加拿大渥太华医院研究所开始新的基因治疗研究

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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.


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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！

雪山飞狐

非常感谢风之子版主精确的翻译。

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

© Copyright (c) The Ottawa Citizen

雪山飞狐

11# 罗兰德尼奥 [

不知道罗兰讲的是哪一种多基因遗传，是一个人身上有两个基因或两个以上的基因遗传，还是RP致病基因有50多种的基因突变的遗传的多基因。