加拿大渥太华医院研究所开始新的基因治疗研究

雪山飞狐

Ottawa researcher awarded $1.4M to lead international team developing gene therapy for retinal blindness
Mar 08, 2010
Leading vision researchers from Canada and the U.S. are embarking on a five-year, $1.4M collaborative project to develop a new gene therapy to prevent blindness due to retinal diseases. Canada’s largest private charity for vision research, the Foundation Fighting Blindness, is partnering with the Canadian Institutes of Health Research to fund the program. The research team includes six scientists led by Dr. Catherine Tsilfidis, Senior Scientist at the Ottawa Hospital Research Institute and Associate Professor in the Faculty of Medicine at the University of Ottawa.

“The goal of this project is to begin testing a new gene therapy in patients, who are losing their vision due to retinal disease, by the end of five years,” said Dr. Tsilfidis. “This is an ambitious goal, but we think it is achievable. Our results so far have been very encouraging and our team has the dedication and the experience to bring this into the clinic quickly.”

The retina is the inner lining of the eye that is responsible for sensing light. Millions of people in North America suffer from diseases that involve the retina, such as retinitis pigmentosa, glaucoma, retinal ischemia and age-related macular degeneration. Although the causes of these diseases are different, they all end in the same way: with retinal cells dying through a process called apoptosis, which leads to blindness.

Dr. Tsilfidis and her team have shown that a gene called XIAP can block this process and prevent retinal cell death. The gene can be delivered to the eye using a virus called Adeno-Associated Virus (AAV). This therapy has proven particularly promising in an experimental model of retinitis pigmentosa, a genetic condition and important cause of blindness in which a large portion of the outer layer of the retina is lost. XIAP gene therapy was able to protect the cells of this critical part of the eye from dying, resulting in significant preservation of vision.

“Currently there is no therapy to prevent blindness from most retinal diseases, which is devastating news to more than one million Canadians losing their sight,” said Sharon Colle, President and CEO of the Foundation Fighting Blindness. “But the outlook for these families is changing to a more hopeful one thanks to groundbreaking research like this new project to save sight.”

“I've always hoped to hold out long enough to walk my daughter down the aisle, instead of having her lead me down the aisle,” said David Kong of Ottawa who has retinitis pigmentosa. “Maybe no one else would tell the difference, but it wouldn’t feel the same. That’s what I hope for.”

The new funding will allow Dr. Tsilfidis and her colleagues to further refine XIAP gene therapy and prepare for patient trials. Dr. Tsilfidis’ former mentor, Dr. Robert Korneluk, will be a crucial member of the team. Dr. Korneluk discovered XIAP at CHEO Research Institute in 1996 and he has helped to develop a cancer therapy based on XIAP that is currently in clinical trials. Other members include Dr. William Hauswirth (University of Florida), Dr. David Zacks (Kellogg Eye Center and the University of Michigan) and Drs. Stuart Coupland and Brian Leonard (both from the University of Ottawa Eye Institute at The Ottawa Hospital). Together, the team has extensive expertise in retinal surgery, retinal imaging and gene therapy clinical trials.

“Researchers in Ottawa have been particularly successful in working together to move discoveries from the lab into the clinic and this is another great example,” said Dr. Duncan Stewart, CEO and Scientific Director, OHRI, Vice-President of Research, The Ottawa Hospital and Professor of Medicine, University of Ottawa. “I’m delighted that Dr. Tsilfidis’ research will also benefit from some of the new facilities we are building through the $32M Translation of Innovation into Medical Excellence grant we received just over a year ago.”

The funding for this project through the Foundation Fighting Blindness is thanks to a generous donation from Scotiabank and a private donor.



About the Foundation Fighting Blindness
The Foundation Fighting Blindness (FFB) is Canada's largest private contributor of vision research, thanks to its generous donors and long-time annual fundraisers, Comic Vision and Ride for Sight. Since its inception in 1974, the FFB has funded dozens of research discoveries to identify the causes of genetic forms of blindness at universities and hospitals across Canada. Today, these discoveries have helped bring scientists to this very exciting time in vision research, translating knowledge into treatments to restore the gift of sight. To stay informed about progress in vision research, sign up for ‘e-news’ on our website: www.ffb.ca.


