both of these agents to better understand their mechanisms of action and potential use in clinical trials.
Dr. Zack is also collaborating with Drs. Reh and Gamm as well as Dr. Michael Young of Schepens Eye Research Institute, Massachusetts Eye and Ear, to develop stem cell models of retinal disease for testing additional potential therapies.
Dr. Thierry Lêveillard of the Institut de la Vision, INSERM, in Paris previously screened 800 plant extracts to evaluate their potential for protecting cones, the photoreceptors that provide the vision most critical to our daily activities. The most promising extract proved to be Uvaria chamae, a large, fruit-bearing shrub in Africa. He is now working to identify the molecule(s) in the plant that are protective, with the goal of developing a treatment from them.
Dr. Matt LaVail of the University of California, San Francisco, is a recognized leader in the use of animal models to identify and study agents that may be neuroprotective for the degenerating retina. In addition to studying several of his own proteins and molecules, Dr. LaVail has collaborated with Drs. Rohrer and Zack to evaluate their treatment candidates in his rodent models. He also performed animal studies of valproic acid — an FDA-approved drug in FFB-funded clinical trials for adRP — to help determine which forms of RP would be most amenable to the treatment approach.
TRAP Makes Strong Commitment to Gene Therapies
Leveraging the success of the first-ever clinical trials of gene therapy for retinal degenerative disease — studies that have restored some vision in 40 children and young adults who were virtually blind from LCA — the Foundation recently announced TRAP-based support of $8.25 million for six, three-year gene therapy grants. To be eligible for the funding, each of the recipients was required to submit a plan indicating how they would be ready to seek authorization from the FDA to launch a clinical trial within three years. The projects include gene therapies for: two forms of LCA (RPGRIP1 and GUCY2D), choroideremia, adRP, X-linked retinoschisis (XLRS), a nanoparticle gene delivery system for delivering larger genes, and an optogenetic therapy to harness and revive a variety of retinal cell types for vision.
Dr. Jeff Chulay, chief medical officer of Applied Genetic Technologies Corporation, discussed his FFB-funded collaboration with Oregon Health & Sciences University in developing a gene therapy for XLRS. He noted that the treatment has the opportunity to benefit as many as 35,000 affected people in the United States and Europe. He said that without TRAP funding, the final preclinical steps in development of the gene therapy, including optimization of the viral delivery system and a final large animal study, would not be possible.
Earlier this year, Dr. John Flannery of the University of California, Berkeley, successfully used gene therapy to empower ganglion cells of the retina to respond to light in a mouse model of retinal degeneration in which all photoreceptors had been lost. While not a TRAP-funded investigator, he provided an overview of his work, the growing and promising field of optogenetics, and a TRAP-funded cone-restoration effort being conducted at the Institut de la Vision in Paris.
Dr. William Hauswirth of the University of Florida, a world leader in gene delivery technology development and a TRAP-funded investigator working on a gene therapy for adRP, discussed the current status of gene therapy research for retinal degenerative diseases. He noted that gene therapies have been successful in at least 17 preclinical disease models, and that clinical trials for six different diseases — LCA, arRP, choroideremia, Usher syndrome, Stargardt disease and wet age-related macular degeneration — are underway. (The Usher syndrome trial is scheduled to begin before the end of 2011.)
TRAP Supports Clinical Advancement of Valproic Acid for RP
Earlier in 2011, FFB launched a three-year, 90-participant human study of valproic acid, a drug already FDA-approved for seizure disorders, in its National Eye Evaluation Research network. Dr. Rose discussed how TRAP funding was essential in determining which patients should be enrolled in the trial. Previous lab studies and clinical observations had shown that valproic acid was an excellent candidate for slowing vision loss in people with adRP. However, there was little data showing the drug’s effect on people with arRP. In subsequent TRAP-funded lab studies, scientists determined that valproic acid did not preserve vision in arRP. As a result of these findings, only people with adRP are being enrolled.
Dr. Rose also noted that the valproic acid trial is being expanded from two sites — the University of Utah and Retina Foundation of the Southwest — to as many as five sites in an effort to increase patient enrollment.
TRAP-Funded Clinician-Scientist to Provide Critical Clinical Trial Support
One of the biggest challenges for researchers conducting clinical trials for retinal degenerative disease treatments is developing and selecting outcome measures that can indicate whether or not the therapy is working. In many retinal conditions, traditional study endpoints, such as visual acuity and visual field, will not give a complete picture of the treatment’s efficacy.
Dr. Hendrik Scholl of the Wilmer Eye Institute at Johns Hopkins University — an up-and-coming clinician-scientist and recipient of a TRAP career development award — is developing high-resolution imaging and functional mapping techniques to more effectively evaluate the efficacy of potential therapies. In addition to publishing several peer-reviewed research papers on his innovations, Dr. Scholl will be using these imaging and mapping tools in early-stage clinical trials of treatments for LCA, RP and Stargardt disease.
Staying Tuned
For more information on advancements and breakthroughs being made by TRAP-funded researchers, register online at www.FightBlindness.org to receive the Foundation’s newsletters and news announcements.
Also, several TRAP investigators will be presenting at the 2012 VISIONS Conference, being held June 28-July 1 in Minneapolis. Registration for the event is now open.

