The functional effects of olfactory ensheathing cell transplantation on severe clinical spinal cord injury in dogs

Lead Research Organisation: University of Cambridge
Department Name: Research Services Division

Abstract

This project will determine whether transplanting a special type of cell improves the outcome after severe spinal cord injury (SCI) in dogs. These dogs will be veterinary patients – domestic dogs that have incurred SCI during their life as pets. Veterinary treatment of spinal cord injury (SCI) in dogs is very similar to that in humans, and similarly limited in its ability to restore lost function.

We will transplant olfactory ensheathing cells (OEC), which are found in the parts of the nervous system that deal with olfaction (smell) and allow re-growth of previously damaged nerve fibres in the spinal cord, which normally does not happen. Their beneficial effect on recovery after experimental SCI in laboratory rats has been shown on numerous occasions but we now need to determine whether the effect in lab animals can be duplicated in real-life clinical injuries.

This study in canine patients provides a missing link between experimental results in lab animals and the human clinic. The results of this project will be critically important for determining whether to go ahead with a human trial and will also provide important information for understanding how the spinal cord responds to injury.

Technical Summary

Although intraspinal transplantation of olfactory ensheathing cells (OECs) has been associated with a beneficial effect on functional outcome after experimental spinal cord lesions in laboratory rodents there are several reasons why this effect cannot be taken for granted if it were to be translated into human spinal cord injury (SCI). This is partly because clinical lesions differ greatly in size and pathogenesis from experimental lesions in rodents. More importantly, clinical categories of SCI, no matter how they are defined, are heterogenous ? containing lesions of varying histological type and severity, meaning that small treatment effects may become lost in the ?noise? of clinical variability.

SCI is a common clinical problem in dogs and there is a cohort of severely affected individuals in which conventional treatment fails to restore adequate function ? forming a suitable population for assaying the value of putative therapies for clinical SCI in humans. We have previously established that autologous OECs can be harvested, multiplied in vitro and transplanted into such affected dogs without evidence of detrimental effects. In this current project we will compare the efficacy in restoring lost function between: a) intraspinal OEC transplants, and b) intraspinal injection of cell transport medium alone. Treatments will be randomised and the outcome measures will be determined by a masked observer. We will focus on: i) analysis of data produced by digitising the gait of dogs as they walk on a treadmill, permitting quantification of the inter-relationship between movement cycles of different limb pairs - and many other parameters, and ii) measurements of the effects on bladder filling and detrusor ? sphincter mechanism coordination using cystometry.

The results of this study will have profound implications for future clinical trials on OEC transplantation in humans, its potential as a clinical treatment modality and also provide greater understanding of the response capabilities of the injured spinal cord. In the long term, this extension of the ?dog model? of human SCI will provide a highly clinically relevant means of testing future laboratory-derived putative therapies for SCI prior to human clinical trials.

Publications

10 25 50
 
Description Frank Litchfield Charitable Trust Equipment fund
Amount £15,876 (GBP)
Organisation Frank Litchfield Charitable Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2009 
End 09/2011
 
Description University of Cambridge Isaac Newton Trust Grant
Amount £17,071 (GBP)
Organisation University of Cambridge 
Department Isaac Newton Trust
Sector Academic/University
Country United Kingdom
Start 06/2010 
End 09/2011
 
Description National and local TV, national and local radio, national press 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact We provided an outline of our project to local TV - one of our clinical trial participants had media contacts and we wished to publicise the trial to gain as many subjects as we needed. This was followed up by interest from national radio (I was interviewed live) and national newspaper reports.
There was a further report in the local newspaper about the study in 2010.

When the Brain paper there was extensive press coverage following press release by MRC press office. For example:

Channel 4
http://www.channel4.com/news/paralysed-dog-breakthrough-offers-hope-for-humans

ABC
http://abcnews.go.com/Health/nose-cells-paralyzed-dogs-walk/story?id=17763218#.UKtB66JKRM0

ITV Anglia
http://www.itv.com/news/anglia/story/2012-11-19/paralysed-dog-walks-again/

CNN
http://edition.cnn.com/video/?hpt=hp_c3#/video/bestoftv/2012/11/20/sproj-paralyzed-dogs-walk-again-max-foster-pkg.cnn

ITN
http://www.itn.co.uk/UK/61951/paralysed-dog-walks-after-pioneering-research

BBC News
http://www.bbc.co.uk/news/health-20390966

Hope for the paralysed as dogs helped to walk again (Daily Telegraph)
http://www.telegraph.co.uk/health/healthnews/9687253/Hope-for-the-paralysed-as-dogs-helped-to-walk-again.html

Time for walkies! Pet dogs paralysed by spine damage are able to walk again following pioneering treatment (Daily Mail)
http://www.dailymail.co.uk/sciencetech/article-2235028/Scientists-reverse-paralysis-dogs-following-pioneering-cell-treatment.html#ixzz2ClIzZEOY

"It's utterly magic": Paralysed dogs walk again after NOSE cells are used to fix spinal breaks - video (Daily Mirror)
http://www.mirror.co.uk/news/technology-science/paralysed-dogs-walk-again-after-1444971

Paralysed dog walks again after nose cells treatment - video (Guardian online)
http://www.guardian.co.uk/science/video/2012/nov/20/paralysed-dog-nose-cells-video

Paralysed dog breakthrough offers hope for humans (Channel 4)
http://www.channel4.com/news/paralysed-dog-breakthrough-offers-hope-for-humans

Jasper the paralysed dog is walking again (BBC News)
http://www.bbc.co.uk/news/health-20390966

Jasper's story carries hope for thousands of people with spinal injuries (Cambridge News)
http://www.cambridge-news.co.uk/News/Jaspers-story-carries-hope-for-thousands-of-people-with-spinal-injuries-20112012.htm

Dogs raise hopes for paralysed humans (New Zealand Herald)
http://www.nzherald.co.nz/lifestyle/news/article.cfm?c_id=6&objectid=10848746

Cell cure: Paralysed dogs walk again (Times of India)
http://timesofindia.indiatimes.com/home/science/Cell-cure-Paralysed-dogs-walk-again/articleshow/17288396.cms

Dog spinal study may provide clue for humans (ABC News)
http://www.abc.net.au/news/2012-11-20/dog-spinal-study-may-provide-clue-for-humans/4381272





The early exposure was successful in increasing our ability to recruit participants. It remains to be seen how the extensive press coverage when our trial paper was published will impact on this field but it is to be hoped that it will help validate the dog as translational model for SCI, and perhaps veterinary species as translational models more generally.
Year(s) Of Engagement Activity 2009,2010,2011,2012
 
Description Richard Bunge Memorial Lecture (University of Miami) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An annual lectureship was established for the Neuroscience Program at the University of Miami in memory of Richard Bunge. Students and researchers attended.
Year(s) Of Engagement Activity 2014