“I would have predicted Parkinson’s disease was going to be our first goal,” Lebkowski says today. The protocol seemed straightforward enough: Grow ES cells; steer them to yield dopamine-producing cells, the brain cells ravaged by Parkinson’s; and then transplant those cells into the appropriate brain regions. Researchers transplanting stem cells into Parkinson’s animal models weren’t demonstrating “terribly good results,” however, Lebkowski recounts. That’s when a new partnership emerged, along with a new direction in research. 

 

Hans Keirstead at UC Irvine’s Reeve-Irvine Research Center was getting positive results when he implanted OPCs into the spinal cords of rats. Keirstead, a neurobiologist who did his postdoctoral training at Cambridge University, is one of the scientists who originally demonstrated that injury to the spinal cord is accompanied by a significant loss of the myelin that sheathes axons. He realized that no matter how many neurons had been severed at the injury site, axons off to the side sometimes escaped injury, although they were missing their myelin and couldn’t function. Hence Keirstead’s goal of re-sheathing them. It wasn’t long before Geron formed a working relationship with Keirstead, whose lab ended up the glad recipient of funds from both Geron and the University of California’s grant-matching BioSTAR program. 

 

Results from testing their OPCs on lab rats with paralyzed hind limbs “are big enough to spur you on to humans,” says Lebkowski. Before treatment, they drag their hind legs. When injected with human OPCs seven days after the injury, they can plant their hind legs and support themselves as they move about. Scans of the animals validate that axons denuded of myelin have indeed been re-sheathed, says Gabriel Nistor, a postdoctoral researcher in Keirstead’s group. Remyelination isn’t the only factor that appears to benefit the rodents. The transplanted cells, Nistor says, also “secrete growth factors that can rescue some neurons from dying.”

 

 

Geron’s expectations for its human trials are fairly modest. “What we’re looking for isn’t necessarily that everyone is going to get up and walk,” notes Lebkowski. “But if you could improve even just one level of spinal function, especially in someone with a cervical [neck] injury, it could make a big difference.” Reducing a patient’s impairment by just one spinal column segment might re-establish some small hand or arm movement, restore a bit of bladder control, or improve some portion of heart or lung function. It’s been said about Christopher Reeve, for instance, who sustained his injury high in the cervical region, that had he regained one level of function, he might have been able to dispense with his ventilator.