Alzheimers Disease

21
Jul 2016
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Dr. Valerie Wallace (UHN Photo)

Cure for macular degeneration may be years away but scientist sees exciting advances on the horizon

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Dr. Valerie Wallace is realistic about finding cell-based cures for blindness.

“It’s a long road,” says the Dr. Wallace, Chair of the Vision Science Research Program at University Health Network’s Krembil Research Institute in Toronto.…

Dr. Valerie Wallace is realistic about finding cell-based cures for blindness.

“It’s a long road,” says the Dr. Wallace, Chair of the Vision Science Research Program at University Health Network’s Krembil Research Institute in Toronto. “Cell transplantation is tremendously complicated, difficult, and painstaking.”

But she is also optimistic about what the future holds for gaining a better understanding of the underlying causes of macular degeneration, which is triggered by deterioration of the cone photoreceptors (cones) in the centre of the eye that mediate reading and seeing fine detail. (In contrast, rod photoreceptors are concentrated along the edges of the retina to facilitate peripheral vision.)

“We are learning a lot about the biology that underpins photo cones, says Dr. Wallace. “They are a rare cell type and understanding their development has been difficult. Now we have tools to do that. That’s what I’m excited about.”

Her lab has developed a new mouse strain with fluorescently tagged cones to allow the researchers to track the progress of the cells to see if they can rescue visual function when transplanted into blind mice.

“We’re looking directly at this. Can cone cells transplant? Can they rescue vision? And if they can, what stage of cone development is the best for transplantation?”

The work she is doing feeds into a larger team effort dedicated to optimizing how to make photo receptors from human stem cells. What she learns from trying to engraft mouse cells will be applied to people. It also has implications for finding therapies for other neural degenerative diseases, such as Parkinson’s disease, Alzheimer’s and stroke.

“The eye has always been thought of as very different from the brain,” she says, “but it is part of the brain.  Our work on identifying novel approaches to promote the survival of these cells could extend to  promote neuron survival in other parts of the central nervous system.”

And the eye, aside from being the window to the soul, can also be a window into a person’s health. Says Dr. Wallace: “People are now using non-invasive imaging of the eye to look at markers of disease. There is a large study in Alzheimer’s that is imaging the eye to identify people at early stages of the disease. That’s happening more and more. People are appreciating that some aspects of eye health might inform the progression or even the diagnosis of other diseases.”

Dr. Wallace, who calls herself “a developmental biologist at heart,” doesn’t forget who she’s working for: people struggling with vision loss. Her past work with the Foundation Fighting Blindness, which helps fund her research, guarantees that. “I hear a lot about what’s important to patients.”

While progress is taking time, the science is steadily moving forward. “A lot of the things we’re doing now were not even being talked about 10 years ago.”

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06
Jan 2016
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A model approach to treating disease

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When most of us think about using stem cells to cure disease, we picture these building block cells being injected into damaged tissues or organs to help repair and rebuild them.…

When most of us think about using stem cells to cure disease, we picture these building block cells being injected into damaged tissues or organs to help repair and rebuild them.

According to a recent Wall Street Journal article, there are more than 300 clinical trials underway around the world to test stem cells’ ability to treat diseases such as heart attack (read about a Canadian study here), stroke and amyotrophic lateral sclerosis — among others. The general idea is to get the stem cells to where the disease is doing damage so they can affect healing.

But, as the WSJ article points out, there is another approach in which stem cells are used to create models of disease outside the human body, in a Petri dish. These models not only provide researchers with a closer look at the molecular makeup of a disease, they offer the opportunity to test drugs that might be effective against it. The article highlights research at the University of California, San Diego where stem cells are being used to make Alzheimer’s neurons to test the safety and effectiveness of potential drug therapies.

There are real benefits to this approach. For one, it’s a supplement to using animals as disease models. Sometimes animals aren’t susceptible to the same diseases as people. In Alzheimer’s, for example, researchers use mice that have been altered to carry different genes or combinations of genes associated with the dementia.

The stem cell model approach also can save time and money. If scientists can rule out a compound as ineffective before moving to clinical trials, it can prevent years of work being done and millions of dollars being spent to travel down a research road that ultimately is a dead end.

Also, advances in technology mean scientists can use high-throughput screening to test hundreds, even thousands, of compounds against model tissue or organs to find a good candidate to shut down the disease — the research equivalent to finding a therapeutic needle in a haystack.

 

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03
Dec 2015
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Dr. Eva Feldman

Major trial for ALS therapy in the works

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Dr. Eva Feldman devoted 12 years to working on a drug-based cure for amyotrophic lateral sclerosis (ALS).  It was, she says, “a very big endeavour.”  It failed.…

Dr. Eva Feldman devoted 12 years to working on a drug-based cure for amyotrophic lateral sclerosis (ALS).  It was, she says, “a very big endeavour.”  It failed.

