Spinal re­search steps ahead for cure

A push to co-or­di­nate re­search into spinal cord in­jury may yield bet­ter re­sults, writes Bianca No­grady

The Weekend Australian - Travel - - Resources -

SU­PER­MAN was one of the rel­a­tively lucky ones. The fall from a horse that crushed ac­tor Christo­pher Reeve’s spinal cord may have robbed him of his abil­ity to walk, move or even breathe with­out help, but he still had money, and he had sup­port.

Un­like so many peo­ple in­ca­pac­i­tated by spinal cord in­jury, Reeve was sur­rounded by a car­ing fam­ily and sup­port, could af­ford the con­sid­er­able ex­pense of adapt­ing his home and life to his new cir­cum­stances, and was also a pow­er­ful, vis­i­ble cam­paigner for re­search into spinal cord in­jury.

It’s a far cry from the ma­jor­ity ex­pe­ri­ence of spinal cord in­jury vic­tims, most of whom are young men in­jured in ac­ci­dents.

‘‘ Th­ese guys are dev­as­tated,’’ says or­th­paedic sur­geon Ge­orge Owen. ‘‘ They can’t run, they can’t move, they feel their life is fin­ished — they just hide, fam­i­lies dis­solve around them and they go into a sec­ond-rate nurs­ing home.’’

Owen and wife Bar­bara are co-founders of Step Ahead Aus­tralia, for­merly the Spinal Cord So­ci­ety of Aus­tralia. Af­ter years of run­ning the or­gan­i­sa­tion on a shoe­string, Step Ahead last year en­tered into a three-year agree­ment with the fed­eral Gov­ern­ment, giv­ing the or­gan­i­sa­tion a man­date to co­or­di­nate re­search ex­per­tise fo­cused on find­ing a cure.

Step Ahead has also en­tered into a part­ner­ship with the Univer­sity of Melbourne and the city’s St Vin­cent’s Hospi­tal to set up a ded­i­cated spinal cord re­search lab­o­ra­tory.

There is plenty of Aus­tralian ex­per­tise to draw on. Aus­tralian re­searchers are in­ves­ti­gat­ing the use of hu­man bone mar­row stem cells, and the struc­tural ma­trix of skin and spinal cord, to bridge the gap of dam­aged tis­sue.

Spinal cord in­jury can be caused by trauma, such as a car and sport­ing ac­ci­dent, or a patho­log­i­cal process such as in­flam­ma­tion, a spinal cord stroke or dis­eases such as Guil­lain Barre Syn­drome. The com­mon fac­tor all th­ese con­di­tions have is the neu­ro­log­i­cal con­se­quences.

‘‘ It leads to var­i­ous de­grees of spinal cord dam­age, but the worst is com­plete dis­rup­tion of nerve fi­bres that come from the brain mak­ing the mus­cles work and also from skin, blad­der and so on up to the brain,’’ says Owen.

This can mean com­plete loss of mo­tor con­trol and sen­sory in­put from the rest of the body, leav­ing a per­son paral­ysed down­wards from the point of the in­jury.

The Owens know full well the dam­age done by the con­di­tion. At 14, their son Sam broke his neck in their swim­ming pool.

‘‘ It was dev­as­tat­ing be­cause I was very familiar with it,’’ says Bar­bara Owen, who had worked as a nurs­ing sis­ter at The Austin in Melbourne. ‘‘ I couldn’t be­lieve that I would have this in­jury in our back­yard.’’

In des­per­a­tion over the lack of sup­port for pa­tients with spinal cord in­jury, and the per­ceived ap­a­thy of the med­i­cal com­mu­nity, the Owens took mat­ters into their own hands. ‘‘ When Ge­orge and I started, it was our­selves who funded it, then Li­ons picked us up in the twi­light zone, when we were not big enough to be taken no­tice of but we were get­ting too big for Ge­orge and I to fund,’’ Bar­bara says.

That al­lowed their ef­forts to at­tract the at­ten­tion of the fed­eral Gov­ern­ment.

One of the re­searchers as­so­ci­ated with Step Ahead is Giles Plant, a lead­ing ex­pert in the field of spinal cord in­jury and head of the Reds Spinal Cord In­jury lab­o­ra­tory at the Univer­sity of West­ern Aus­tralia. He and his col­leagues are in­ves­ti­gat­ing a dou­ble-bar­relled approach to spinal cord re­pair that uses stem cells to re­build nerve con­nec­tions, and also tries to re­duce the ex­tent of the ini­tial dam­age and scar­ring.

Stem cells are the hot favourite to achieve sig­nif­i­cant gains in spinal cord re­pair. Be­fore his death in Oc­to­ber 2004 — nearly 10 years af­ter the horse-rid­ing ac­ci­dent that con­fined him to a wheel­chair — Christo­pher Reeve cam­paigned heav­ily in favour of stem cell re­search.

Un­like the more con­tro­ver­sial em­bry­onic stem cells, Plant is in­ves­ti­gat­ing the use of au­tol­o­gous adult bone mar­row stem cells — stem cells taken from the pa­tient them­selves.

‘‘ The beauty of this is that it shouldn’t get re­jected be­cause it’s from the pa­tient’s own body,’’ says Plant.