About the Ottawa Hospital Research Institute
The Ottawa Hospital Research Institute (OHRI) is the research arm of The Ottawa Hospital and is an affiliated institute of the University of Ottawa, closely associated with the University’s Faculties of Medicine and Health Sciences. The OHRI includes more than 1,500 scientists, clinical investigators, graduate students, postdoctoral fellows and staff conducting research to improve the understanding, prevention, diagnosis and treatment of human disease.
For more information, please visit: www.ohri.ca.


About the Canadian Institutes of Health Research
The Canadian Institutes of Health Research (CIHR) is the Government of Canada’s agency for health research. CIHR’s mission is to create new scientific knowledge and to enable its translation into improved health, more effective health services and products, and a strengthened Canadian health-care system. Composed of 13 Institutes, CIHR provides leadership and support to nearly 12,000 health researchers and trainees across Canada. For more information, please visit: www.cihr-irsc.gc.ca.


Please support vision research!

雪山飞狐

这篇文章讲的是加拿大和美国的研究人员现正开展一项为期5年，投资140万美元的合作项目，项目主要是一种新的基因疗法，好像是叫XIAP蛋白的蛋白的基因疗法，但是XIAP的的的意思是X性连锁视网膜色素变性的简称，不知道是什么意思。

我估计协和医院就是和他们在开展这个项目的合作！

黎明前的黑暗

如果到那时真的行了，可能我却已经不行了，快啊！一定要快！再不研究成功我就没救了！

心灵的窗

渥太华获得140万美元的研究人员领导的国际小组开发基因治疗视网膜失明
2010年3月8日
领先的视觉研究者从加拿大和美国现正开展一项为期5年，140万美元合作项目，制定新的基因治疗，防止失明，由于视网膜疾病。加拿大最大的视觉研究的私人慈善机构，基金会战斗盲目性，是合作与加拿大卫生研究所资助项目。研究小组包括凯瑟琳Tsilfidis博士，高级在渥太华医院研究所和香港大学医学院副教授渥太华大学科学家领导的6名科学家。

“这个项目的目标是在开始测试新的基因治疗病人，谁失去了5年后他们的视野，由于视网膜疾病，博士说：”Tsilfidis。 “这是一个雄心勃勃的目标，但我们认为这是可以实现的。我们迄今为止的结果令人非常鼓舞，我们的团队的奉献精神和经验带入诊所这个问题。“

视网膜是眼睛的内衬是用于探测光负责。在北美，数百万人患有疾病，涉及如视网膜色素变性，青光眼，视网膜缺血和年龄相关性黄斑变性的视网膜。虽然这些疾病的原因不同，但所有最终以相同的方式：与视网膜神经细胞死亡，通过这个过程称为细胞凋亡，从而导致失明。

Tsilfidis博士和她的团队已经表明，所谓的XIAP蛋白的基因能够阻止这一进程，并防止视网膜细胞死亡。该基因可交付使用眼病毒称为腺相关病毒（腺）。这种疗法已证明，尤其是在一个视网膜色素变性，遗传条件和盲目性，其中一对视网膜外层很大一部分原因是失去了重要的实验模型前景。 XIAP蛋白的基因疗法能够保护濒临死亡的这一眼睛的重要组成部分的细胞，在保护视力造成重大。

“目前根本就没有治疗，以防止最视网膜疾病，这是令人震惊的消息失明，甚至超过100万加拿大人失去视力，说：”沙龙叫柯里，主席和首席执行官基金会战斗失明。 “但对这些家庭的前景正在发生变化，以一个更加充满希望由于这样一个新项目，以保存视力的开创性研究。”

“我一直希望能坚持足够长的步行沿着过道，我的女儿而不是让她使我在过道，”戴维说，香港的渥太华谁有视网膜色素变性。 “也许没有人会发现其中的差别，但它不会同样的感觉。这就是我所期望的。“

