Cerebellar Abiotrophy: Donating A Much-Loved Pet To Veterinary Science

[Boronia]

http://www.abc.net.a...-goldie/7790086

The trouble with Goldie

Donating a much-loved pet to veterinary science.

ABC South East SA By Kate Hill Updated about 10 hours ago

Once you fall in love with kelpies, Australia's loyal and intelligent working dogs, there is no going back.

Photo: A diagnosis of a rare and progressive brain disease would see kelpie pup Goldie put down and her remains donated to science. (ABC South-East SA: Kate Hill)

When I lost my Indie, my three-year-old rescue kelpie, to a car on a sunny Saturday morning in January this year, I knew it would not be long before another one would steal its way into my heart.

In the midst of a jumble of yapping bright-eyed puppies on a south-east farm, I met her.

She was chocolate-coloured, had a stumpy tail and was positively bursting with cheek and attitude, despite being the runt of the litter.

I took her home and called her Goldie.

The first sign that something was up with my young puppy was just a faint movement of the head, nearly imperceptible.

Those blue-grey eyes would fix on you, but her head would be nodding, nodding away all the time.

Watching Goldie play on the lawn in those first few weeks, it soon became clear there was something wildly off.

Her balance and walk were unsteady and every two or three steps she would crash blindly into the ground before hauling herself up to a wide-legged stance and launching merrily off again.

Photo: Goldie at eight weeks old: a stumpy tail and full of personality. (ABC South-East SA: Kate Hill)

She would fall down stairs and struggle to eat, her head refusing to stay in the bowl.

Sleep was the only time her little body would remain still.

Whatever she had, it did not seem painful. But there were times when I would look into those intelligent little eyes and fancy I could see some sort of awareness that all was not well.

And it was getting worse.

When her walk turned into a stagger and that once-adorable head nod developed into a violent jerking up-and-down, I booked a vet appointment.

A genetic lottery

Watching Goldie stumble around the floor of the clinic, my vet told me straight away she suspected she had early-onset cerebellar abiotrophy (CA), a rare brain disease passed onto puppies by a defective gene in their parents.

I had never even heard of it and my vet had seen just a handful of cases.

In itself, CA would not kill Goldie she said, but it would make her life hell. It would steal her balance, her movement and affect her ability to eat, drink, play and function as a normal dog.

It is a cruel kind of genetic lottery. The disease can sometimes pop up and swiftly affect numerous puppies in one litter, or creep up slowly on an animal when it is one or two years old and take years to progress.

CA variants have also been found in Arabian horses, Labrador retrievers and American Staffordshire terriers.

There is no treatment and no cure.

After symptoms grow progressively worse, many owners simply decide to end their dog's life.

I went home with Goldie and watched her play on the lawn. I could give a disabled dog a good life, couldn't I?

But an online search of the disease made me think again.

There were videos of staggering dogs wearing helmets to prevent them crashing into things and incredibly sad stories from owners who had to put down their adult dogs after the disease stole their agility and balance.

The words "heartbreaking" and "euthanasia" came up a lot.

Watching Goldie take a tumble down a small flight of stairs that night, I made the decision to put her down.

Late on a Thursday afternoon, the vet pressed the plunger of bright green liquid into her little veins and it took just a few seconds until Goldie's head shook for the last time, her body at peace in her favourite blanket.

There was one small bright spot in that afternoon.

The night before, I had been in contact with researchers at the University of Sydney, conducting a long-term study into cerebellar abiotrophy, hoping to develop a genetic test that might one day halt its progress in the kelpie breed.

Would I consider donating Goldie's brain and blood to the study?

The researchers were kind yet gently persistent, knowing that with her death, the window for her use in the study would close.

The need for something good to emerge out of this mess won out over my initial feelings.

As the vet took her little body away through a packed waiting room, I went home and began filling out pages of forms to give my consent for researchers to use her tissue samples.

With that, I passed Goldie over to the hands of researchers.

