Research: walking the dog

Granger N, Blamires H, Franklin RJ, Jeffery ND. Autologous olfactory mucosal cell transplants in clinical spinal cord injury: a randomized double-blinded trial in a canine translational model. Brain. 2012 Nov;135(Pt 11):3227-37. doi: 10.1093/brain/aws268.

This study was designed to determine whether an intervention proven effective in the laboratory to ameliorate the effects of experimental spinal cord injury could provide sufficient benefit to be of value to clinical cases. Intraspinal olfactory ensheathing cell transplantation improves locomotor outcome after spinal cord injury in 'proof of principle' experiments in rodents, suggesting the possibility of efficacy in human patients. However, laboratory animal spinal cord injury cannot accurately model the inherent heterogeneity of clinical patient cohorts, nor are all aspects of their spinal cord function readily amenable to objective evaluation. 

Here, we measured the effects of intraspinal transplantation of cells derived from olfactory mucosal cultures (containing a mean of ∼50% olfactory ensheathing cells) in a population of spinal cord-injured companion dogs that accurately model many of the potential obstacles involved in transition from laboratory to clinic. Dogs with severe chronic thoracolumbar spinal cord injuries (equivalent to ASIA grade 'A' human patients at ∼12 months after injury) were entered into a randomized double-blinded clinical trial in which they were allocated to receive either intraspinal autologous cells derived from olfactory mucosal cultures or injection of cell transport medium alone. Recipients of olfactory mucosal cell transplants gained significantly better fore-hind coordination than those dogs receiving cell transport medium alone. 

There were no significant differences in outcome between treatment groups in measures of long tract functionality. We conclude that intraspinal olfactory mucosal cell transplantation improves communication across the damaged region of the injured spinal cord, even in chronically injured individuals. However, we find no evidence for concomitant improvement in long tract function.

New research from the lab of Prof Franklinstein (Robin Franklin from Cambridge and Colleagues) showing that dogs with spinal injuries can get some benefit following transplantation of olfactory ensheathing cells can facilitate some nerve regrowth. This has made a media splash in the UK and so for people who have not seen it

Although nerves are though not to regenerate you are constantly making new nerve connections in your nose. The olfactory ensheathing cell is a type of glial cell that can facilitate remyelination and can facilitate nerve growth . The nose contains neurons that send signals to the brain when triggered by odor molecules. The axons of these neurons are enveloped by OECs that guides the axons and supports their elongation. The bundles travel from the nose to the brain’s olfactory bulb, where they make connections with other neurons. Because olfactory tissue is exposed to the external environment (i.e., the air we breathe), it contains cells with considerable regeneration potential, including renewable neurons, progenitor stem cells, and OECs. Through a relatively innocuous biopsy procedure, olfactory tissue can be obtained from the nasal cavity. It can also be retrieved from the olfactory bulb, but this requires an invasive penetration of the cranial cavity making it harder to do in humans than dogs.

See the Dog (Jasper) walk and read the comments and cautionary notes so as we do not get too excited but it is very encouraging. I note that the tail of Jasper was not paralysed so not sure how much spinal cord was affected, but there was improvement in, I guess their star, sausage (dog) and they got improvement in the others. It was demonstrated that olfactory mucosal cell transplantation improves communication across the lesion, allowing recovery of ‘automatic’ coordination between forelimbs and hindlimbs.

In this case they were transplanted in to dogs that had got nerve damage. There were improvements in many as they had facilitated nerve growth and this could have functional benefit. Similar benefits have been reported in spinal cord damaged rats, but moving up to bigger species is more technically challenging but more rewarding with the hope that this can be developed for humans, however it should be noted that the procedure was not without its problems and 10% of our four-legged friends didn't make it. The authors also point out that they believe this is only part of the answer for treating the human condition. It is open access so you can have read if you like.

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