Society for Neuroscience: Day 1

Twenty-fours travel (door to door) and setting up our exhibitors booth left just time to relax a little before the marathon Society for Neuroscience Annual Meeting, San Diego began in earnest. In this day and age of heightened security and baggage scanning it was somewhat amazing that a suitcase containing a plastic and metal, anatomically-correct sized, model of a spinal cord got through without questions. Well actually, our over overweight suitcase, had been “physically inspected” a little leaflet inside revealed – so faith restored in the US Department of Homeland Security.

Speaking of security, we had been warned there was a demonstration against research on animals planned to coincide with the first day. If I hadn’t known about it I would have walked right by without noticing it which is different from scenes I’ve witness in the UK in the past. But it does inspire me to blog at a later date on the use of animals in research as it is an important issue.

The meeting proper kicked off today with the first afternoon of poster presentations. Spinal cord injury research was amongst those topics represented during this first session in a series of posters devoted to plasticity. Plasticity of the nervous system plays an important role in the way the nervous system adapts to experience and injury. The myriad of connections between neurons of the nervous system are not entirely fixed and can and do change in response to stimuli. Understanding plasticity and manipulating it may offer one of the most promising avenues of repair for many conditions including SCI.

So it was good to get an opportunity to visit Leanne Ramer’s poster that presented some work that may shed light on two serious consequences/complications of SCI, namely pain and autonomic dysreflexia. Pain needs no explanation, but autonomic dysreflexia (AD) probably does. The autonomic nervous system controls parts and functions of the body that we take for granted and we are largely not aware of, such as heart rate, bladder function blood pressure etc. When it goes wrong, as in (AD), the consequences can be serious. SCI not only affects movement and sensation but also the autonomic system but it was not clear how. SCI stimulates plasticity in autonomic nervous system leading to new (inappropriate) connections into parts of the nervous system that are involved in sensation. The upshot being signals being sent from organs such as the bladder start to stimulate the autonomic nervous system dealing with things like blood pressure; bladder becomes too full, blood pressure sky-rockets. Ramer showed that in addition to this the sensory parts change and become more active, exacerbating the problem.

Has it really been a year?

Spinal Research heads off to the 40th Annual Society for Neuroscience Meeting in San Diego (13-17 Nov).

 

Look out for posts on research emerging in the field of spinal cord injury (and maybe beyond). You can also find other blogs covering the meeting.

If you're attending the meeting this year come visit our booth in the nonprofit section (Booth #3824)

Have embryonic stems cells had their day - already?

Yesterday's article on the Times online site gave voice to Thomas Okarma (CEO of Geron) who was making the case that embryonic stem cells are the only viable source of stem cell-based treatments. Geron, you may know, are preparing to enter clinical trials with the first human embryonic stem cell treatment in SCI. The ethical debate on the use of embryonic/fetal stem cells will probably not go away and for this and other reasons other sources of stems cells are being investigated. One of these is induced pluripotent stem cells (IPS) which is a technology that takes cells from the adult (say a skin cell) and drives these using biochemical and molecular biological techniques to become stem cell-like.

Okarma's argument is a simple one and goes; since it has taken tens of $millions to develop, produce and gain approval for the ES for their SCI trial, should it be necessary to replicated these costs for every patient-tailored treatment the costs and time would be unviable.

The article stimulates a very interesting debate. Obviously, Okarma sees medicine from a profit making angle. The current "product" they have ready to enter clinical trial in SCI will not break even financially and this hurts them and their shareholders. Nevertheless, they need to show the investment made so far was worth it and that the technology is medically viable. If they can do that they might have a chance of validating a platform which can be handle turned in other indications and recoup development costs and see a profit. The interview would have been given with more than half an eye on Geron's shareholders who probably want to be reassured new technologies such as IPS aren’t about to steal the market.

As ever the Americans (perhaps I'm being unfair) don't see beyond finance and assume there cannot be a non-profit approach that sees improving peoples’ lives as a motivation in itself. It also assumes that regulatory authorities will not change their own model of approval. The authorities are not there to impede science but to ensure the process safeguards the public. If this primary objective can be met by another model of regulatory approval that fits with "designer drugs" they will move towards that, eventually. But there will have to be justification, which can only be established by demonstrating what I call "advantages rather than features."

But let's not be naive. It will come down to what drives technology - heavily biased to financial reward at present - and what does the market want. These are often aligned, not always.

Things may shift: increasingly, the market involves government who are footing the bill for an ageing society and its associated ailments. Anything that can reduce the financial and socio-economic burden will be seen as a good thing and worth investing in. Right? The government's shareholders are the people and people don't demand a profit, just better lives. In this case, then, a profit does not have to be turned at the point of sale but later when measured in terms of well fare.

So, which is best ES or IPS? We can't know yet, but competition is a very good thing.

Unlocking the salamander's capacity to regenerate

The salamander has intrigued scientists for many years with its extraordinary capacity to regenerate after injury. Why is it and how do these animals manage to completely and faithfully regenerate large body structures such as limbs when mammals don’t?

In 2005, the respected journal, Science, declared that understanding what controls organ regeneration was in the top 25 hit parade of major questions facing scientists in the coming decades.

It seems the National Institute of Health in the US agrees and has awarded a $2.4 million package of funds to the University of Florida McKnight Brain Institute to stimulate research into this phenomenon as part of their Grand Opportunities (GO) program.

The multidisciplinary teams will embark on an examination of the salamander’s response to injury and systematically “compare and contrast” that with the human’s. Humans and other animals share many of the same genes but in the case of the salamander some of these genes may be regulated differently giving rise to useful regeneration. Using the cellular and genetic makeup of salamander to guide them they hope to understand what genes to switch on and off and ultimately unlock a far greater regenerative potential in patients.

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.

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.]