Dr. Nick Jeffery: How pet dogs can help us understand the value of new therapies for spinal cord injury

Causes of human SCI in the USA

  • car crashes -37%
  • violence- 28%
  • falls- 21%
  • sports-related-6%
  • other – 8%
  • Of course, what we all want is to reverse the effects of the injury and restore ourselves back to where we were.

How do we do that? Traditionally, with lab rats. Why use rats? because you can’t test therapies directly in people, and in animal models you can pretty much make all the injuries exactly the same. And that makes it easier to figure out if some intervention worked.

This is great BUT with artificial injuries, you’re missing a lot of factors that vary the outcome in human injuries, which are radically different.

The question is always, will this therapy be effective in a person? You can look at statistical differences to guess what might be meaningful, but you’re always guessing.

So, that’s where working with pet dogs can help. SCI is very common in dogs, especially in certain breeds. Also dogs are a lot bigger than rats, which makes it simpler to guess whether or not a treatment will scale up, so to speak. What works in a tiny rat cord hardly ever works in a person.

But the best thing is that the disease process is similar — it’s a real life injury. And scientists have access to both acute and chronic patients. There’s a lot of variation in age, weight, lesion nature, severity, and genetics — just like in humans.

So, how do dogs with sci show up at the vet? In the acute phase, just like us — their back legs don’t work. In the chronic phase, they use these little “chairs” attached around their middle with wheels to help them get around. (It looks uncomfortable in exactly the same way a wheelchair does . . . )

(Image of a fracture in the spine of a coon hound that was chasing a coon up a tree and fell) They use MRI to diagnose dog SCI just like they do with humans.

ACK. Showing video of them testing sensory function with a pair of pliers applied to the tail and the feet . . . he’s saying that it’s the very best way to figure out the prognosis very soon after injury. There’s a scale for dog injuries that’s analogous to the one we use (ASIA); it’s called TL. The first four categories have about a 95% recovery rate. The fifth has less than 5% recovery after 3 months.

You see where this is going, right?

They did a trial on that fifth group — the “hopeless” dogs. They looked at particular lesions in the thoracolumbar region, and they chose to work with small dogs, mostly because it’s too hard for people to take care of big paralyzed dogs.

They randomized the dogs into two groups — one that got the treatment and one that served as a control . . . the controls got a sham injection; the treatment dogs got a real one. The people who worked with the dogs after that didn’t know which was which.

Showing video of a para dog on a treadmill, which can’t move its feet unless you hold its tail up high and pinch it . . . the dogs hind legs then move right along in a stepping pattern.

Image of a dog with digital markers on its limbs that can be captured with infrared light and used to measure movement & coordination in really precise ways. They also measure electrophysiological outcomes (signal getting to muscle through the injury), and urodynamics with plain old catheters.

They’ve already published one study, which used autologous olfactory mucosal cell transplants (OECs) . . . you can find it in Brain here.

One of the cases was a 7 yr old male dachsund with a compression injury. (His name is Henry.) Henry didn’t recovery spontaneously . . . he got the OEC injection after being randomized to the treatment group. There were 34 dogs in this study, and Henry was one of 23 who got the cells.

They followed the dogs for six months afterwards . . . and saw gradual improvement. At six months the video shows him walking (with difficulty) along the treadmill. This was good, but it was “cumbersome” to get the cells out of the dogs’ noses, culture them for several weeks, and then inject them. They wanted to try something better & simpler.

Image of the glial scar, full of CSPGs that inhibit axon growth. We know that ChABC (chondroitinase) tends to eat up CSPGs. They’re using a form of ChABC that’s heat-stabilized so that it k

They’ve so far recruited 42 cases and are aiming for 60 by the end of the trial, probably about a year from now. There’s a PT component that involves swimming . .. can’t give us results until they’re finished, GAH — I really wanted to hear at least a hint!

Credit for funding to Spinal Research of the UK. You can follow them on their facebook page. 🙂

Q: about that dog who could walk with his tail pinched and held up high. how did that work?

A: the lesion would have been around t-13 . . . the part that deals with back leg reflexes is below that. the reason is supposed to be plasticity in the remaining healthy bit of the cord . . it reverts back to some neo-natal reflexes–stepping movements not controlled by the brain.

Q: are all the dogs in the ChABC trial motor and sensory complete, and do they get PT before?

A: yes, they’re all motor/sensory complete. they’re also a long way out from injury, so many of them have had other things tried . . . we do require that their joints are still functional

Q: are the OECs terminally differentiated? or are they precursors (stem cells)?

A: yes, they are. they’re not stem cells. the biggest problem we have is that the source of them contains other types of cells, so we have to sort them very precisely, which is challenging . . . and while there was improvement, it wasn’t life-changing enough to justify the procedure

Q: if chABC was shown to be effective by your studies, would it come on the market for dogs, i.e., without all the protocol required for human trials?

A: ah, my knowledge of the US protocol isn’t complete enough to answer that question . . . (he’s British) . . .

Q: any anecdotal or owner stories about the controls getting better?

A: at the end of the trial we ask the owners, and at least 90% say their dogs got better. BUT the lab tech could guess with much better accuracy.

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