With the passing of Christopher Reeve, his appearance this election season in a television ad aired in California asking viewers to "stand up for those who can't" was both eerie and poignant. "Stem cells are the future of medicine," he said.

In the commercial, Reeve, who was paralyzed in a 1995 horse-riding accident and died in October, urged Californians to support Proposition 71 - the California ballot initiative that would give $3 billion in state funding over 10 years for stem cell research. Although Reeve was more than 40 years old when he was injured, according to materials from the Society for Neuroscience, nearly half of the 11,000 annual new cases of spinal cord injuries occur in persons aged 16-30.

The initiative was voted in, but it's worth noting that stem cells are only one of the avenues being explored in the hopes of eventually curing paralysis. At the 2004 Neuroscience meeting, in fact, some of the biggest excitement in paralysis research was generated by developments on the device side - so-called brain-computer interfaces, which use recordings of brain activity to directly control gadgets from robotic arms to computers.

But research on the therapeutics side also is active. Both academic and commercial groups reported at the meeting on efforts to neutralize the effects of neural growth inhibitors after spinal cord injury. Growth inhibition is the bane of researchers who want to induce regeneration in the central nervous system of mammals. The problem is that while it's comparatively easy to get either the mammalian peripheral nervous system or the central nervous system of amphibians, for example, to regenerate after injury, the mammalian central nervous system is full of molecules on a mission to thwart severed neurons' goal to reconnect with former targets.

Those inhibitors derive from two main sources: myelin debris, which result from spinal cord neurons' insulation being crushed in an injury, and the so-called glial scar, which forms in response to injury. One inhibitor currently receiving a lot of attention is chondroitin sulfate proteoglycan, which consists of a protein core and carbohydrate side chains. The enzyme chondroitinase can be used to snip off those side chains, which are responsible for the molecule's inhibitory effects. In 2002, the effectiveness of chondroitinase in promoting functional recovery after spinal cord injury first was described, and the enzyme has been under the microscope, as it were, ever since.

Publishing up a storm at Neuroscience was Acorda Therapeutics Inc., of Hawthorne, NY, which presented 10 abstracts - alone and with academic collaborators - on spinal cord injury research. Half of those were on chondroitinase, which Acorda is producing recombinantly in E. coli. The company hopes that will have several advantages over bacterially derived chondroitinase; for one, production in E. coli is more cost effective than purification from Proteus vulgaris, the bacterium that normally makes the enzyme. Acorda scientists also hope they will be able to produce "mutant enzymes with beneficial properties, such as reduced size and enhanced activity," Tony Caggiano, senior scientist at Acorda, who also presented at Neuroscience, told BioWorld Today. The company presented posters showing several such mutants, as well as in vitro evidence that they retained activity.

Acorda also presented behavioral studies that demonstrated a beneficial effect of chondroitinase on both somatic and autonomic motor function. Chondroitinase was able to improve both locomotion and bladder control in rats with moderate to severe spinal cord injury. When the injury was milder, no improvement was seen, though Caggiano believed that might be more a function of the fairly crude behavioral tests used. He also said evaluation of more subtle parameters might show improvements after milder injuries. He said the company hopes to take recombinant chondroitinase into the clinic in the next 12 to 18 months.

Cocktail Hour For Injured Spinal Cord Neurons

There was a lot of attention for Dennis Stelzner, professor of cell and developmental biology at SUNY Upstate Medical Center in Syracuse, N.Y., and his colleagues at the meeting. His poster, seen through a throng of interested viewers, provided a glimpse of how nanotechnology might be used to combine different therapies for best overall effectiveness. Stelzner and his group used PLGA nanospheres to deliver chondoitinase directly to the glial scar. In the poster, the scientists demonstrated that by varying different nanosphere properties, they could control different aspects of drug delivery. Manipulation of the surface charge caused the nanospheres to attach directly to their target, chondroitin sulfate proteoglycan. In cell culture, the loaded nanospheres were able to destroy inhibitors and allow neurons to grow.

The nanospheres boast the capabilities of being able to be loaded with different substances and configured to degrade at different rates. "From my perspective, what's most interesting, is that we can incorporate whatever we want and have it be released at different times," Stelzner told BioWorld Today. "If you walk around here, you'll see a dozen different things that will give you a little bit of axonal growth. But none of them by themselves are all that good. We hope that by combining them, we can make a cocktail that will maximize axonal growth."