Here’s a cringe-worthy mash-up from actual headlines for the story of Jasper, a paraplegic U.K dachshund who regained hind limb function after getting spinal injections of cells from his nose:
Walking the Dog:
Revolutionary Groundbreaking Miracle Stem Cell Cure Offers Hope.
Indeed, this one got full blast adjectivization – it is compelling enough to see treatment and recovery in the same story but the real clincher was the irresistible footage of little Jasper before and after his miracle revolutionary cure. If you missed it, start here, from the
Daily Telegram in London. This includes the video of Jasper, at first dragging his hind legs suspended by a harness, and then, after he got injections of cells harvested from his nose, scooting along almost normally, wagging his tail. Said May Hay, Jasper’s owner: “It’s utterly magic.”
Seriously, this is a very cool experiment and important to move the cell therapy field along – but not so much, headlines notwithstanding, to move it right over to human trials. The bottom line, not from news media but from the publshed research: This treatment is limited. "...it is improbable that patients would experience useful benefit in their everyday lives."
Here is the full article in the journal
Brain: “
Autologous Olfactory Mucosal Cell Transplants in Clinical Spinal Cord Injury: a Randomized Double-blinded Trial in a Canine Translational Model” (you can read the whole paper, not just an abstract --click on “full text.”) The University of Cambridge, where most the work was done, offered a
statement.
Jasper was one of 35 dogs paralyzed three months to year ahead of being randomized to get either nose cells or placebo; 23 got cell transplants and 11 got cell transport medium only. The researchers doing the surgeries were blinded; they didn’t know which dog got what.
Jasper was among the lucky dogs that got a brew of cells harvested and cultivated over a period of weeks from the olfactory mucosa of their noses. These cells are called olfactory ensheathing cells. They are not new to the neuroscience world: Almundean Ramón-Cueto and Manuel Nieto-Sampedro, then at the Cajal Institute in Madrid, got the OEC regeneration story rolling back in early 1990s with their paper, “
Regeneration into the Spinal Cord of Transected Dorsal Root Axons is Promoted by Ensheathing Glia Transplants.”
Within a few years many scientists jumped aboard, including such prominent investigators as Geoffrey Raisman in London and Mary Bunge in Miami.
In 1997 Raisman reported in
Science the recovery of forepaw motor function in adult rats with injured corticospinal tracts after transplantation of cells from olfactory bulb cultures. It was a pretty big story at the time; he told the New York Times, “I started working in this field 30 years ago and only in the last 12 months have we had this evidence of nerve fiber regeneration.”
(In press reports on the current dog study, Raisman said this: “This is not a cure for spinal cord injury in humans – that could still be a long way off. But this is the most encouraging advance for some years and is a significant step on the road towards it.”)
A year later Bunge, with Ramón-Cueto on her team, published
this finding:
Here, we report that pure EG transplants enhance the regenerative effect of SC-filled guidance channels and, very strikingly, promote long-distance axonal regeneration within the adult rat spinal cord after complete transection.
Numerous studies showed that OEC could get paralyzed rats moving again. It wouldn’t be long before nose cells were being put in people with spinal cord injury. By 2000 a doctor in Lisbon, Carlos Lima, now deceased, began operating on numerous patients, including a bunch of Americans. Because he based his procedure on the thinnest of pre-clinical data, he was not much esteemed, except by the people who paid him thousands of dollars for having their nose cells extracted, minced up and poured on to their exposed spinal cord. Yikes.
Did they get better? There was a lot of anecdotal chatter about gains in balance and sensory function, but no, Lima didn’t deliver functional recovery. He did publish some
results in 1996, based on seven patients:
“…two patients reported return of sensation in their bladders, and one of these patients regained voluntary contraction of anal sphincter. Two of the 7 ASIA A patients became ASIA C. Every patient had improvement in ASIA motor scores. … Adverse events included sensory decrease in one patient that was most likely caused by difficulty in locating the lesion.”
A more formal
human trial (the design included a control group which did not receive transplant surgery, and much more refined culturing of cells) took place in Australia. Six paraplegics got the treatment; while the cells were reported safe up to three years post-surgery – no tumors, no syringomyelia, no pain -- there were no significant functional changes in any patients.
More human trials are inevitable. A company called
Rhinocyte has plans to test human olfactory therapies for SCI, based on work by
Fred Roisen at the University of Louisville. The company has raised $5 million to date and is lookng to $10 million more; a proposal to begin trials is expected in the short term.
No question, these olfactory ensheathing cells remain a promising candidate for cell-therapy for spinal cord trauma. But back to the Jasper story. Co-author Robin Franklin, from the Wellcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, noted this: “Our findings are extremely exciting because they show for the first time that transplanting these types of cell into a severely damaged spinal cord can bring about significant improvement.”
How about this treatment for people? From the paper:
“ … the main implication of our study is that it does not provide encouragement to consider that olfactory mucosal cell transplants as a sole treatment would provide significant clinical benefit to human spinal cord injury patients.”
From the
Telegraph, a bit more clinical optimism:
“We’re confident that the technique might be able to restore at least a small amount of movement in human patients with spinal cord injuries but that’s a long way from saying they might be able to regain all lost function. It’s more likely that this procedure might one day be used as part of a combination of treatments, alongside drug and physical therapies, for example.”
From the paper, why the veterinary study is limited; it seems the cells might have activated automaticity and intraspinal stepping patterns but there was no recovery of axons that connect to the brain:
In this study, although we demonstrate that olfactory mucosal cell transplantation improves communication across the lesion, allowing recovery of ‘automatic’ coordination between forelimbs and hindlimbs, there are few data to support improvement of spinal long tract function. Human spinal cord injury patients most value recovery of arm, bladder and sexual function (Anderson, 2004), all of which are dependent on spinal long tract function, through which the brain is able to modulate lower motor neuron activity.
Therefore, although it would be expected that transplanting olfactory mucosal cells into human spinal cord injury patients would be associated with clinically detectable effects, it is improbable that patients would experience useful benefit in their everyday lives.
