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.”
You might have to use a hook to get me off the stage here. That’s okay, I’mused to it
I am one of 8 owners of a comp
- understand the role of automaticity in sensory-motor interactions
- recognize how amplification provides a mechanism to re-engage those networks of automaticity
- understand how re-engagement of spinal networks enables re-learning more effectively via training
What we’re doing has been put in the category of miracles, but that’s absolutely the wrong word. There’s not any ONE thing that we should track and forget about everything else. For each patient, condition, person, one intervention might be better than another. We need to develop them all. If you call something that has evolved over a 40-year period a miracle, then okay.
About 7 or 8 years ago we got to a point where we realized that there was a real possibility of using the residual circuitry in the lower cord to take advantage of automaticity. We didn’t know how much we could get out of it . . . but we thought we might be ready to work with humans. Everything was pointing in the direction that the spinal cord of humans isn’t that different from that of all other species. It’s a project that’s hundreds of millions of years old. And because we’ve all evolved in a 1G environment, it makes sense that just getting up and standing and walking will have a major effect on multiple systems.
To relearn, there must be re-engagement of the circuits. This can be accomplished pharmacologically and via electrical neuromodulation when combined with training.
What we’re doing is changing the physiological state of the spinal cord. We want to make it more likely to engage the circuitry. We’ve been doing this with drugs and with various kinds of stimulation, including epidural, which has gotten a lot of attention lately. What a lot of people don’t know is that when you add drugs, the two things work synergistically together very well.
So what’s automaticity in movement? It’s not thinking about the details of the movement you want to make. Your brain is generally not engaged in directing your movements.
He’s got a spinalized rat up on the screen that was given a dose of strichnine. It couldn’t walk on the treadmill before the dose. It’s motoring along just fine afterward in this video. We started working with cats, and it took us five years to get this working in rats. Sorry it took so long, but that’s what happened.
The rat’s legs are getting no input from the rat’s brains. It can walk forwards and backwards and sideways. Oh my god, hilarious — they turn the rat harness sideways so we’re watching its legs do sidestepping while its face looks out at us. The weirdness of sci science, I swear to god.
Where’s the intelligence in the spinal cord? In the interneurons. He’s showing a set of videos of a guy with an intact cord lying on his side with some equipment attached to his legs and feet. The equipment provides stimulation of various kinds and measures what happens. He’s been told not to step, but there are certain inputs that make his legs “walk.”
So, they asked. Do we have enough information to get standing or stepping in a human with a complete injury? We had a meeting, we got funding. We had a hunch that it might work, but we didn’t know. We decided that the present technology would be good enough fro proof of principle. We implanted that technology into four young men, and all of them regained voluntary control.
All of them also got some return of autonomic functions like bowel, bladder, sex, temperature regulation.
What shocked us was the return of voluntary control. Our subjects #2,3 and 4 were motor and sensory complete chronics. According to our old theories, a damaged nerve was dead. These men should not have been able to move their feet and legs if that were true. There have to be surviving axons in order for this to happen. These men can even control their movements based on visual information — without any sensory input through their feet — they can look at a sine wave on a screen and time their movements to the rise and fall of the curve.
What’s going on? There’s some residual capacity, sort of hiding like a submarine under the surface. And the application of a specific amount of electrical stimulation will lift that submarine up above the surface where it can reach the level needed to cause functional return.
I’m goin’ to his breakout.
A couple of harsh realities.
Only 1 in 10 clinical trials is successful. Hardly any rat model therapies translate well into humans.
Sensory Input in the Injured Spinal Cord: Plasticity, Pain and Automonic Function, and Use in Neuromodulation of Motor Function
How many people in this room are in pain right now? Lots of hands go up.
Okay. After injury you have altered descending input and normal sensory input. You have changed integration inside the cord, which results in new motor or autonomic output.
Hmmm. In rats if you pinch the back of a rat, you get this weird skin shrinking thing. Showing this on a video of an anesthesized rat. Tweezers. Skin shrinks up all around the pinch.
It’s called the CTM intersegmental pain reflex. He’s going into technical detail about how this works, using a wiring diagram . . . eventually he’s going to circle back to how it relates to sci pain. Cross section of a cord showing big fat axons with lots of myelin and thinner ones with a lot less, and then abundant axons with no myelin at all.
