Tuesday 10 November 2009
Geron trial
Stem cells were in the news again. Geron will be hoping that the US Food & Drug Administration (FDA) will allow an expansion of the clinical trial using their human embryonic stem cell-derived oligodendrocyte precursor cells to include patients with cervical injuries. Previously, the FDA had given the go-ahead for recruitment of thoracic patients only as there was insufficient supporting data for efficacy in cervical injuries at the time. However, this week sees a paper published in the journal Stem Cells by Hans Keirstead’s group (University of California) who developed the original Geron stem cell line which might help change their mind.
Antifreeze .... anyone?
A fairly low-key story appeared in a number of media reports yesterday on the use of nanoparticles in SCI. The reports (e.g. http://abcnews.go.com/Health/wireStory?id=9028713) surfaced following the epublication of a paper in the journal Nature Nanomedicine.
The nanoparticles in question are made from a compound found in antifreeze – polyethylene glycol (PEG). PEG has been quite extensively investigated as a drug delivery vehicle as it forms tiny hollow spheres into which drugs can be captured giving the drug combo distinct and often useful distribution characteristics. However, the group behind this most recent paper have been working on PEG as a therapeutic in its own right and have been doing so for some while now. Indeed, as far back as 1999 there were reports of positive effects following administration of PEG in guinea pigs and more recently in dog patients.
One of the properties of PEG is its ability to integrate with cell membranes and it is suggested this helps to patch up damaged axons that have become leaky after an injury. This in turn reduces the amount of toxic agents entering injured axons after injury and in so doing protects them from further secondary damage.
So what's new? The latest report combines PEG with another compound called poly-lactic acid (PLA) which produces particularly small diameter spheres. The combination appears to work better than PEG alone.
By all accounts the protective effects of these polymers requires very early administration (within hours post injury) which may prove difficult to achieve clinically.
The nanoparticles in question are made from a compound found in antifreeze – polyethylene glycol (PEG). PEG has been quite extensively investigated as a drug delivery vehicle as it forms tiny hollow spheres into which drugs can be captured giving the drug combo distinct and often useful distribution characteristics. However, the group behind this most recent paper have been working on PEG as a therapeutic in its own right and have been doing so for some while now. Indeed, as far back as 1999 there were reports of positive effects following administration of PEG in guinea pigs and more recently in dog patients.
One of the properties of PEG is its ability to integrate with cell membranes and it is suggested this helps to patch up damaged axons that have become leaky after an injury. This in turn reduces the amount of toxic agents entering injured axons after injury and in so doing protects them from further secondary damage.
So what's new? The latest report combines PEG with another compound called poly-lactic acid (PLA) which produces particularly small diameter spheres. The combination appears to work better than PEG alone.
By all accounts the protective effects of these polymers requires very early administration (within hours post injury) which may prove difficult to achieve clinically.
Much to be learned from rehab
A number of interventions are now in early clinical trial and more are being proposed, yet there is a growing concern that existing measures to test efficacy may be inadequate, particularly if we accept that initial improvements may be poor (though still promising). Development of objective neurophysiological as well as functional measures has become an increasingly active area of research. Spinal Research recognised this some years ago and established its “Clinical Initiative” to address this need.
As part of this initiative, research funded by us at the Scottish Centre for Innovation in Spinal Cord Injury (SCISCI) in Glasgow has been specifically focused on developing outcome measures, the aim being to objectively study recovery following SCI whether it be due to natural recovery (i.e. spontaneous) and through any proposed intervention. Assessing neurophysiology – such as being able to measure changes in nerve conduction properties – may seem a tad esoteric to those only interested in practical and functional changes that represent improvements in quality of life, but if we understand more about how the two are related we will surely be better placed to discover the mechanisms of repair and importantly how to improve or optimise future treatments. We don’t want to throw the baby out with the bathwater.
The group from SCISCI presented two posters (SfN2009 Programme #542.7 & #741.9) at the recent Society for Neuroscience meeting in Chicago. They used Lokomat-driven Body Weight Supported Treadmill Training (BWSTT) as their test “intervention” and although primarily focused on developing outcome measures, one of the interesting findings of the study was that in acute patients (less than 6 months following injury) with incomplete SCI, the functional improvements seen with Lokomat were only significant during the first 3 weeks training, not beyond that. This has huge implications clinically as most research to date on BWSTT has adopted 8+ week rehab programmes and clinically there remains controversy over the optimum timing of initiation of rehab treatment. They suggest BWSTT performed for shorter periods such as 3 weeks and given early may benefit patients with incomplete SCI. Two other posters at the Society for Neuroscience (SfN2009 Programme #176.13 & #542.24) would seem to support this. In both, the beneficial effects of exercise in animals were observed within 3-4 weeks post injury. The animal studies and the clinical study at Glasgow, suggest BWSTT or exercises during the acute phase of SCI may facilitate recovery during a relatively short 3-4 weeks. Is there an optimal recovery window for interventions in the spinal cord injury common to both animals and humans and if so, what are the implications when planning future interventions in acute incomplete SCI subjects?
[My thanks to Dr Sujay Galen from the Scottish Centre for Innovation in Spinal Cord Injury who supplied the original report on which this post is based.]
As part of this initiative, research funded by us at the Scottish Centre for Innovation in Spinal Cord Injury (SCISCI) in Glasgow has been specifically focused on developing outcome measures, the aim being to objectively study recovery following SCI whether it be due to natural recovery (i.e. spontaneous) and through any proposed intervention. Assessing neurophysiology – such as being able to measure changes in nerve conduction properties – may seem a tad esoteric to those only interested in practical and functional changes that represent improvements in quality of life, but if we understand more about how the two are related we will surely be better placed to discover the mechanisms of repair and importantly how to improve or optimise future treatments. We don’t want to throw the baby out with the bathwater.
The group from SCISCI presented two posters (SfN2009 Programme #542.7 & #741.9) at the recent Society for Neuroscience meeting in Chicago. They used Lokomat-driven Body Weight Supported Treadmill Training (BWSTT) as their test “intervention” and although primarily focused on developing outcome measures, one of the interesting findings of the study was that in acute patients (less than 6 months following injury) with incomplete SCI, the functional improvements seen with Lokomat were only significant during the first 3 weeks training, not beyond that. This has huge implications clinically as most research to date on BWSTT has adopted 8+ week rehab programmes and clinically there remains controversy over the optimum timing of initiation of rehab treatment. They suggest BWSTT performed for shorter periods such as 3 weeks and given early may benefit patients with incomplete SCI. Two other posters at the Society for Neuroscience (SfN2009 Programme #176.13 & #542.24) would seem to support this. In both, the beneficial effects of exercise in animals were observed within 3-4 weeks post injury. The animal studies and the clinical study at Glasgow, suggest BWSTT or exercises during the acute phase of SCI may facilitate recovery during a relatively short 3-4 weeks. Is there an optimal recovery window for interventions in the spinal cord injury common to both animals and humans and if so, what are the implications when planning future interventions in acute incomplete SCI subjects?
[My thanks to Dr Sujay Galen from the Scottish Centre for Innovation in Spinal Cord Injury who supplied the original report on which this post is based.]
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