新的拨款将允许Tsilfidis博士和她的同事进一步完善XIAP的基因治疗临床试验作好准备。博士Tsilfidis'前导师，博士罗伯特Korneluk，将是一个团队的重要成员。博士Korneluk发现了锈研究所于1996年XIAP的，他帮助制定一项癌症治疗的基础上XIAP的是，目前在临床试验中。其他成员包括威廉选段（佛罗里达大学），博士大卫扎克斯（凯洛格眼科中心和密歇根大学）和博士。斯图尔特科普兰德和Brian伦纳德（无论是在渥太华医院）从渥太华大学眼科研究所。一起，团队在视网膜手术，视网膜成像和基因治疗临床试验广泛的专业知识。

在渥太华的“研究人员一直在合作，特别是在离开该药物进入临床实验发现，这是一个很好的例子成功，”邓肯斯图尔特博士表示，首席执行官和科学部主任，奥赫里，副总统研究，渥太华医院医学教授，渥太华大学。 “我很高兴Tsilfidis博士的研究也将受益于我们正在通过创新的3200万美元将优质医疗翻译的建设给予我们只是在一年前收到的一些新设施。”

此战，通过盲基金会项目资金是由加拿大丰业银行的慷慨捐赠和私人捐助者表示感谢。



关于基金会战斗失明
该基金会战斗失明（FFB）是加拿大最大的视觉研究私人捐赠，其慷慨的捐助者和长期的年度筹款活动，为视力漫画视觉换乘感谢。自1974年成立以来，FFB资助了数十名研究发现，以确定遗传形式的失明大学和加拿大各地医院的原因。今天，这些发现将帮助科学家研究这个构想非常令人激动的时刻，知识转化为治疗恢复视力的礼物。留通报了视觉研究的进展，签署'了电子新闻'在我们的网站：www.ffb.ca.


关于渥太华医院研究所
渥太华医院研究所（奥赫里）是渥太华医院的研究机构，是对渥太华大学附属研究所，密切配合医药卫生科学大学的学院联系。该奥赫里包括超过1500名科学家，临床研究人员，研究生，博士后和工作人员进行研究，以提高认识，预防，诊断和治疗人类疾病。
欲了解更多信息，请访问：www.ohri.ca.


关于加拿大卫生研究所
在加拿大卫生研究所（卫生研究院）是加拿大健康研究机构，政府。卫生研究院的使命是创造新的科学知识，使将其译成改善健康，更有效的健康服务和产品，以及加强加拿大的卫生保健系统。 13个研究所组成，卫生研究院提供的领导和支持，近12,000名健康的研究人员和加拿大各地的学员。欲了解更多信息，请访问：www.cihr - irsc.gc.ca。


请支持视觉的研究！

心痛的妈妈

只研究X性连锁视网膜色素变性吗？别的基因不在其中吗？5年啊，真希望快点。

风之子

文章大意：
加拿大和美国的一流眼科专家正在进行一项为期5年的，预算为一百四十万美元的合作项目，用来研究新的防止由于视网膜病变导致失明的新基因疗法。此计划的目标是在5年内，对一种新的基因疗法进行临床试验。研究人员对此项试验很有信心。迄今为止试验的结果很好，研究人员希望尽快进入临床试验阶段。
研究人员发现一种叫做XIAP的基因（X连锁凋亡抑制蛋白）可以防止视网膜疾病恶化并防止视网膜细胞死亡。此种基因将通过腺相关病毒(AAV)输入到眼内。此疗法已证实在对视网膜色素变性的一例试验中（也许实验对象是动物，原文没说）非常有效。XIAP（X连锁凋亡抑制蛋白）可防止由于视网膜色素变性而导致的视网膜外层遭到损害，从而保住视力。

文中好像没有说针对哪种基因引起的RP

雪山飞狐

非常感谢风之子版主精确的翻译。

BOBOm

很感谢风之子版主的翻译，此疗法好像只谈到防止损害和保住视力，好像没谈到改善和恢复呀。

心痛的妈妈

是啊，真的很感谢风之子版主，能保现有的视力就已经很不错了啊。

雪山飞狐

下面一篇文章是渥太华眼科研究所一位科学家介绍这次研究的报道，好像也没有讲这个技术适合所以的RP患者。


The slow, patient path to discovery


By Tom Spears, The Ottawa CitizenMarch 11, 2010Be the first to post a comment
  
This woman knows something about long roads leading uphill. Cathy Tsilfidis climbed Mount Kilimanjaro four years ago, a celebration for surviving cancer, which was a long road of another kind.

