The game changer

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MICHAEL-VALENZUELA-0026_PPImagine a technique that could one day reverse the memory loss associated with dementia. An Australian researcher is now trialling a world-first stem cell therapy in dogs that aims to be a game changer, and it could lead to new treatments for Alzheimer’s in humans, writes Fiona MacDonald.

Just like humans, dogs’ mental sharpness can decline as they get older. With many pets now living well past a decade, it’s not unusual for previously clever canines to suddenly start staring at walls, getting lost in their own garden, or pacing the house for hours. Some dogs may even forget their owners. Vets have long been aware that this happens—after all, dogs are our best friends—but up until around 10 years ago this type of behaviour was assigned to old age, and distressed owners usually ended up putting their pet down in order to end their suffering.

Associate Professor Michael Valenzuela, head of the Regenerative Neuroscience Group at the University of Sydney, has spent the past eight years studying the condition—now officially known as canine cognitive dysfunction [CCD]—and has come up with a 13-question online test to help diagnose it. In fact, his research suggests that 12 per cent of dogs over the age of eight are suffering from CCD. “People think it’s just a normal part of ageing and getting old, but that’s completely wrong,” he explains. “This is a separate medical condition with its own pathology and its own long-term trajectory, and vets are only just beginning to realise that.”

Interestingly, he’s also found that CCD in dogs is remarkably similar to Alzheimer’s in humans. Not only do dogs share the same behavioural symptoms as they get older, such as memory loss and disorientation, but the condition seems to be the same on the biological level too, which means that studying dementia in dogs could teach us a lot more about what’s going on in our own brains. In both humans and dogs, dementia is triggered when toxic proteins known as amyloid plaques begin to build up in the brain. This build-up is associated with the death of brain cells and it begins in the hippocampus—the brain’s memory centre—which is why memory is the first thing to go. From there, the damage gradually spreads to interfere with communication and bodily functions.

Unfortunately, just like in humans, there’s also no reliable way to treat CCD in dogs. Several Alzheimer’s drugs are currently being prescribed by vets, but they can have severe side effects and, best case scenario, all they can do is halt the progression of the dementia—and by the time it’s been diagnosed, the condition is usually so bad that the dog is already suffering.

However, Professor Valenzuela and his team are trialling a new way to not just treat dementia, but actually reverse the condition, and help to restore dogs’ memories—and the results could have big impacts for humans, too. The group’s aim is to use stem cells to heal damaged brain tissue in dogs with CCD, and re-grow the missing neural connections. “What we’re trying to do is reverse or significantly improve dogs’ clinical condition, so reverse their dementia state through transplantation of stem cells into the brains of these dogs,” says Professor Valenzuela.

Known as the DOGS+CELLS Trial, the technique involves two stages. First, Professor Valenzuela takes a little piece of skin from a dog’s abdomen and uses that tissue to grow more than a million brain stem cells in the lab. These stem cells are able to transform into any cell type that the body requires. A few weeks later the stem cells are then injected back into the dog’s hippocampus, where they’ll hopefully start to patch up any damage caused by the amyloid plaques.

Because these cells are unique to that animal, they’re less likely to be rejected by the body. “It’s a kind of tailored therapy,” explains Professor Valenzuela. “We’re using a dog’s own cells to treat the condition in their brain.”

Scientists are already trialling similar tailored stem cell therapies in humans to treat conditions such as multiple sclerosis and age-related blindness. But it’s only recently that researchers have started to realise that the stem cells may also be able to heal the brain. “We used to think that we didn’t have the capacity to grow new brain connections and that the brain cells we had when we were born were the ones we’d have until we died,” he says. “But we now know that’s not true. If we can stimulate stem cells in the brain they can replace damaged tissue.”