Okay. Has anybody had to get medical care because they burned their thighs with a hot laptop? Half a dozen hands go up. So, pain is good, sometimes. But neuropathic pain is backwards, because lighter touch makes it happen instead of harder touch.
Why do we have pain above the injury level? Why do we have pain at all? Oh, people, this is a fail. He’s talking very fast, using a lot of jargon, and showing busy slide after busy slide, each one covered in data that I’m sure would be super helpful and informative if I could slow him down by about a factor of six. And he just said, oh, I need to speed up or I’ll run out of time.
He’s showing data that (I assume) explains why electrical stimulation works. It has to do with finding the right level of stimulation and the right sensory input. There are ways to use stimulation to decrease spasticity in motor incomplete type of injuries without taking away any voluntary motor control that the patient might have.
The work he’s discussing is about using sophisticated methods and measurements to home in on the exact quality of stimulation that benefits each individual patient. There could be a device that a person would get in, be assessed, and get a custom-designed stimulation program.
This talk is called The Hunt Continues: Novel Therapeutic Gene Targets for Spinal Cord Injury.
This is the conference I look forward to the most all year. The fact that this exists and that you’re all here means everything. And yet the goal is to kill it. Get rid of it. Let’s never have this conference again because we did it. (applause)
I’m at the other end of the spectrum from Wise. I’m doing basic science, and I’m not done until we have voluntary movement.
Reviews the problem: your axons grow out of the neurons in your brain, and so messages can’t get through. What can you do about? You can maximize function of cpinal circuits and any spared fibers below the injury site. You can improve the growth environment and get some connections made, which is what Jerry Silver was talking about. There are certain types of neurons in the brain, though, that just don’t respond to those kinds of strategies.
So my work is focused on those. There are 2 hurdles to clear to get this done. The cell has a giant metabolic task to get that long, long axon to grow. And it has to be madly organized.
But it can be done. We know this because fish can do it. The peripheral nerve system can do it. Embryonic state humans can do it.
DNA is the blueprint for protein production. Some regions of DNA are active, others silent. It’s hard to rebuild the axon protein by protein by protein . . . so we take a different tack. We focus on transcription factors, because they’re fundamental coordinating units that manage lots of proteins. This is what we focus on in our lab.
Transcription factors regulate DNA which produces proteins, which manage axon growth, which then find targets, which lead to functional recovery.
Down at the level of transcription factors there are genes that act like kill switches. They shut off the whole thing. So what if you find one? You put it into a virus and inject that virus into the brain of a rat and then you get axons growing. They have two genes identified: KLF7 and Sox11.
Does it benefit the animal? Does it get function? KLF7 does, a little. But with Sox11, we get worse outcomes than before we started.
We were very discouraged by that . . . but points at a key need in this field.
How do we monitor the functional output of regenerated fibers? it should be simple. You evoke activity in the fibers (and only those fibers) and then record responses in target cells. But how do you specifically evoke activity in a subset of axons? You use something called optogenetics, which involves putting a protein from algae into a neuron, and that makes the neuron light up when it fires.
So we did that. We can tell exactly which neurons are active and responding. If you have cells in the brain firing, you should see activity in the cord. And we do, in the healthy animals. When we looked at the Sox11 animal, what we saw is that there were synapses, but there were strange differences in the type and location of them. So now that we can measure it, we can improve it. So next we’re going to add some training and some chABC to see if we can get better results.
Okay, so what else are we doing? We’re trying to figure out how to get more axons to grow. And where do you find people studying lots of growth? In cancer research.
So he went and found all the transcription factors from cancer research. And there are 1400 of them, and it turns out that there are 12 factors that need to be studied.
This takes expensive equipment to pull off . . . and we have it thanks to Geoff Kent and his Spinal Cord Injury Sucks group, who rolled up one day with the money to pay for the microscope we needed.
One cool outcome from this is that we have been able to do high content screening to find new transcription factors, and some of them work. We’re looking at genes that nobody has ever studied, especially one called HHEX.
The support from private foundations (u2fp and scis) has allowed exploratory directions not otherwise possible. We would not be doing this work without you. No way.
