It was all based on decades of work from multiple labs, not just ours. One of the most important set of experiments were done in Moscow in the 60s and 70s. They put an electrode into the brains of animals and gave it just a tonic dose of juice. And then on treadmills the animals began to step . . . these were animals that had had their cerebral cortexes removed.
How important is location? All the variables are important. Realize that what we’ve seen so far is just the opening of a door. We’re at the model T stage in terms of the technology, and we know it can be much better.
So far we haven’t been able to get complete, full weight-bearing independent stepping in our subjects. Fine tuning the technology is going to be important . . . there are an infinite number of variables to control, and remember that we’ve spent a year with our subjects. The Cal Tech engineers are going to be what makes this possible for more and more people.
People don’t realize how significant this neuromodulation is.
Conversation about the wrongness of telling people they can’t move. Forget it! It’s just a false message — and yet you’re not going to get voluntary control without making an effort. The fact that our four subjects could perform movement based on sound and images means that their brains have re-wired themselves.
Gregoire Courtine used Swiss chocolate to get his rats to desire walking — it was his way of creating “voluntary” response.
Question about changing the shape and size of the electrode array. We don’t have any idea what the best configuration is — this is a new technology. We have lots of animal experiments to do before we understand this. There are so many options that we have to be careful not to get carried away and put everything in there.
The Big Idea next 36 patients will be using the same electrode array that was used on the first four.
Question about autonomic responses. This was another happy surprise for us. We were pretty skeptical about even talking about it, but the guys were saying it was happening. All these physiological systems are highly coordinated. . . once you get a person standing, their physiology changes. It’s all connected. Your locomotion is connected to your bladder . . . there’s film of this rat and you can see his gait changing depending on whether he’s getting to pee or not. In rats you can stimulate on cue and get the rat to void.
Can this be shared with other practitioners so they can use this as an exercise methodology? I’m at a really frustrated state now because so many doors have opened and we want to see things done correctly and not too fast so that things don’t work. One thing that I really emphasize is that rehab is really important. You have to get insurance companies to recognize this.
What would the downside be for getting one of these stimulators put in? Reggie says, “do you know a good neurosurgeon?” Laughter, but really . . . aren’t lots of people thinking of having this done? What is the reason not to?
My thinking now is that the autonomic system might be low-hanging fruit.
We’ve studied 6 cervical patients with weak transcutaneous stim for a few weeks, then added a serotonergic type drug for a few weeks, and at each stage they’ve improved. We’ve also implanted to subjects epidurally. We wanted to know if we could stimulate the cervical cord just like we did the lumbar cord. People used to think that you had to have the central pattern generator, but that’s not true. We’re seeing the same kinds of results cervically. And we’re in the 2nd year of a 5 year program to understand that.
Question about the optimal strength of stimulation . . . depends on the individual, but we start just above the lowest threshold and then try to use the least possible stimulation. One scientist stimulated at 20% below threshold and then quantified the amount of movement of the rats in their cage, they were moving 5 times more than the rats without stimulation. We don’t want to induce the movements, we want to enable them.
Do you think we’ll be able to do this transcutaneous only? So that people don’t have to have epidural surgery? We think it will vary, and we think it will vary over time.
How should someone like me — who is ASIA D — think about this? People asked me why I wanted to start with completes, and I said offhandedly “because incompletes would be a piece of cake.”
My frustration was picked up on by NIH. Where do we go from here? There’s so many ways to go from here? I told them, you’d better pay attention to what’s happening here because if you don’t there will be a lot of angry patients. The director called me and asked, “What can we do?” I was so stunned I didn’t have a good answer. We’re having a workshop on November 15th. We have all this stuff do and all of it is going to cost a lot of money . . .where do we start? What’s our strategy? We’re getting together the NSF, multiple institutes from the NIH, SCI organizations, the US Army, DARPA . . . shouldn’t we have some strategic plan to address these problems?
What’s the anticipated timeline for FDA approval on the devices? Nick from NRT is leading our commercial effort. For the transcutaneous, once we get the resources we can do that in two years. For the epidural track, we think that’s a five-year deal. This is the first time we’ve been in a situation where we really think we know what to do.
One channel is: what can we do with the present technology? My team is focused on the next generation, not on what we can do with this. The Big Idea of 36 patients is going to be measuring all kinds of things, but while that’s ongoing we’re going to be looking ahead.
What I would like is for this to become a Manhattan Project. The smartest best people you could get were on it. That’s what we need to do. That takes a lot of money.
Are you financially constrained right now? We could start pretty rapidly with $5 million. Are you looking for philanthropic funds, partners? Crowd funding is a possibility . . . we’re going to get that started pretty soon. That’s for the development of the transcutaneous device.
Are there venture capitalists? No checks yet, but potential.
How can we get behind this?
Nick gets up. Nick Terrafranca, Neurorecovery Technologies. We started this effort about 4 years ago, moving this effort off campus. The first step was to pretect all the intellectual property. We have the rights for the exclusive development of this technology. The next step is really expensive.
Getting an implant to market costs $120 million.
Getting the transcutaneous to market can help offset the cost of the $120 million, so that’s what we’re trying to do. The transcutaneous itself is $5. That’s what we need. We need $2 million to development for the implantable, and another $70 to get it to market.
So about a year and a half ago we went out and started raising money. That put us into the business world, you land on show me the money. What’s the ROI. What’s the size of the market. We’re in the process of raising money, but there’s not much there for medical devices. What peopel are doing is putting money into social media. What scares them is the FDA pathway. We’ve slowly knocked down all these barriers.
We own the patents for both method and application. It’s a family of about 15 patents.
Are you working with others, like stroke, ALS, etc? We have experiments with other models, but no conclusive results right now. We actually think that the brain is interfering with the physiology of the cord.
What’s the diff between the device now used by the 4 guys and what you’re building? Sure. the new system will have a feedback loop so that you don’t have to constantly stop it and change parameters to use it.
The money . . . we’ve been in conversations with VCs, high net worth people, angel investors. Someone wants to know why these people are not forking over the dough.
Well, FDA. That will be slow, and investors don’t like slow. Implantable, nobody wants to touch it. Too long. They all say get to the clinical trials and then talk to us. We’re in what entrepreneurs call the valley of death. The next clinical milestone can be done in 8 months, and they want to wait for that before they commit.
Rob Summers is now doing 100 situps a day with weight on his shoulders . . . one of the guys who had a lot of spasticity learned to stand the quickest. But the effects of stimulation varies from subject to subject, and (a woman in the room is saying that) one of the guys has gotten worse spasticity when the stim is turned off. None of the guys take baclofen.
And we thank him for 40 years of work.
“Well, it’s been fun.”