About that Hold

Geron has revealed the reason for the FDA hold on its Spinal Cord Injury Investigational New Drug application. In an August 27th press release, Geron scientists revealed that the implanted GRNOPC1 cells caused cysts in a small proportion of the animals injected with them. These cysts were not cancerous. The report calls them “non-proliferative,” which simply means that they are not growing. Additionally. the cysts are very small – microscopic in size. Finally, the cysts were confined to the region of the injury and did not adversely affect the laboratory animals.

Why the hub-hub? A recent animal study reported a greater frequency of cysts. Once again, they are non-proliferative (non-growing), restricted in location to the site of injury and do not affect the animals.

What’s going on? Cyst formation is common in spinal cord injury. Once the spinal cord is injured, inflammation ensues and this involves the invasion of the spinal cord by immune cells that mop up the dead cells and debris from the injury. Unfortunately, immune cells are sloppy eaters and they do a great deal of damage to the spinal cord. The damage they cause also tends to summon more immune cells, which come to the scene of the injury and damage the spinal cord even more. the whole thing is a positive feedback mess.

To put an end to it the spinal cord makes a plug called a glial scar. The glial scar comes from the stem cell population in the spinal cord. These stem cells form support cells called “glial cells” and these cells plug the hole in the spine and shut out the immune response, thus saving the spinal cord. The formation of this glial scar, however has a severe downside for spinal cord regeneration: the glial scar is loaded with chemicals that repel growing neurons. Therefore, those neurons that were severed by the injury could not regrow their extensions if they wanted to. The glial scar acts like a bunch of burly security guards that prevent the neuronal extensions from getting to the other side.

These cysts are probably the result of the GRNOPC1 cells forming tiny glial scars to help the injured spinal cord heal. Now they do not seem to affect the laboratory animals, but they are inhibitors of neuronal healing. Therefore, while they may not affect the laboratory animals, they may represent a fix that sentences the spinal cord to never being fixed by anything else again.