凤凰涅盘

2# 凤凰涅盘

12月7日，2011年 - 国际由该基金会的转化研究加速计划（TRAP）资助视网膜科学家小组召开11月29日以报告在过去一年中对自己的进步，在移动实验室的有前途的治疗和治愈，并进入在拉斯维加斯临床试验。从发现新的视野节能化合物，在新兴的基因和干细胞疗法的临床前研究的成功，新的致病基因的鉴定，这些临床重点研究工作的进展情况是发生在以前所未有的速度。
“五年，从戈登冈德和其他关键陷阱投资者承诺的100万美元的影响是惊人的，”斯蒂芬博士说​​：玫瑰，首席研究人员，基金会战斗失明。 “陷阱是使世界顶级的视网膜的研究人员能够立即利用最新的突破和科学创新。是什么把我们几十年来完成，现在我们一年或两年。科学和陷阱使我们更有效和更迅速地转移到人体研究的知识和技术。“
陷阱在2008年推出最初为1000万美元，每年计划，但该计划的投资者，认识到扩大视网膜治疗的临床机会，他们在2011年年初的资金承诺了一倍。
协作是成功的关键
虽然积极的资金是必不可少的科学进步，进步是不是在真空中。协作已经加快陷阱资助的研究人员在临床上集中精力，努力至关重要。例如，今年早些时候，埃德斯通，在美国爱荷华大学卡弗遗传学实验室主任，博士发现，在麦基因缺陷是共同的事业，与德系的人之间的视网膜色素变性（RP）（东欧犹太人）血统。利用干细胞在威斯康星 - 麦迪逊，斯通博士和他的同事布塔克博士大学的科学家像大卫博士Gamm完善的技术，能够更好地评估在麦基因引起视力减退如何缺陷，并在同一时间，探讨麦基于RP的潜在疗法。反过来，Gamm博士是使用在其他实验室开发的，以纠正在其新兴的干细胞治疗遗传缺陷 - 从皮肤或血液干细胞 - 使他们能够在未来的视网膜细胞移植的临床试验中使用的基因治疗技术。
“陷阱调查之间发生异花授粉，是普遍的和宝贵的。他们能完成这么多，并以更快的步伐，通过资源共享和知识。罗斯博士说：“每个人都通过开放协作，特别是患者赢得。
基因的发现打开大门，新的治疗方法，临床试验
2011年，在休斯敦的得克萨斯大学健康科学中心大学博士石和博士斯蒂芬Daiger使用了一个高效的，国家的最先进的基因筛选技术被称为全外显子组测序，以确定新的遗传缺陷，导致视网膜退化疾病。
博士石作为一个常染色体隐性遗传RP（ARRP）的链接中找到麦的工作被认可作为一个重要的进步，因为它被认为是视网膜疾病的原因，他以前确诊的患者20，无疑将与ARRP在数十名美国和世界各地的其他人。
博士Daiger发现RPE65的链接，以常染色体显性遗传RP（ADRP），并确定与ADRP和X -连锁RP其他遗传地区的重要步骤，在诊断一些受影响的家庭，并为未来的治疗目标。
通过基因检测服务，博士。石和Daiger显著扩大病人的DNA和自然历史信息，这将不仅为家庭提供的新的诊断自己的藏品，但也为即将进行的临床试验帮助确定候选人。
博士石的报告，他的非营利性的遗传实验室现在可以屏幕为24视网膜变性疾病（50个基因），包括：ARRP，莱伯先天性黑蒙（LCA），Stargardt病和Usher综合征。到目前为止，实验室已发现约4500名来自美国和60个国家的50个州的家庭中的致病基因。
在多方面的干细胞治疗的进步
在过去的一年，华盛顿大学的托马斯博士REH继续他来自胚胎干细胞（胚胎干细胞）的视网膜疾病治疗的移植战略发展的开创性工作。他的目标是可行的视网膜细胞，并成功地移植到各种小型和大型的动物模型。这一战略提供了保存和恢复视力由视网膜的条件，包括与最先进的视力减退的广泛影响的人的潜力。
REH博士是成功可行的生存时，移植的视网膜细胞的大量生产，并在一些视网膜疾病的小鼠模型，他们恢复了一些视觉功能。他的下一步是评估和完善这一战略在更大的动物模型，这样做将使他获得美国FDA批准进行临床试验。