Question: what are you going to do with HHEX? We think it’s an important inhibitor of axon growth, and we’re going straight into mice with it.
Question: why aren’t we focused in one location? Why are there people all over the place doing this work instead of being in one place, sharing their information instead of hiding from it? It’s a good question and speaks to the importance of collaboration . . . I obviously can’t answer the “why” . . . but there is some benefit to having things spread out. I’m at Marquette, and I do talk with people at sci centers, but I’ve also had benefit from people who aren’t working on sci . . .
Question: How can you measure living axon growth? Well, it’s an active area of research but right now we don’t have a good way.
Question about collaboration between people in chairs and scientists. Murray says that there should be a bottom-line collaboration requirement to funders. We should force the field in the direction of collaboration with the most powerful lever we have, which is the dollar.
I’m going to do something I have not done before. In the last few weeks I gave several talks, and I realize that some of the videos I showed were distracting the audience . . . they weren’t listening to what I was saying. So I’m going to talk for 20 minutes before I get to any slides.
I’m also doing something I haven’t done before. I’ve actually written up what I’m going to say, because I want to cover all the territory.
(Okay, I’m going to recap this as he goes, but I’ll get you the text itself if he’s wiling to share it.)
Most of history, no hope for repairing damaged cords.
Discussing some papers and history that are the background for his work in the China Clinical Trials . . lithium, lithium, lithium. Umbilical cord blood cells. They’ve done six trials.
1. 20 complete sci people given lithium
2. 40 subjects double-blinded to lithium or placebo . . . significantly reduced neuropathic pain in 5 out of 6 people treated. Unexpected result.
3. 60 subjects with severe neuropathic pain ( more than 5 out of 10) . . . have randomized 42 subjects from this trial. Half of them report significantly less pain, even 6 months after the trial has stopped. 18 more patients left to randomize and 6 months to evaluate them.
4. Transplanted 1.6 or 3.2 million HLA-matched umbilical cord blood cells, having spent 4 years developing a procedure to store and ship. They’ve seen no adverse effects. At one year, 2 of the patients had nerve fibers crossing the injury site. We don’t know if these are axon fiber bundles, but it’s hard to imagine what they are. Very disappointingly, none of the people who had these fibers growing had any motor return, though some did get sensory return.
5. At the end of 2011, beginning of 2012, we did 20 patients with chronic complete injuries – except one who was a c3 ASIA C. They got 1.6 or 3.2 or 6.4 million cells. Then we did a fourth group who got 6.4 million cells and a bolus of mp. And finally there was a fifth group that got all of that plus lithium.
6. 6.4 million cells into 13 subacute patients + lithium
Now talking about Kun Ming trial, which I think is #5 above. No study before this had ever shown recovery of walking . . . 3 of the subjects quit training partway into the study; they had fractures in their legs which were apparently there before the study. At 3-6 months, 75% of the patients were walking in rolling walkers with someone behind them with a rope to keep their knees from buckling. One patient was walking without help. When they went home, those who kept walking kept getting better.
Okay, I can’t keep up with all the data he’s reading . . . the gist is that there were people in these studies who regained walking. 10% of them could walk more than 100 meters without help. By one year 55% of the patients were no longer using catheters.
We don’t know what this is all about; we’ll have them back for a 2 year follow up.
The data seems to be all over the map . . . 17 subjects who got intensive motor training, and 15 of them recovered some walking.
Based on these results, we’ve proposed new trials around the world. They plan to sort people into groups that get one of five possible treatment menus. All will get locomotor training, no matter what else they get. The 5 menus are surgery only, surgery + lithium, surgery + lithium + cells, surgery + lithium + cells + MP, and um . . dang it.
But wait . . . we have people walking who seem not to have any voluntary motor scores. What? If you don’t have voluntary motor scores, how are you walking?
Why was the first study controversial? Because the idea that taking a couple of lithium pills could have an impact on the volume of cells was just weird. You’re not getting more cells, you’re getting cells with more dendritic trees.
What was the dose? The same dose that’s used to treat manic depression. It’s correlated with blood volume.