The mountain wasn't what she expected. "A crazy idea," she says in retrospect, though with affection. The top was cold (about minus -5) with so much blowing snow that her group couldn't see the magnificent view from the highest point in Africa.

Back home in Ottawa, Tsilfidis is 10 years into another long journey. She's a scientist at the Ottawa Hospital Research Institute, and her team has just secured $1.4 million in funding that will pay for five years of work trying to prevent blindness from degenerative eye diseases.

The grant comes from the Foundation Fighting Blindness, a private charity, and the Canadian Institutes of Health Research.

In terms of curing disease, even a million and change is a drop in the bucket, paying for one more step on a journey.

"It's been almost 10 years now," Tsilfidis said this week.

She joined the University of Ottawa Eye Institute as a young scientist in 2000. With little previous experience with eyes. Her former supervisor had been looking for genes involved with how cells die, and found one. His work began in muscles, but it also raised the possibility that blocking the degeneration of muscles might also stop the degeneration of eyes.

The gene is called XIAP, pronounced Zye-app. In theory scientists can attach this gene to a virus that carries the gene into cells in the retina.

There are two tricks here: First, the XIAP gene has to become active and save the cell's life. As well, the surviving cells must also retain their ability to work as a retina.

But it's a long slog. Society has this funny idea that research means a guy in a white coat who stares through a microscope, decides that vitamin C cures cancer, and goes on to the next job. Works in the movies; takes longer in real life.

If the next five years pay off, the team should have enough evidence to justify applying for more funds to test the method in humans.

The lab has worked with rats prone to retinitis pigmentosa, a terrible degenerative disease that begins with the loss of night vision, then peripheral vision, ending up with complete blindness.

So far the gene therapy looks good: Treating one eye prolongs or even saves the vision of rats that are going blind, while the untreated eye continues to degenerate.

In the study to come, there will be six months of watching the rats. The rodents get a major eye exam every two weeks to see how the eye cells are reacting to gene therapy.

These eye exams required new equipment, and hundreds of people in Ottawa have had a hand in this without really realizing it.

If you attended a concert by the Blind Boys of Alabama in the spring of 2007, you helped raise about $45,000 to buy a machine that sends signals into the eye of a living person (or a rat), and tests whether the retina is functioning.

The machine is made for human patients, and one obstacle is to adapt it with lenses for animals with much smaller eyes.

Later, it gets trickier. They must analyse which cells have taken up the XIAP gene.

"We can see an area of protection (i.e. where eye cells didn't degenerate) but if we can't prove that our gene therapy was actually at that site, then we can't say that the gene therapy was what caused the protection," Cathy Tsilfidis says.

All this is what society gets for investing $1.4 million over five years. In fact, that's just part of the cost. All the researchers are on staff already, earning salaries from universities and hospitals. There are two eye surgeons, an electrophysiologist, a virus expert, a couple of eye disease researchers. Most are in Ottawa; two are at the Universities of Michigan and Florida.

Each has a lab with students, post-docs (recent PhD grads), and technicians.

Patients are already phoning Tsilfidis, asking for the new treatment. There isn't one, she must tell them, and this is hard news for people losing their eyesight.

She expresses confidence in the theory. "If I were going blind, I would absolutely have this therapy," she says. But there are no guarantees.

And it does take time -- 10 years to get this far, five more years beginning now, more years after that for trials in humans, assuming these are justified.

"I know how long it takes to achieve a goal. It's not like you do a project and it takes a week. You do a tiny bit of it and one week later it might give you an idea of what to do next. It is a long process."

Tom Spears is a member of the Citizen's editorial board.

E-mail tspears@thecitizen.canwest.com

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