如前所述，博士大卫Gamm使用的是创新技术，从病人的皮肤或血液中获得的干细胞。被称为诱导多能干细胞（IPSC），他们有许多胚胎干细胞，即灵活性和易于复制的优势。但病人作为他或她自己的细胞捐献的胚胎并不需要。 Gamm博士在过去的一年，成功来自病人的皮肤干细胞被称为回旋萎缩的视网膜疾病，并随后利用基因疗法来纠正在细胞中的遗传缺陷。他还成功的IPSC的产生可能在未来移植的临床试验中使用的表。他的下一步是评估IPSC移植动物模型。
还提到，一些研究人员来自世界各地，如博士石，正在使用IPSC为研究视网膜疾病的“菜”和测试的安全性和潜在的药物和其他治疗方法的疗效的方法。
筛选药物，分子和植物提取物的视觉保存治疗
使用创新的筛选技术，有4个陷阱资助的调查是每一个任务找到的化合物，可以保留通过广泛的视网膜疾病影响的人的视力。
南卡罗来纳医科大学Bärbel Rohrer博​​士和她的团队先前筛选50000化合物，以找出那些能够增强线粒体的功能。线粒体是所有细胞，包括光感受器的能源中心，疾病往往会影响其功能。 Rohrer博​​士的研究表明，提高或维持线粒体功能的化合物也有可能会阻止视力减退。
两个前途的治疗候选人确定后，Rohrer博​​士一直致力于更好地理解什么化合物的特点是他们的保护，为人类研究的进步和生产的增强，他们的第二代版本。
扎克在约翰霍普金斯大学Wilmer眼科研究所博士唐以前筛选5000 FDA批准的药物和化合物库，以确定这些，挽救和保护视网膜细胞。他发现，抗癌药物，sunititib，是一个很有前途的神经候选人。他还发现，一种蛋白质称为斯钙- 1（STC - 1）具有较强的防护性能。他继续执行这两个代理的研究，以更好地了解他们的行动，并在临床试验中的潜在用途的机制。
扎克博士是与DRS。 REH和Gamm以及博士迈克尔杨斯格本斯眼科研究所，马萨诸塞州眼耳，开发用于测试其他潜在的治疗视网膜疾病的干细胞模型。
利在巴黎INSERM的，研究所的愿景，Lêveillard以前筛选了800个植物提取物保护锥，感光器，提供了最关键的愿景我们的日常活动，以评估他们的潜力。最有前途的提取物被证明是Uvaria chamae，果大，轴承在非洲灌木。他现在是从他们的治疗发展的目标，在植物保护工作，以确定分子（S）。
马特LaVail博士，美国加州大学，旧金山，是一个公认的领导者使用的动物模型，以确定和研究代理可能变质视网膜神经。除了学习一些自己的蛋白质和分子，博士LaVail合作与DRS。 Rohrer和Zack在他的啮齿动物模型，以评估其治疗候选人。他还进行了动物实验研究丙戊酸 - ADRP FFB资助的临床试验FDA批准的药物 - 以帮助确定RP的形式将是最适合的治疗方法。
陷阱使强的基因疗法的承诺
利用的视网膜退行性疾病成功的基因疗法首次临床试验 - 研究，已经恢复了一些在40儿童和年轻的成年人视力几乎从LCA的盲目 - 基金会最近宣布陷阱 - 基于六8.25亿美元支持三年的基因治疗补助。要对资金的资格，每个收件人被要求提交一份计划，说明他们将如何准备寻求从美国FDA批准在三年内推出一项临床试验。这些项目包括基因疗法两种形式LCA（RPGRIP1和GUCY2D），无脉络膜，ADRP，X -连锁视网膜（XLRS），纳米粒子的基因传递系统提供更大的基因，和optogenetic治疗，利用和恢复各种视网膜视觉细胞类型。
俄勒冈卫生科学大学的杰夫Chulay博士，应用基因技术公司的首席医疗官，讨论他的FFB资助的合作，在发展为XLRS基因治疗。他指出，治疗中受益的机会，在美国和欧洲多达35000受灾群众。他说，没有陷阱资金，在基因治疗的发展，包括病毒传递系统的优化和最后的大型动物的研究，临床前的最后步骤，不会有可能。
今年早些时候，约翰弗兰纳博士加州大学伯克利分校，成功利用基因疗法使视网膜神经节细胞在视网膜变性小鼠模型中，所有的光感受器已经失去响应光。他虽然不是一个陷阱资助的调查，他的工作提供了一个概述，光遗传学的不断发展和前途的领域，并在巴黎研究所DE LA视觉陷阱资助的锥恢复工作正在进行。
