Take time to draw breath

Application of the bacterial enzyme, chondroitinase, led to restoration of breathing even after long term paralysis of the diaphragm, it was revealed at a press event at the annual Society for Neuroscience meeting. Philippa Warren, a Case Western Reserve scientists and lead on this work, described how the paralysed diaphragm recovered function after a remarkable 1.5 years post injury. "This treatment holds great promise for those with respiratory dysfunction", said Warren. Case Western's own press release can be read here.

A subsequent poster [#523.10] expanding on her work revealed that some of the animals treated responded perhaps too well to the treatment resulting in a less than rhythmic pattern of muscle contraction. Investigation showed that there was particularly strong reactivation of excitatory nerve fibres and that recovery and function in these was likely to be responsible for the recovery. Indeed, treating with a drug that could interfere with signals from these fibres brought things back in line.

Elsewhere, Kevin Hoy was reporting similar (respiratory) recovery after treatment with a licensed anti-cancer drug[#523.08]. Taxol is used in chemotherapy and stabilises the cellular scaffolding in cells. At low doses, however, the stabilisation appears to make for a more robust growth response in nerve fibres. Taxol is by its nature toxic but the dose used in these studies was 1/100 that used clinically. Nevertheless, Hoy looked at whether a less toxic drug with similar properties also led to recovery of breathing function. Alas, no but further work does need to be done, he said.

I was also impressed with Caitlin Hill's study [#523.26]. We know that cellular grafts often survive poorly and efficacy is disappointing. The question Hill set out to answer was; is the lack of effect due to poor choice of cells or simply due to so much cell death which in and of itself has a negative impact on the outcome? It's a subtle question but potentially an important one to answer given the shear amount of effort going into cell transplantations these days.

Lessons to be learned from other fields?

It is time for another Society for Neuroscience meeting. Washington this year and it's cold and drab - feels like home. It's a slow start with most of the sessions devoted to spinal cord injury yet to come. Nevertheless, brain computer interfacing (BCI) dominated the afternoon's posters so why not take look here [Neuroprosthetics; BCI].

Without a specific session devoted to SCI there is the opportunity to look elsewhere. Amongst rows of poster on demyelinating disorders (for example, multiple sclerosis) I came across work by M Keough (University of Calgary, Canada) [#224.18]. Over the years much has been written about chondroitin sulphate proteoglycans (CSPGs) and their involvement in scar formation after SCI. CSPGs inhibit axonal growth and regeneration and are a major therapeutic target for repair. Treatment with the bacterial enzyme chondroitinase ABC - which digests CSPGs - and more recently treatment with inhibitors of the receptor for CSPGs, have shown positive effects.

CSPGs also interfere with cells called oligodendrocyte precursor cells which are involved in remyelination of axons. For diseases such as MS as with SCI, CSPGs interfere with potential repair and recovery so Keough and colleagues asked this simple question; what if we stop the formation of CSPGs? Since CSPGs are formed by the stepwise addition of multiple glucosamine subunits, introducing a subunit that cannot be added to may inhibit the formation of long mature CSPG chains. Fluorosamine is in every way identical to the natural subunit that are needed for the formation of CSPGs except for the presence of a single fluorine atom in the place of one of the carbon atoms in its structure. Treating scar-forming cells (astrocytes) in culture with fluorosamine reduced the amount of CSPGs formed whilst not affecting their viability. They went on to show benefits in an experimental model of demyelinating disease.

It will be interesting to see if this work is picked up by the SCI research community.