Dementia researchers look to dogs for breakthroughs
Like more than 342,800 Australians, Timmy the cocker spaniel is living with a form of dementia. Three months ago, he became part of a University of Sydney research project focused on rebooting the brain with stem cells harvested from the subject’s own skin, and in doing so became the first dog worldwide to survive such a transplant. Now Timmy faces a series of ongoing tests designed to measure improvements in his canine condition, which is similar to Alzheimer’s disease, the most common form of human senility.
Associate professor Michael Valenzuela, who heads the university’s regenerative neuroscience group, was cautiously optimistic this week in his first set of interviews since the August transplant.
“Our latest results are promising,” says Valenzuela, referring to measurable improvement in Timmy’s dementia-like behaviour that includes senseless barking, staring into space and constant nightly sleep disturbances.
Valenzuela has been working on a cure for dementia for more than a decade, investigating whether missing neurons and their interconnections (synapses) can be replaced using a form of stem cell therapy.
“There is international interest now in the prevention of dementia – that is probably the fastest-growing area of research,” he says. “But if we ever want to find a cure, we are going to need to repair and regenerate those millions of lost brain cells that are the hallmark of dementia.
“This is why our trial is so exciting, because we have been able to do that in rats and now we are trying to do the same in our canine patients.”
In collaboration with neurosurgeon Erica Jacobson and the Faculty of Veterinary Science, Valenzuela moved on to the Dogs+Cells Trial in 2013.
The aim was to investigate whether the dementia-like syndrome canine cognitive dysfunction (CCD) can be reversed by injecting a dog with its own stem cells directly into the hippocampus using MRI guidance. The hippocampus is thought to be the brain’s centre of emotion, memory and the autonomic nervous system.
But finding suitable dogs in the community with CCD has been challenging. As well as adhering to the university’s strict ethical code, the team also had to find owners willing to allow often treasured pets to undergo two bouts of general anaesthetic and cell transplantation into the brain.
Only one other dog has reached the transplant stage, but he did not survive due to complications associated with a pre-existing kidney condition.
“Owners are naturally protective of their animals,” says team vet Sarah Toole, who helps find suitable research candidates.
“The biggest hurdle has been their concern over an old dog’s ability to deal with anaesthetic, but with improvements in modern anaesthetic the alternative [CCD] holds far more risk to an animal’s wellbeing.’’
Toole diagnosed 13-year-old Timmy with CCD in January this year.
Timmy belongs to a Wollongong couple, Tony and Michele Leeder-Smith, who adopted him at 10 months when several other families were unable to cope with his congenital deafness.
“He chose us really. He walked through the door and made it pretty clear he didn’t plan on leaving,” says Michele.
His disability, however, did not make him any less of a normal, naughty, shoe-chewing puppy who loved cuddles and attention.
“It was funny to watch him nudge books out of Michele’s hand when she’d sit down for a quiet read,” recalls Tony.
Timmy from the outset chose his mark to help him cope with his disability in the outside world.
“We had a golden retriever named Kate when Timmy joined us,” says Michele. “He stuck to her like glue on walks because she made him feel safe and protected.’’
But the loving, tranquil dog Timmy grew into started to disappear about a year ago when the shadows on the wall he used to delight in chasing held no more fascination.
“He started getting up in the middle of the night and would sit in the kitchen where he would stare and bark at nothing,” says Tony.
As Timmy’s condition worsened it got to the point where he could no longer work out how to climb on to the bed or use the dog door.
The couple took their ageing pet to his vet, who then referred him to Toole. She came back with the CCD diagnosis after using a rating scale developed at the University of Sydney.
Toole first trialled Timmy on available medication but when that provided only temporary relief, the Leeder-Smiths were invited to join Valenzuela’s trial.
The couple agree it was not an easy choice.
“Timmy is an important part of our family because we don’t have children together,” says Michele. “Tony and I had to think long and hard about the risks involved and if it was fair on Timmy at this stage of life. But we were at a point where his broken sleeps and barking became intolerable, especially for Tony, who bore the brunt.”
Eventually they decided that without intervention Timmy would progress to the point where there was no quality of life for him or anybody else in the house.
“We were also mindful of the big picture and how many people this research might eventually help,” says Tony.
With the family’s green light, the Sydney Uni team grew the stem cells created from the skin of Timmy’s belly and, at optimum size, transplanted them into his brain about a fortnight later.
The surgery went smoothly with the nine-person team on tenterhooks for the next 24 hours. Toole spent a long night beside Timmy to ensure he remained calm and comforted if he awoke. The cocker spaniel began to bounce back from the surgery within a few days.
The first of a series of memory tests was performed on Timmy this week in a sand maze, where he was tasked with locating buried treats by memory rather than smell.
The results are still to be analysed but because of Timmy’s near blindness due to his age, the team is unlikely to put great significance on that particular test.
The documented behavioural improvements supplied by the Leeder-Smiths are considered more significant. Their observations have been supported by data collected through a collar provided by the researchers that monitors sleep and activity patterns that can be compared with baseline pre-transplant data.
That data since the transplant (collated in graph form) is now showing significantly reduced sleep disturbance, a symptom associated with dementia in both animals and humans.
“This was one of the behaviours that most troubled Tony and Michele before the transplant,” says Dr Toole, who has been in close contact with the couple since January.
Overall, they are pleased with Timmy’s progress.
“At first we were just relieved he survived the surgery, but now everybody is pretty impressed with how well he is going,” says Tony.
“We are in no position to say if Timmy’s improvements are directly linked with the stem cell transplant, but we do know for sure our lives are now more bearable than they were 12 months ago.
“We realise we can’t change the fact Timmy is still physically an old man, but what’s really important to us is that we’ve regained some of the connection with the loving little mate we lost along the way.”
The team hopes to involve more dogs in the research and Valenzuela says if it is successful, the next step will be a human trial.
This article was first published in the print edition of The Saturday Paper on Nov 21, 2015 as "Talkin’ bout regeneration". Subscribe here.