- “I love it when a plan comes together.”
- Colonel John “Hannibal” Smith, The A Team
Posted: August 13th, 2014
There are times in life when everything seems to go wrong; then there are those (rare, for most of us) times, when things fall into place. There is no way to understand the “why” of these times, nor the when, but we can feel it when it happens.
UCSD announced this week that they were recruiting patients for Neuralstem’s upcoming chronic spinal cord injury trial. For this trial, “chronic” is defined as one to two years post injury. The patients will have an American Spinal Injury Association (AIS) grade A level of impairment. This means no sensory or motor function below the site of the injury. We have applied for a trial to treat acute injuries in Seoul, but the first trial in the U.S. will be limited to chronic injuries. With chronic SCI, we are actually counting on our cells to “rewire” the injured cord and reestablish a connection from above to below the injury. We have seen this very phenomenon in a study with our cells in rodent models with surgically transected spinal cords, which rendered them paraplegic, published in the peer-reviewed journal, CELL (http://www.sciencedirect.com/science/article/pii/S0092867412010185). But there is no real “chronic” animal model of spinal cord injury. Both ethical and practical limitations create a situation where only acute injuries can be studied and treated.
We are confident that our cells can in fact create new circuitry and allow for some signal to “bridge the gap” created by these injuries. But there was always a question we couldn’t get a handle on. Even if our cells allow the signal coming “down” the spinal cord to now get through the “break” area, will the circuitry leading “out” to the muscles still be intact and operational? In animals, it seemed clear that the answer was yes, but as mentioned those studies are always “acute” in terms of the time from the injury. There was simply no way to know what the situation was in humans a year to two years out from the injury.
Now however, there is good evidence that, in fact, that circuitry is still intact and operational. In a study reported in the April 8th, 2014 online neurology journal, BRAIN, researchers at UCLA and the University of Louisville demonstrated that chronic human SCI patients could have their lower limbs “activated” through epidural/electric stimulation. The results were extremely limited, but clear. The peripheral circuitry and muscle groups that were innervated were still capable of operating. This is very good news for our program. We now have the answer to the last “missing piece,” so to speak. We know now that if we CAN get the signal through the site of the injury back down to the rest of the cord, the remaining system has not atrophied past use. If this were not the case, then all the signal in the world coming “down” may not have provided a benefit for the patients. Now, there is every reason to believe that it can, and that this plan could indeed come together.
We are, of course, still very early in the process and, in this area in particular, there is a history of promising preclinical starts that have never translated into improvement in humans. So we must view the preclinical data with caution and some skepticism. But at Neuralstem we are not afraid to raise the bar on expectations. The first patient in this trial will hopefully be transplanted in September, and we hope to have all of the thoracic patients transplanted by the end of November, with a subsequent six-month observation period to collect data. This trial is now moving rapidly compared to our first ALS trial, in large part because of the safety data created in more than 30 spinal transplants in that ALS trial. It is, and has been, a long and sometimes bumpy road, but occasionally all of the pieces fit into place as you had planned; and, yes, it is nice when a plan comes together.