On the autopsy table

Later that night at the Mount Gambier veterinary clinic, Dr Rebel Skirving took a scalpel and carefully sliced open the skin over Goldie's head, then used a small bone saw to remove the top of her skull.

Delicately, she lifted the small brain out and placed it in preservative solution.

Replacing the top of her skull, Dr Skirving sewed the skin closed with small precise stitches of surgical suture.

"She just looks like she's sleeping," commented a vet nurse, who stopped to gaze at the young puppy on the table.

The whole procedure took just half an hour.

Photo: Goldie's remains ready to be picked up. (ABC South East SA: Kate Hill)

The nurse gently wrapped the body in a towel and then a muslin bag.

Sharing a shelf with tissue samples and blood transfusion packs, Goldie's remains spent the night in the clinic fridge.

The vet, who had seen numerous dogs affected by the disease over her years in practice, was keen to hear what the university's researchers have to say.

"I hope Goldie helps give us some answers," she said.

Search for an elusive gene

Tucked in ice in a small blue esky, Goldie's samples arrive by courier at the University of Sydney's Veterinary Faculty of Veterinary Science, one of Australia's oldest veterinary teaching hospitals.

The university houses the world's biggest collection of samples from CA-affected dogs.

On a mild Thursday afternoon, a red and tan kelpie wandered down the fifth floor corridor, wagging her tail.

Three-year-old Tangerine belongs to PhD student Annie Pan and, along with her beloved frisbee: she is a regular in the building.

Photo: A good place to bring your dog to work: Annie Pan and Tangerine, a regular at the faculty. (ABC South East SA: Kate Hill)

For six years Ms Pan, Professors Claire Wade and Rosanne Taylor and Associate Professor Peter Williamson, have been working to identify the rogue gene, or genes, responsible for causing cerebellar abiotrophy in the Australian working kelpie.

A genetic test to determine which dogs are carriers of the disease would let breeders know which dogs are affected. They could then retire them from the breeding gene pool, effectively eradicating CA from the entire population over a period of time.

It is a complex task, a kind of molecular detective work, which requires time, resources and ongoing funding.

Finding CA-affected dogs, before they are put down, is one of the study's main problems.

It is impossible to know how many affected puppies and dogs are simply put to sleep on the farm without ever seeing a vet or having an accurate diagnosis.

Goldie is one of only two dogs to be donated to the study so far this year.

Photo: Goldie's samples arrive at the lab. (ABC South East SA: Kate Hill)

In a busy fifth floor laboratory, test tubes filled with the blood of around 40 CA-affected kelpies from around Australia are banded together, identified by only a number and a name.

Participation in the study is strictly confidential. Finding out the disease runs in the bloodlines of their animals is upsetting for owners and breeders and can also affect the futures of valuable breeding animals.

Using a dog's blood to collect DNA, each individual chromosome will be scanned. A complex computer algorithm then interprets the information into endless reams of data.

Ms Pan will then study that data searching for a sequence difference in the genome of an affected kelpie, which will hopefully stand out when compared to healthy kelpies.

If the researchers are lucky, one difference will stand out above the crowd and pinpoint the problem region.

"Would you like to see Goldie's brain?" Ms Pan asks me, tapping a small white container.

Snapping on rubber gloves, she uses tweezers and deftly lifts the brain from its protective pool of formalin and places it gently on a small tray.

It is a strange thing to see — small and perfect-looking, with no outward sign of disease or abnormality.

Photo: Preparing to dissect Goldie's brain. (ABC South East SA: Kate Hill)

I find out about Purkinje cells or neurons, which form a layer in the cerebellum and play a critical role in brain function.

When CA ravages these cells, the affected animal loses its sense of space and motion, leading to the disease's distinctive range of symptoms.

After I leave, Ms Pan will get to work, dissecting the brain to see if CA is present.

When Goldie's results come back, they show that her brain is riddled with patches of degenerating cells, irregular spaces. Some Purkinje cells are missing altogether, a classic case of early-onset CA.

Five weeks after her death, the final box is ticked and she is now accepted into the study.