佛罗里达大学的威廉Hauswirth博士，世界领先的基因传递技术的发展和陷阱资助的调查，为ADRP基因治疗的工作，讨论了视网膜变性疾病的基因治疗研究的当前状态。他指出，基因疗法已成功在至少17个临床前疾病模型，并为6个不同的疾病的临床试验 - 生命周期，ARRP，无脉络膜，Usher综合征，Stargardt病和湿性年龄相关性黄斑变性 - 正在进行。 （Usher综合征审判定于2011年底前开始。）
陷阱支持RP丙戊酸的临床地位
在2011年早些时候，FFB推出一项为期三年，90参与人类的丙戊酸的研究，已经获得FDA批准在全国眼科评价研究网络，为癫痫的药物。博士玫瑰讨论的TRAP资金是如何确定哪些患者应在参加审判至关重要。以前的实验室研究和临床观察表明，丙戊酸是一个出色的候选人，减缓ADRP人视力减退。然而，有少的数据显示ARRP人对药物的效果。在随后的陷阱，资助实验室研究中，科学家们确定丙戊酸没有保留ARRP的视野。由于这些研究结果的结果，只有人民才是与ADRP被录取。
博士罗斯还指出，丙戊酸试验正在扩大从两个站点 - 犹他州立大学和西南视网膜基金会 - ，多达五，努力提高病人的招生网站。
TRAP -资助的临床医生，科学家，提供了关键的临床试验支持
视网膜变性疾病的治疗进行临床试验的研究人员面临的最大挑战之一是开发和选择的结果的措施，可以表明治疗与否是工作。视网膜在许多条件下，如视力和视野，传统的研究终点，不会给一个完整的画面治疗的疗效。
在约翰霍普金斯大学Wilmer眼科研究所 - 和未来的临床医生，科学家和陷阱的职业发展奖获得者 - 亨德里克绍尔博士正在开发高分辨率成像和功能映射技术，更有效地评估潜在的疗效疗法。除了出版的几个同行审查了他的创新研究论文，绍尔博士将使用在治疗早期阶段的临床试验的生命周期，RP和Stargardt病这些成像和制图工具。
保持调谐
由陷阱资助的研究人员取得的进步和突破的更多信息，登记在www.FightBlindness.org网上收到基金会的通讯和新闻公告。
此外，有几个陷阱侦查员将提出在2012年VISIONS会议正在举行六月，28日7月1日在明尼阿波利斯。事件注册现已开放。

passway

多谢楼主分享·~~

罗兰德尼奥

陷阱。。。 啥意思

rwmlau2004

TRAP-Funded <<< 翻译上的问题
TRAP 应该是一个基金简称
翻译后变成 “陷阱”

flyeagle

谢谢分享！

福娃晶晶

谢谢！综合性的好消息！

洁傲不逊

November, 28, 2011 - Foundation-funded researchers from the University of Florida have taken a major step forward in the development of a vision-restoring, gene-replacement therapy for people with Leber congenital amaurosis (LCA) caused by mutations in the gene GUCY2D.  They demonstrated that efficacy of the treatment in a mouse model of the condition was sustained for a year, a significant improvement over earlier studies in which the treatment’s effect lasted three months. The investigators believe that given these latest results, a similar treatment could last for several years or possibly a lifetime in humans.

越来越多的RP致病基因被攻克。 战友们，希望就在前方。

rwmlau2004

9# 洁傲不逊

原理上只要可以攻克某一类基因
其它致病基因都可以可用同一个原理攻克