So, in 2006 the University of Michigan clinician/researcher took a sabbatical to rethink her approach to fighting ALS, the cruel, fatal condition that attacks the nerve cells (neurons) that control muscle movement.  “I wanted a break,” she says.  In California, Dr. Feldman found scientists doing interesting animal studies on treating spinal cord injury with stem cells. It changed her perspective entirely.

Today, with two early-stage human studies behind her, Dr. Feldman hopes to soon begin a large-scale clinical trial to test whether human neural stem cells injected into the spinal columns of ALS patients can stop the disease from stealing their ability to walk, talk, eat and breathe.

“We inject the cells into the high part of the spinal cord of patients with ALS with the goal of protecting the large motor neurons that are necessary to maintain normal breathing.  Our goal is for the stem cells to go into that area, surround the neurons that are starting to get ill and nurse them back to health.  We do very similar injections in the lumbar area of the spine to preserve the neurons that go to the muscles that allow patients to walk.”

Preclinical studies she and her team conducted on rats and pigs showed that the stem cells “take a really bad environment and clean it up.” Inflammation is ameliorated and the stem cells surround the large, ailing motor neurons and nurse them back to health. “The cells go from looking like they are about to die to being quite healthy and robust,” says Dr. Feldman.

Phase I and II clinical trials involving 30 patients went “extremely well,” she says, with the procedure proven to be safe and the patients able to tolerate the accompanying immuno-suppressant therapy. “We have good preliminary data,” she says.

Neuralstem Inc., Dr. Feldman’s industry partner in the project, is organizing a large, multi-centre trial in 2016 to test whether the procedure truly works. Richard Garr, the company’s Chief Executive Office, is understandably guarded about the details, saying via email that his company is working with the U.S. Food and Drug Administration and that “all of the issues with respect to the scope and nature of the trial are still being determined.”

Dr. Feldman, who has been down this road before with the failed ALS drug, is cautiously optimistic.  “As enthusiastic as I am about the therapy, until we do a very large trial we simply won’t know with certainty that this is the hopeful home run that we want it to be.”

For Ted Harada, a 43-year-old former FedEx manager in Atlanta, Dr. Feldman’s stem cell therapy has been a life-saver. The recipient of two stem cell implant surgeries, he has seen his decline from ALS virtually stopped.  The normal survival period for ALS, which is sometimes called Lou Gehrig’s disease after the New York Yankee slugger who succumbed to it, is about 36 months. He is now five years out and feeling good, although he still has the disease.

“I put my cane down two or three weeks after the (second) surgery and I haven’t picked it back up,” he says.  “When I had my fifth year anniversary, my doctor said ‘Ted, I would have guaranteed you’d be dead within two or three years when I first met you.’  I like to say that the surgeries set the clock back to what I call onset.”

Dr. Feldman says other patients in the studies also have done well but “the numbers are small … until our numbers are larger we can’t say with certainty.”

While criteria haven’t been set, participants in the larger trial likely will need to be in the early stages of the disease, with the ability to breathe reasonably well and speak and swallow without difficulty. Dr. Feldman says Canadian patients might be eligible if they can travel to a surgical site — but, again, details are still being worked out.

Dr. Feldman is also excited about the possibility of using the same kinds of stem cells to treat the dementia disease.

“I have beautiful preclinical data in animal models of Alzheimer’s. We’ve shown that the injection of stem cells into the selected areas of the brain that are required to form new memories rescues the animals and they are able to function normally. We see the accumulation of amyloid, which is the build-up of plaque that patients get, gone. The stem cells go in and they are just like garbage disposals, cleaning up all the garbage.  It’s remarkable.”

 

 

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02
Sep 2015
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Dr Karl Fernandeds (CBC News)

Canadian researchers make headway against Alzheimer’s, liver disease

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It has been a very good week for Canadian stem cell researchers, with two significant discoveries.

(Both discoveries show how Canadian scientists rank among the best in the world in the field of stem cells and regenerative medicine.

It has been a very good week for Canadian stem cell researchers, with two significant discoveries.

(Both discoveries show how Canadian scientists rank among the best in the world in the field of stem cells and regenerative medicine. Our Foundation advocates for the Canadian Stem Cell Strategy & Action Plan to accelerate the translation of research discoveries into new, safe and effective treatments for a number of diseases. During the election campaign, we’re urging all Canadians to help put stem cells on the government’s agenda.  It only takes two minutes.  Just click here.)