Has anybody ever gotten worse neuropathic pain from these studies? In the double-blind randomized study of 40 people, 2 of the placebo people got worse pain, and 2 of the lithium people got increased pain, but it was less than the 5-10 score.
Still HLA-matching? Yes, (goes into some technical detail about how this works)
Do the people who don’t cath have control? We estimate that half are using the crudet procedure, which is scrunching down and pressing on their bladders. I wondered if it had to do with the cost of catheters — nurses say no, it’s not that.
Describe walking with assistance. There’s someone behind using a rope to keep the person’s knees from buckling. They use a rolling walker for support.
Reggie says that they need to talk. I’d say.
A dozen people in the room . . .
What’s your road map to get to clinics . . .need FDA approval. To get there you need your devices to be safe. Probably they won’t approve the implants together at this point; the brain one is now being tested through a company called Cyberkinetics, but the investors rolled back. Now it’s being done out of Brown University, Ohio State. They’re using the blackrock system . . . c4 ASIA A spinal cord injury is the injury model. Have done 5 patients now.
Would do brain stem stroke patients as well, because symptoms are the same and there are about as many of those as there are sci patients. The whole package is extremely expensive.
What will the collaboration between stem cells and stimulating wires look like? They’ve been working on this but haven’t seen good results yet . . . also haven’t seen negative ones. They put 100,000 iPS cells in, sacrifice the animals after a month, then count how many cells survive. This is how they know that the cells survive.
Differences in inflammation with or without wires? . . . haven’t done that. All their animals get wires, but only some get stimulation through those wires.
Results of epidural stim stuff . . .is that informing your work? It has us very excited in thinking about an early human trial. We have a new neurosurgeon who is doing about 2 surgeries a month on people who have been losing sensory or motor loss to relieve bone compression on the cord that happens in people with longterm issues. They’re talking about adding the epistim device to the patients who are getting this surgery.
Seems very low risk and a case of “why not” since they’ll already be in there. We’re seeing this as the most exciting thing we’ve seen in the last five years.
The epistim model mechanism hasn’t been explained . . . lots of people are prepared to jump in.
Was there improvement from your stimulation in any area? We didn’t see improved pain sensation. We don’t have good animal measures for sensation improvement or proprioception. Anecdotally, we saw evidence that there may have been some improvement in both. There was also a marked reduction in flexor tone, like you see in FES cycling.
What’s the end game for the core research tracts?
I’m a basic scientist. We’re looking for partners, though, in the commercial medical device world.
How realistic is the wireless thing? I think that will happen very soon. We don’t have to develop our own technology because consumer electronics are doing it for us. The challenge is whether or not we can make it stable biologically.
But your electrodes look very small . . .
We have a grid that will cover a larger area of cortex . . . most likely a thin wire that works like the epilpsy stimulator. The issue is breaking the skin, which is how infections happen, but once you’re inside you can run wires safely all over the place.
What about the creepy factor? When you’re looking at somebody who’s chronic and complete you’re more likely to say yes, no matter how creepy it seems. It will be worth it to some people. This isn’t going to be something anybody wants to do during the first six months because they might be getting return during that time.
Question about proprioception. The answer is technical and has to do with setting up electrical fields instead of doing stimulation. He says that stimulation works better.
Another techy question that is going by me, sorry. It looks like a lot of the people in this room are AB folks who work in the field rather than people in chairs/caregivers.
With the pace of technology, it seems like the time lengths are getting really compressed . . . but how much time are we talking between today and when this gets to patients in the field.
What we know is that getting all the way through a clinical trial takes 5 years. From starting today. But we aren’t starting today. So, much longer. That’s where the 5-10 years comes from. BUT there are a lot of smart people working on the device/body interface, and there could be a breakthrough that changes that whole calculus.
What would you tell a patient to be doing to be a candidate? Our intervention is stimulation to restore movement. So patients will need muscles. That means FES. Maintain good health generally. Keep doing rehab. Don’t believe people who tell you that 6 months is a physical plateau . . . it may be a psychological plateau, a place where adjustments have been made, but there are people in this room for whom 6 months was not even close to being a physical plateau. Someone adds that range of motion is also important.
What about a brain/exoskeleton interface? it may not be technically that hard, but I don’t know anybody who has moved down that path.
