Posted on January 15th, 2013
by Richard Garr
“The accident was a horrible thing – but that horrible thing made Chris, at the end of his life, Superman. It’s a happy irony if there is such a thing. I’m proud to have known him.”
Yesterday, Neuralstem announced that the FDA approved our spinal cord injury trial (SCI). It’s hard not to think of Chris Reeves at a time like this. I actually met him once, at a dinner party in London in 1979. He was filming the second Superman movie, a remarkably quiet and unassuming young man given his enormous physical gifts and burgeoning fame. That he is synonymous now with the effort to cure spinal cord injury is a tribute to the efforts he put into his foundation’s work from the time of his accident until his death.
Our approved trial is a Phase I trial to treat chronic spinal cord injury. For this trial, chronic is defined as one to two years out from the injury. The patients will be “complete” paralysis patients, which means no sensory or motor function from the point of the injury “down.” We will not be treating cervical injuries (the type Christopher Reeves had) in the first group of patients, but thoracic injuries; think of it as from the chest down. As with our ALS trial, the FDA would like us to establish the safety of our surgical route of administration in the back below the cervical region before moving “up” there.
The earlier, now-abandoned Geron trial to treat SCI was aimed at acute patients, that is: very close to the accident in time. We will be conducting such a trial later this year in Seoul Korea, but I would like to focus on this chronic paralysis trial today. There are several important points to consider to fully understand the impact of this trial.
First, the approval by the FDA itself. I believe it shows a growing comfort level with our spinal cord cells and our surgical route of administration. We will be using the same NSI-566 spinal cord product that we have been using in the now complete ALS phase one trial. In many respects those ALS patients are more fragile than the patients we will be treating in this trial. And after 18 surgeries, there were no SAE’s (serious adverse events) related to either the cells or the surgery.
We also showed compelling evidence in the ALS trial that the cells we transplanted survived for the life of the patients, regardless of the length of time the patients were on special drugs to suppress their immune systems. We have always thought that only transient immune suppression would be required for our cells to optimize their survival. This is important because these are powerful drugs and often the side effects from these drugs can be worse than the ailments they are meant to cure. The FDA is allowing a transient (3 months as tolerated) regiment here acknowledging comfort again with what has been demonstrated in the ALS trial.
Next, I would like to talk about how we think our cells can help these patients. A helpful analogy for me is to think of the spinal cord as a pipe that comes down from the brain through the spine. And inside that pipe are countless wires transmitting the signal from the brain through the spinal cord, which then innervates our body. When there is a “break” in that connection, when all the wires are severed, no signal can get through and all motor and sensory function below the point of the break is lost. These patients are referred to as “complete” as opposed to partial. These are the patients with whom we are starting.
In the ALS patients, even though our cells are integrating and synaptically connecting to host cells, there is no “break” in any circuitry descending from the brain. The benefit to the patients is provided by the nutrients that our cells pump into the areas of transplantation, which nurture and protect the remaining motor neurons and nurse some sick cells back to health. In chronic SCI, we are actually trying to “bridge the gap” with new circuitry provided by our cells. This will be the world’s first such trial.
The previous abandoned trial by Geron worked under a different theory. Again, thinking about wires coming down through the pipe, Geron’s theory was that “all” the wires weren’t really broken. They believed that some were left intact, but that the myelin (like the rubber coating on an electrical wire) was knocked off, no longer allowing smooth transmission of the signal through the wire. There has never been a consensus that in fact this is the case, but never the less Geron believed it and proceeded based on that belief. The company stated publicly that it thought it was too “hard” to rewire, or bridge the gap with new neurons. The cells they put in were meant to try to remyelinate those (hopefully present) remaining wires and restore the signal below the injury. There is also a trial currently ongoing in Switzerland attempting remyelination as a mechanism of action to treat these patients with different cells.
We do not believe it is “too hard,” and our goal here is in fact to “bridge the gap” with new circuitry. A recent peer-review publication this past fall reported exactly that outcome in an animal model of spinal cord injury using our cells. This data combined with the data from our successful ALS Phase I, is the basis for our belief that we can help these patients.
Again, as the FDA gets more comfortable with our technology, the trial designs become more streamlined. With four sites operating, and reduced wait times between surgeries, we believe that we can complete the surgeries and the 6 months data collection periods all within one year.
Of course, also as with the ALS trial, we are required to start with a small dose in the first trial with optimal larger doses reserved for later trials. But people thought we would never see a therapeutic effect in the ALS trial with the initial dose, and we believe we clearly have. So I am hopeful here too. We now know from the ALS trial that the cells survive and do what we expected them to do, long term, in the patients. It is a question now of optimizing the dosage and placement and doing large enough trials to statistically power a conclusion about efficacy. I believe spinal cord injury will prove out the same way. The cells will do their jobs. It is a question of how many, where, and finding out just how much we can help the patients.
When I met Christopher Reeves, he walked up to me, stuck his hand out and introduced himself and said “I’m famished, let’s eat.” I never met him again, before or after his accident. From what I have read about him though, he attacked all life that way, head on with no pretense, even after his accident. As Mr. Freeman’s poignant quote highlights, he was an inspiration to many people, and I can’t help but think he would approve of the way we are attacking SCI.
Blog originally published on neuralstem.com
Forward Looking Statements
This blog may contain forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements in this blog regarding potential applications of Neuralstem's technologies constitute forward-looking statements that involve risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Neuralstem's periodic reports, including the annual report on Form 10-K for the year ended December 31, 2012 and the Form 10-Q for the period ended June 30, 2013.