First came news last Thursday that researchers affiliated with the University of Montreal Hospital Research Centre have identified fat droplets in the brains of patients who died from Alzheimer’s disease. These deposits appear to block stem cells from repairing brain tissue, possibly triggering dementia.

The fat deposits have been hiding in plain sight for more than 100 years. “We realized that Dr. Alois Alzheimer himself had noted the presence of lipid accumulations in patients’ brains after their death when he first described the disease in 1906,” says Laura Hamilton, a doctoral student who found fat droplets near the stem cells in the brains of mice predisposed to develop the disease. “But this observation was dismissed and largely forgotten.” Her remarks are highlighted in the research centre’s press release about the discovery.

The findings have implications for treating and potentially curing dementia, which currently affects almost 750,000 people in Canada, according to the Alzheimer Society of Canada’s Mimi Lowli-Young, who was featured in a CBC News report on the discovery. The Alzheimer Society helped fund the work.

The hope is that drugs to block fatty acid build-up, which are now being tested to fight obesity, could also help treat dementia. “We succeeded in preventing these fatty acids from building up in the brains of mice,” explained the University of Montreal’s Dr. Karl Fernandes. “The impact of this treatment on all the aspects of the disease is not yet known, but it significantly increased stem cell activity,”

Finding a treatment is still years away. But the discovery opens a new pathway to combat Alzheimer’s.

The second Canadian accomplishment comes from the lab Dr. Gordon Keller, Director of the McEwen Centre for Regenerative Medicine in Toronto.

A team of clinicians-scientists has found a way to generate 3D bile duct structures from human stem cells. The structures will allow scientists to study bile duct disorders, which cause liver disease, and test new treatments.

“Until now, we have not had a good scientific model to study the human liver’s bile duct system,” explains Dr. Anand Ghanekar, a clinician-scientist at Toronto General Research Institute, in a University Health Network news release. “We need to be able to study a patient’s disease in a dish at the basic cellular and molecular level. Stem cell technology gives us a totally different way of evaluating and then treating these defective cells.”

The discovery also has implications for treating Cystic Fibrosis because many patients with that disease also have defective bile duct function and liver disease.

 

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23
Jul 2014
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Nature Screen Capture

Hope, time and (good) practice

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An editorial in the June 11th edition of Nature does two things remarkably well: it offers hope for the future of stem cell science while explaining why it takes so long to get things right.…

An editorial in the June 11th edition of Nature does two things remarkably well: it offers hope for the future of stem cell science while explaining why it takes so long to get things right.

Headlined “Good practice” the Nature piece explains why: “… shortcuts are simply not possible, despite charlatan claims. It takes time to learn how to coax stem cells — either from human embryos or from reprogrammed adult cells known as induced pluripotent stem (iPS) cells — to develop into the right sort of replacement cell. It also takes time to work out how to get these cells to integrate into the host tissue and to function. And the steps required to work out how many replacement cells need to be delivered, and how to deliver them safely, cannot be rushed …”

The editorial urges patience as the field “inches towards clinical testing” and points to two recent developments that inspire considerable optimism.

One is the commencement of clinical trials to treat macular degeneration using retinal stem cells (covered in previous posts here).

The other is the resumption of a clinical trial to test whether embryonic stem cells can help regrow nerves damaged by spinal cord injury. The original trial was halted in 2011 when Geron, the company behind it, decided to use its limited resources elsewhere. Now Asterias Biotherapeutics, buoyed by a $14.3-million grant from the California Institute for Regenerative Medicine, is picking up where Geron left off. (Nature doesn’t mention a Canadian led spinal cord study, but you can read about it here.)

As the article points out, the eye and the spine, in terms of stem cell research, present somewhat easier paths to the clinic: both are isolated, closed systems. The brain and heart, however, are far more complicated. Developing new, stem cell-derived treatments for diseases like Alzheimer’s and Parkinson’s and for cardiovascular conditions will be far more complicated. But there is reason for hope: “Happily, clinical trials are on the horizon. Treatments for Parkinson’s disease are just a few years away from clinical testing. And some for Huntington’s disease may not be far behind.”

One of the reasons things have taken so long is the relative newness of the field: the discovery of embryonic stem cells, which triggered much of the explosion of research underway today, was just 16 years ago. Getting scientists to agree on standardized processes and protocols has taken time. The editorial points to early-days clinical trials for Parkinson’s that didn’t use standardized practices, leading to varying results that were an “uninterpretable mishmash.”

The editorial praises Parkinson’s Disease Global Force, which is bringing together research teams from Europe, the United States and Japan to define standards for cell preparation and patient selection and monitoring for future trials. The scientists will share their universally applicable results, which in turn will move the science forward toward finding treatments and cures.

In short, there will be more trials, fewer errors. And, in the not-too-distant future, new treatments.

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