His team has already shown that their technique works in rats. In earlier trials, they injected stem cells into the brains of old rats and were able to restore their memory function to a younger state. “After the therapy, they could remember the location of different objects in their pen—an ability that usually disappears after the age of one in rats,” explains Professor Valenzuela. Analysing the brains of these rats showed that the stem cells had started making new connections in the hippocampus, just like they’d hoped. They’re now trying to see if the same thing will happen in dogs.

Ironically, Professor Valenzuela never intended to work with animals. His main interest is in the brain’s ability to heal itself using stem cells. But until eight years ago, his research was limited to work on humans. It wasn’t until he took his dog in for a check-up and started chatting to his vet about his job almost a decade ago that he heard about doggy dementia. “I’d never heard about it before,” says Professor Valenzuela. “He explained some of the symptoms to me and it sounded a lot like Alzheimer’s in humans. But there was no formal way to diagnose it as yet, and so I decided to investigate. “

He’s since made great strides in improving the detection of the disease, but what’s most exciting for him is how similar CCD is to human Alzheimer’s. That’s a big deal, because currently all of our Alzheimer’s research is based on rodent models—but mice and rats don’t naturally get a build-up of amyloid plaque in their brains, so the research doesn’t translate so well to humans. “There are lots of similarities between dog dementia and human dementia. On the surface there’s memory loss and disorientation,” explains Professor Valenzuela. “On a deeper level the same amyloid plaque builds up in dog brains as human brains. That’s a big difference between rodents and dogs, and it means there’s a lot of value in studying the dog model.”

On top of the biological similarities, dogs also live alongside humans and share a very similar lifestyle. “What all of this means is that if this stem cell trial reverses dementia in dogs, we can say with a lot of confidence that it will also work in humans,” says Professor Valenzuela. In fact, if the DOGS+CELLS trial is a success, he predicts that the technique will very quickly move to human trials.

Right now, we’re still a few years off knowing whether or not that’s the case, but two dogs have already received the stem cell therapy, with varying outcomes. The first dog in the trial unfortunately had to be euthanised as a result of a complication from the surgery. Professor Valenzuela insists this wasn’t to do with the stem cell treatment, and was simply a result of the invasive techniques used on the older dog. “We did a really in-depth analysis of that adverse outcome and we re-did our protocol. We now feel confident that we have a safer and better procedure,” he explains. “It was emotionally tough, even though we knew logically it could happen.”

Fortunately, the second dog to be treated, a 13-year-old cocker spaniel, was up and about within a few hours of surgery. Five weeks on, it’s still doing well, with the official check-ups scheduled three and six months after the treatment. “We’ve had encouraging reports from the owners but they’re anecdotes. We don’t really know until we’ve done our proper tests,” Professor Valenzuela explains.

“It’s hard to get too excited because there are no guarantees, and you can’t trust one experience or one experiment. We’ll probably need to wait for around 10 animals to be treated before we can say with statistical confidence that this has worked or it hasn’t.”

They already have one new owner interested in taking part in the trial and are now looking for six or seven more—the dogs need to be over the age of eight, suffering from the symptoms of CCD, physically healthy, and living in Sydney. And if their trial works? “It would be one of those red-letter days in medicine and veterinary medicine,” says Professor Valenzuela. “We would have evidence for the first time that we can do something about dementia, and that it would probably work for humans. That would be huge”

The success would also change the way that dogs are treated, and help them to live with us healthier for longer. “If we could manage to find a technique that helps treat dementia in dogs then it would have a huge impact on them and their owners,” says Professor Valenzuela. “Over evolution, humans and dogs have created a really special relationship and so I think there’s a lot of possibilities,” he adds. “I think neuroscience could do well to look to dogs more and more for inspiration on how to understand the human brain because a lot of their behaviour has human parallels.”

If you know of any dogs or owners who may want to get involved with the DOGS+CELLS Trial, contact Sarah O’Toole on 0418 838 911.

You can test your dog for CCD at: http://www.surveygizmo.com/s3/1839821/Canine-Cognitive-Dysfunction-Rating-scale-CCDR

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