Update on Stem Cell Trials for Spinal Cord Injury
There is continuing positive news for the clinical trial being conducted by the company “Asterias” involving transplants of oligodendrocyte precursor cells (OPCs) derived from human embryonic stem cells. In this “Director’s Column”, I try to present things in a conservative and cautious way, but the latest news is really exciting and points back to fundamental discoveries here at the RIRC.
Readers of “Spinal Connections” know that the foundation for the Asterias trial was the paper in 2005 by Hans Keirstead at the RIRC (Keirstead, H.S., Bernal, G., Nistor, G., Totoiu, M., Cloutier, F., Sharp, K., and Steward O. Human stem cell derivatives remyelinate and restore locomotion after spinal injury. J. Neurosci., 25, 4694-4705).
After a lot of preclinical work, the clinical trial for oligodendrocyte precursor cells (OPCs) was launched by the company “Geron” and was the first ever trial for human stem cells for spinal cord injury. This trial was terminated for economic reasons and the company Geron folded but the company “Asterias” was founded and re-booted the trial with their product called “AST-OPC1”.
Since our last newsletter, the company has continued to provide interim reports on the results of the trial involving 6 subjects with cervical level injuries that had received 10 million OPCs (called “cohort 2”). These subjects had shown improvement in arm, hand and finger function at 3-months and 6-months following treatment, and the 9 month data showed more improvement. Then, just as we were finalizing this article in early October, Asterias released 12 month data on the 6 subjects in cohort 2. There was additional motor improvement so that 4 of the 6 subjects (67%) now exhibited at least two motor levels of improvement over baseline on at least one side and one achieved 3 motor levels of improvement on one side. This extent of recovery is higher than what would be expected based on independent data for historical controls. It’s important to emphasize that regaining two motor levels can improve ability to perform daily activities like feeding, dressing and bathing and reduce the overall level of assistance the person requires.
An article in the San Francisco Chronicle by Erin Allday quotes lead investigator, Dr. Richard Fessler, Professor of Neurosurgery at Rush University Medical Center: “Scientifically, I have to say we don’t know for sure if it’s the stem cells. But I’ve been treating these kinds of patients for 30 years, and I’ve never seen anything like this before.”
Although the current reports are very exciting, it’s important to keep in mind that the treatment being tested is only a start. If this was a computer application, you could think of this as version 1.0. The original science documented a measurable but modest improvement in motor function in rats, but with this as a start, we can move on to find better and more effective therapies (version 1.1, 1.2, etc.).
With an eye toward the need to develop more effective treatments in the future, it’s useful to look back at the roots of this story because it highlights the huge impact of private donations. The initial research by Dr. Kierstead’s group at RIRC was supported in part by private donations to our Center. One major finding in the original paper was that OPC transplants during the “acute” post-injury period improved function whereas transplants into rats with chronic injuries didn’t. We were able to do the study of chronically-injured rats because the animals had been generated for our summer boot camp “Techniques in Spinal Cord Injury Research”. We were able to maintain the rats into the chronic period because of private donations.
Private donations were critical for the initial pilot experiments that provided critical preliminary data for grant proposals. The first actual grant to support the work came from the “Roman Reed Spinal Cord Injury Research Act” and then Dr. Keirstead received a research grant in the initial round of funding by CIRM to support his stem cell research at RIRC. And of course, CIRM funding has been critical for the clinical trial by Geron and then Asterias.
To put all this in perspective, it’s worth remembering that when the RIRC was launched in 1999, there were no ongoing trials for people with SCI. We’ve come a long way and there is great optimism that we are on track for even greater advances. However, private donations are still the most important driving force for the first stage of innovation.
