Almost a year after the FDA halted the study, Geron‘s clinical trial for a human embryonic stem cell (hESC) therapy for spinal cord injury is back on track. The Silicon Valley biopharm company recently announced that it had satisfactorily addressed the FDA’s concerns about cysts formed in animal models of the treatment that had stalled the trials. While the year delay was a serious setback, Geron’s pursuit of spinal cord injury repair is still the most advanced hESC therapy being tested in humans. While it is only in phase I of clinical trials, Geron’s hESC therapy carries the promise of at least partially healing paralyzed patients. This is the kind of research that Christopher Reeves and so many others advocated for, and it is finally moving forward again.
Geron is building off of Hans Kierstead’s amazing work at UC Irvine. In animal studies, researchers were able to get rodents with induced spinal injuries walking again. Think about it, a rat with a huge lesion on its spinal cord can’t move it’s hind legs, but after embryonic stem cell therapy it regains most of its mobility. Here are two videos that showcase these incredible results. The first is an explanation by Kierstead and the second is a brief look at a rat before and after treatment. Awesome!
We won’t know how powerful the Geron hESC treatments will be until they’ve undergone clinical trials, which is why getting those trials underway is so important. As we discussed in September of last year, the FDA had stalled Geron’s clinical trial for GRNOPC1 (the hESC spinal cord injury therapy) due to the formation of cysts in some of the rodents treated in preliminary studies. While these cysts were microscopic, seemed benign, and were quite ordinary for spinal injuries, the FDA didn’t want to take any chances. Over the past year, Geron has gone back to these animal studies and developed new techniques and approaches to minimize the formation of these cysts. According to their recent press release, Geron has developed new molecular markers and release assays and performed additional animal studies that demonstrate lower numbers of cysts. The FDA is now more satisfied with GRNOPC1 and permitted Geron to continue its groundbreaking human trials.
That phase I trial will be primarily focused on safety, and has a rather limited patient pool. Only those with severe nerve injury and likely to demonstrate grade A impairment (as defined by the American Spinal Injury Association) will be enrolled. Those treated in the trial will receive hESC as injections seven to fourteen days after injury which is a pretty short window. Geron has yet to release the names of the half dozen or so medical institutions where the trials will take place, but says that information is likely to come online soon. It looks like, however, that given the short window of possible treatment, and the strict guidelines for patient selection, that those with premeditated interest in joining Geron’s study are unlikely to be accommodated in phase I. In other words, if you already have a spinal injury you’re not going to be involved in this part of the trials. Perhaps that will change as they move from safety to efficacy (in later phases…likely years from now).
The long term potential of these trials, however, is very promising. The Geron study stands out even among other stem cell trials because of the capacity for healing nerve damage. In the trials, human embryonic stem cell derived glial progenitor cells will be injected directly into lesions along a patient’s spinal cord. Animal models indicate that the glial progenitor cells should work to promote nerve growth and repair the myelin sheaths on the nerves. This ‘remyelination’ of the nerves is a critical component of healing spinal cord injury as it allows signals to be passed along the nerve. Here’s a video animation that explains more:
Damaged myelin, however, is not unique to spinal cord injuries. It plays a crucial role in multiple sclerosis and Geron is moving towards non-human primate studies for MS using GRNOPC1 (or similar hESC therapy). Additionally, Geron has stated it is researching treatments for Alzheimer’s disease (animal models) and Canavan disease (rodent models). Although we have seen a promising MS treatment that could be ready much sooner than a hESC technology, if Geron could develop therapies for any of these conditions it would be a major breakthrough.
Despite the range of possible applications Geron seems primarily focused on treating spinal cord injury. Rightfully so. There are few uses for hESC that are as noble or as awe-inspiring as getting a paralyzed person to walk again. Of course not even Geron is claiming that their GRNOPC1 treatment will be able to produce that kind of result, but it’s probably on everyone’s mind when they hear stem cells and spinal cord injury in the same sentence. The extent to which hESC will actually be able to treat spinal injury is a great unknown. Animal tests had rodents regaining the control over hind legs after treatment, but that was under very controlled conditions (and not in humans, clearly). It will likely be years before we know the full efficacy of GRNOPC1. A lot may hinge on Geron’s eventual success – if they face too many more regulatory delays or don’t develop a marketable product it may discourage other companies from investing in hESC therapies. Even with the pressure this is a very exciting time. The world’s first human trials for embryonic stem cells are back on track. Let’s hope they produce great results soon.