The first chal­lenge, how­ever, is to sin­gle out the right type of cell. ‘‘ The big­gest prob­lem we’ve got in the trans­plan­ta­tion field is if you have a num­ber of dif­fer­ent cell types in the in­jury zone, and we don’t know what the com­pli­ca­tions are go­ing to be long-term.’’

In this case, re­searchers are aiming for the bone mar­row stro­mal stem cells — the pro­gen­i­tor cells for var­i­ous skele­tal tis­sue com­po­nents such as bone, car­ti­lage and fat cells. Ex­per­i­men­tal ev­i­dence so far sug­gests th­ese stem cells can also be in­duced to dif­fer­en­ti­ate into other cell types, such as neu­ral cells. The idea is to in­ject the pu­ri­fied stem cells into the dam­aged site, where they pro­mote re­pair of dam­aged nerves and per­haps en­cour­age the for­ma­tion of new con­nec­tions to re­place those lost. Early stud­ies in rats have been promis­ing.

‘‘ We’ve got a lot of very good re­sults in terms of be­havioural re­cov­ery,’’ says Plant. This re­cov­ery is mea­sured by their abil­ity to sup­port their own weight and as­pects of their walk­ing pat­terns.

The re­searchers are also find­ing ways to en­cour­age the body’s own re­pair mech­a­nisms into ac­tion, us­ing viruses to mod­ify the stem cells so that they can se­crete fac­tors that are known to be pref­er­en­tial for re­pair­ing the spinal cord.

While stem cells are the flavour of the year in spinal cord in­jury re­search, as well as many other ar­eas of medicine, Plant be­lieves it’s go­ing to take a multi-pronged approach to tackle the prob­lem.

‘‘ We’re never go­ing to have a one-cell won­der — a sin­gle wal­lop that cures all,’’ Plant says. ‘‘ We’re try­ing to approach from the point of view that maybe three or four dif­fer­ent tar­gets will be the way to go.’’

An­other one of those tar­gets is be­ing stud­ied by Kathy Tra­ianedes, se­nior sci­en­tist at the Aus­tralian Stem Cell Cen­tre in Melbourne. In this case, rather than in­tro­duce stem cells to re­gen­er­ate a dam­aged area, Tra­ianedes and col­leagues are in­ves­ti­gat­ing the use of the bi­o­log­i­cal ma­trix to re­cruit cells into the dam­aged area to re­pop­u­late and re­pair the area. The bi­o­log­i­cal ma­trix is ef­fec­tively the tis­sue struc­ture in which cells live and de­velop: struc­tural pro­teins, col­la­gens, growth fac­tors and other bi­o­log­i­cal com­po­nents; ev­ery­thing ex­cept the cells them­selves.

Ev­i­dence sug­gests if all the right com­po­nents are there, the ma­trix ac­tively re­cruits stem cells, pos­si­bly from the blood sup­ply, to re­pop­u­late the area.

‘‘ If you can take a bi­o­log­i­cal ma­trix, re­move all the cells and put it back into its func­tional area where it’s meant to be, the­o­ret­i­cally the right cells would know what to do when they get there,’’ Tra­ianedes says.

Der­mal ma­trix in the skin is al­ready be­ing used to re­gen­er­ate soft tis­sue deficits, in­clud­ing from burns. Other re­search has also found that when im­planted into a dif­fer­ent part of the body it can take on the char­ac­ter­is­tics of the ma­trix nor­mally found in that new area. In her re­search, Tra­ianedes is us­ing spinal cord ma­trix wrapped in der­mal ma­trix, which it is hoped will pre­vent scar tis­sue from the in­jury grow­ing into the breach.

‘‘ We’re hop­ing to see a pro­gres­sion of po­ten­tially new blood ves­sels form­ing and mi­gra­tion of cells into the site and hope­fully a link­ing of two ends of the trans­acted cord,’’ Tra­ianedes says.

How­ever, Plant is cau­tious about what all this re­search can achieve, ar­gu­ing it is go­ing to be very dif­fi­cult for science to be able to com­pletely re­store spinal cord func­tion.

‘‘ I don’t think we’ll get some­body com­pletely cured,’’ he says. But a more re­al­is­tic goal is to im­prove a per­son’s in­de­pen­dence, al­low­ing them such small but sig­nif­i­cant gains as be­ing able to feed them­selves, clothe them­selves, re­cover blad­der and bowel func­tion and not have to rely on con­stant care. The long-term goal would al­ways be to get them walk­ing again, he says.

While this re­search is still in its early stages, Step Ahead’s co-founders are ex­cited about the prospect of re­search such as this be­ing given the op­por­tu­nity to move into the clin­i­cal set­ting.

‘‘ We can do end­less lab work, but if it’s not co-or­di­nated, that’s where it sits,’’ says Bar­bara Owen. ‘‘ We need a treat­ment as soon as pos­si­ble pro­vided it is eth­i­cal and ev­i­denced-based, but there has to be a leap of faith from the lab­o­ra­tory model to the hu­man ap­pli­ca­tion.’’

Pic­ture: Stu­art McEvoy

Man­date to move for­ward: Ge­orge Owen and his wife Bar­bara are ex­cited about the progress of spinal cord re­search

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