A genetic test for cerebellar abiotrophy may still be years of complex research away. (ABC South East SA: Kate Hill)

The researcher and her dog

When Ms Pan first began working on the disease seven years ago, she admits she knew nothing about the disease and had never heard of the Australian kelpie.

"After I started to get to know the breed, I realised the importance of a kelpie for people who are working on the farm," she said.

"If they have CA and can't work, farmers pretty much have no choice but to put the dogs down."

In some cases, owners have donated affected dogs and puppies for the researchers to observe, before they are euthanised.

Ms Pan confesses she often gets upset when clinically studying these animals, who become stumbling, nodding shells of the normally lightning-fast and loyal kelpie, once CA takes hold.

"It's just so sad," she said.

"It's not their fault but they just cannot enjoy their life like a normal dog can."

Somewhere along the line, the breed won Ms Pan over.

Three years ago, she picked up a tiny red puppy from a cattle farm in Grafton.

Now Tangerine plays her own part in the study, donating blood as a healthy control for Annie to compare to affected animals.

Photo: Annie Pan and Tangerine go for a run on the vast university grounds. (ABC South East SA: Kate Hill)

One day, Ms Pan hopes to find the mutation and play her part in eliminating the disease from the breed her life and study has become so entwined with.

"That would make me really happy," she said, while Tangerine sleeps at her feet.

"Knowing this would help save Tangerine's breed would make me really happy."

I leave the university happy, knowing that the study is in the hands of a fellow kelpie lover.

Moving on

Photo: Goldie and Indie's resting place, beneath the apple tree. (ABC South East SA: Kate Hill)

Goldie is buried in the backyard beneath my favourite apple tree. She's right next door to Indie, so they can keep an eye on each other.

Meanwhile, life moves on and that love of kelpies has won out again.

I've had Frankie for three months now and, although I watched him closely for signs of CA the first few months, he is just your average happy, healthy and semi-bonkers puppy.

Every so often, I'll get an email from researchers giving me the latest study updates.

The riddle of CA is not going to give up its answers easily and a genetic test for the breed may still be years away.

But in death, Goldie has played her part.

[sandgrubber]

Sad story. I feel for the people. I once donated a beautiful little Labbie pup to research. At three months, it was clear that this pup was going crippled and was going to need surgery on all four limbs to have a hope of leading a normal life. Both sire and dam had excellent hip/elbow scores. I hope somehow her little life contributed to a better understanding of the genetic causes of skeletal problems. Brings tears to my eyes to remember it. I think it was the right thing to do, but there's still deep sorrow.

Edited August 29, 2016 by sandgrubber

[Ruffles]

This is a very sad story, but a very noble cause.

There is hope. The speed at which they identified a marker, and created test for Cerebellar Ataxia (NCL-A) in Amstaffs was amazing.

Thank you for sharing!

[westiemum]

Well said Ruffles - sad story but a noble cause and a short life of value.

[OSoSwift]

I know of a Border Collie locally that was donated alive to Murdoch Uni as they wrre trying to develop a DNA test for CL in Border Collies.

It was highly suspected she had it but back then diagnosis was only definitive on PM and checking their brain.

She was a sweet little dog that taught so much and I like to think that her owners decision helped to create the test we have today so other people don't have to lose a dog like they did.

[Tassie]

I know of a Border Collie locally that was donated alive to Murdoch Uni as they wrre trying to develop a DNA test for CL in Border Collies.

It was highly suspected she had it but back then diagnosis was only definitive on PM and checking their brain.

She was a sweet little dog that taught so much and I like to think that her owners decision helped to create the test we have today so other people don't have to lose a dog like they did.

How generous and thoughtful of her people. Such a horrible problem .. and so thankful for the DNA test.

My BC girl is CEA affected (from the days when the only way to find out parental status was a test mating .. suspected carrier to a hopefully clear dog). I had her blood sent off to U Sydney when Dr Alan Wilton was calling for samples from affected dogs. I like to think that helped .. but that's an easy thing to do compared with what these owners have done.