Anything you didn’t get to? Okay, bladder and bowel. There are some opportunities from Big Pharma . . . they think they’ve tapped out pharmaceuticals, and they want to get involved in devices. In large populations, which isn’t us. For example, if we could develop something for mass consumers who have bladder issues — an implant in the peripheral system that could tell when the bladder is filling . . . you would wave a magnet over it and it would assist with voiding. It would be a small surgery, not terribly invasive. Would you be interested in that? Someone says that it’s more complicated than that . . . the muscles that control the bladder are not simple. So, if GSK wanted to spend millions on this, would people be interested?
Man says, my daughter would jump. She’s 21. She’s going to live another 50-60-70 years, and she would choose b and b over learning to walk in a second. Her network of young women with sci — all of them would say that. She was most interested in the return of b and b and sex from the epistim study.
Man says, he had a friend who lived sitting in pee for 10 years until she got a pacemaker thing. A spasming bladder has a mind of its own.
Well, GSK has set a very high bar. They want to put a cuff around the bladder that can sense the fullness, can stimulate the system JUST to void, and then can block activity if you need to. There’s currently a $1 million prize for figuring this out, along with a few others. Like blood pressure control, hypoxia, and bronchial constriction. You need to solve two of these. They’re giving out $200k to people who can demonstrate that they have a good idea. The $1 million would be for whoever solves it in the end.
It wouldn’t be working 2 walk without Jerry.
Talk is called Update on Experiments to Restore Function after Chronic SCI
Background . . . his Ramon Cajal drawing showing how axons die back after injury. Cajal thought the axons died. He was wrong. The axons are alive, they’re sitting in the white matter of the cord, waiting.
They’re trapped. Why?
Oh, and his cartoons that show the possible reasons. Not going to type this all out, because you can see it for yourself. Recommend going to watch this video from 2012, where you can see all of this introductory material yourself. It’s worth your time. Really. Or, if you have the 2012 book you can read the chapter about Jerry’s peptides and how they break down the environment that keeps axons from growing.
Still going over the peptide stuff, the first one of which was identified in his lab in 2009. These receptors are so interesting. It turns out that the receptors are like flypaper to axons . . . you get a bunch of them together and the axons can’t help themselves . . . they grow into it and never come out. What the peptides do is allow the axons to move through the injury site.
So they did their injuries to the rats. And in the acute rats, it worked very well. 21 out of 26 animals treated with the ISP peptide got some recovery. 3 of those recovered essentially fully.
They looked at what would happen if they increased the dose by a factor of 4 — and that made every single animal recover bladder function. When they looked at the slides, they saw that there wasn’t axon growth from the brain and past the injury, but there was a big jump in growth below the injury.
What about chronics? They damaged the rats. Then they waited for 2 months (which is a chronic phase for rats). Then they added chABC, and FGF (growth factor) and picked the scar, which he says is like cellophane, then they built a little bridge. And then they waited for 7 or 8 months.
They saw some kinds of nerve growth, but not all. Not serotonergic. Have not yet seen improvements in locomotion.
Okay, bummer. They need the serotonergic neurons. Why aren’t they growing? It looks like there’s a gene that needs to be turned off. It’s called SOCS3. So they turned it off and saw the peeing behavior improve quite a lot, but not the locomotion.
Gah, okay. Still need to mess with these poor rats all over again.
But maybe they don’t have to build a bridge at all . . . took a new group of injured rats. Waited 6 months. Injected ChABC, injected peptides. There were 10 animals at the start, but staying alive with injuries this severe is very difficult, and only 4 of them made it to the final part of the testing.
And one of those four was absolutely a superstar. (It’s hard to feel enthusiastic about rat recovery. It is.) And yet I can see that Jerry himself is feeling pretty enthusiastic . . . I mean he got a seriously damaged chronic animal to recover almost fully, and without needing to build bridges or rearrange genes.
They only did simple injections, remember.
Next . . . assemble a world class team to do combinations that will pull together what we know is working. Peptides, chABC, rehab, genes. That’s the agenda over the next few months.
One thing that occurs to me is that if it’s that difficult to keep chronic rats alive, we have a problem. We