Kip Ludwig, PhD in biomedical engineering and an associate professor of both biomedical engineering and the department of neurosurgery, talks about an injectable electrode for neurodegenerative diseases.
Interview conducted by Ivanhoe Broadcast News in October 2021.
Tell me about the injectrode, what exactly is that?
PROF LUDWIG: Have you heard of the cardiac pacemaker or deep brain stimulation? This is a device to kind of de-risk that surgical procedure where literally we take a syringe and we inject a deep nerve and we pull a metal conductor that forms in the body back out to the surface of the skin. So instead of having to implant a complex computer in the body that has to last 30 years, we actually make a connection from the surface of the skin to a deep nerve so we can talk to it with a non-invasive device. Similar to your phone or if people have used a tens unit for physical therapy, we can now start hijacking the nervous system from the surface of the skin.
What is the need that this is trying to address?
PROF LUDWIG: This is called neuromodulation. It actually is the fastest growing medical device market right now. There are over 1,000 clinical trials in it for diverse conditions such as hypertension, sleep apnea, obesity, Parkinson’s disease, essential tremor. It’s projected to be about a $23 billion a year market the next couple of years. And it’s this idea that sometimes drugs fail. Sometimes an orally administered drug, it gets into your body, it has to wax and wane, it gives your whole body a dose and things like that. If you hijack the nervous system, you can actually precisely tell the body to deliver its own drugs where you need it, when you need it for many different conditions. There’s been many FDA approvals in the last several years. The Inspire system for sleep apnea. I came from a company called CVRX to treat hypertension heart failure that just got FDA approval. You know, I worked at the National Institutes of Health, where there’ve been lots of drugs, but really no fundamentally new drugs in the lab in recent years. With these neurotechnology’s, there have been dozens of FDA approvals in the last five years, and they’re hitting the market right now.
With injectrode, is it working in collaboration with those devices?
PROF LUDWIG: Yeah, the idea is to get rid of the complex implant that’s essentially like taking your cell phone and sticking it in the body. And unfortunately, that is both very costly, but also has to last in the body for 30 years. How long does your cell phone last? If you just take a passive conductor and you route from the deep nerves to the surface, then you can take an external unit and talk to it. And that way it upgrades faster, the regulatory complications are much lower, the costs are much lower. Right now, these devices are only used when drugs fail, but if you get it to a simple system that’s, you know, $50 in cost of materials, that allows you to talk to the nervous system with a non-invasive unit, now you talk about being able to use this stuff before drugs. It takes the risk out.
For example, things like a pacemaker. Would that even remove the need for actually implanting a pacemaker?
PROF LUDWIG: Yeah. So that’s the sort of thing that we’re hoping for, is that all you would do is a simple injection under Lidocaine of really a metal wire bypass that talks to the nerve but comes back out to the surface. And it’s literally that simple. The hope is that by not having to implant the complex computer, you get rid of all the failure modes. You get rid of all the expensive costs, especially making sure it lasts in the body for 30 years.
What is injectrode made out of?
PROF LUDWIG: So the original variant was essentially like a surgical glue, where it was a two-part polymer that was liquid in a syringe and then when you inject it a nerve, it would cure around it and you could extrude it back out to the surface. Almost like if you use Play-Doh as a kid and used to put him through a spaghetti strainer, you can see the little things extrude out. It was like that. Now, it’s more like micro-embolism coils, where there are these little wire structures that can still be injected through a needle, but then form a wire to connect to the electrical circuitry outside the body. It’s certainly something that you inject that you can talk to the nervous system.
How can you see this being applied in a clinical setting?
PROF LUDWIG: So right now, we are developing it for a couple of therapies. One of the largest markets for neuromodulation right now is spinal cord stimulation for pain. There are many people with intractable back pain that’s so severe they can’t do their job. And right now we implant these kind of complex computer systems to stimulate the wires that are causing pain at their spinal cord, but they have a high rate of failure. This is essentially a stretchable polymer that’s a simple injection similar to getting an epidural during pregnancy or during delivering your baby. And it’s just a five-minute, under fluoroscopy, inject, pull up to the surface, and then you can talk to the spinal cord and kind of rewrite these pain signals. So right now, the spinal cord stem market is over a billion dollars a year.
How far away do you see this actually taking part in clinical trials?
PROF LUDWIG: There are already clinical trials. So, a company has spun out from this work called Neuronoff and you can go to clinicaltrials.gov right now. They have implanted their first 10 patients. Primarily, you start with small studies to show that the safety profile is similar to what it was on the bench in animal models and then you scale up to larger, more definitive clinical trials. But that’s really the hope of what we are doing here at the Wisconsin Institute for Translational Neural Engineering. This was a concept in 2017/18 and has already done human trials, and so we’re kind of hoping to accelerate the process to get the great research at Wisconsin from initial, early-stage studies to actually impacting human lives.
Is the first trial?
PROF LUDWIG: This is the first trial for the injectrode system.
How long has it been running, do you know?
PROF LUDWIG: These implants for about 30 days, the first cohort of 10, I believe. The very cool thing about the injectrode it is not only can you inject it minimally invasively, but you can also just pull at the tip of it near the skin and it unravels and removes very easily. So, these subjects were not only injected with it, but it was removed.
Have results come out yet from the trial?
PROF LUDWIG: So, it’s primarily a safety study, and we asses if it engaged with the nervous tissue. You start off with actually predominantly healthy subjects, so you’re not looking at it for the therapeutic purpose, you’re just looking at it as ‘is it safe to do and can it talk to the nervous system?’ It showed that it can talk to the nervous system for 30 days.
Going back to treating pain, you mentioned earlier on how this can even be applied before medication is used.
PROF LUDWIG: Yeah.
What can this do in the fight against the opioid epidemic?
PROF LUDWIG: Well so we actually have a grant specifically under the NIH HEAL initiative to look at device-based alternatives to opioids. And so that’s kind of the hope. Opioids really never treated the underlying pain, which is, to some extent, a dysfunctional wire sending an aberrant electrical signal. It just made you not care as much about the pain. Unfortunately, it was addictive. Here we’re actually going to the source, which are essentially wires sending signals you don’t want, and then we’re sticking in a wire and we’re rewriting those signals.
You have one clinical trial through right now, what’s the next step? Are there more clinical trials in the works?
PROF LUDWIG: Yeah. So, the hope is, in the next two years, there will be larger scale clinical trials where we look at efficacy for specific therapeutic indications. Because this is so minimally invasive, the hope is this will go through an FDA pathway called the 510K pathway and could potentially be approved for market in the next couple of years with just a single larger study.
Any side effects that have been seen so far with the 10 patients?
PROF LUDWIG: Not for any of the 10 patients that have been done. All of these implantable devices, if you’re putting something in the body, there’s a risk of infection, there’s a risk of damaging the nervous tissue or tissue on the way. But normally they’re doing much more invasive cut downs and things like that to implant these devices and computers next to them. This being kind of a simple injection. Our hope is that the risk profile is, you know, enormously lower than the existing devices used clinically.
Could there be any type of patient group that this wouldn’t be ideal for?
PROF LUDWIG: Well, there’s really two things. One is it’s a single wire system or maybe two to three that you inject. There are complex neural interfaces for things like the cochlear prosthetic that have many wires that talk to different nerves. It’s not really made for that. So, there are certain neuromodulation interfaces that it doesn’t allow the complexity for. It’s really just supposed to be very safe, very inexpensive, and very quick. The pacemaker right now costs $40,000 per implant. You know, this is, again, orders of magnitude less expensive yet more reliable and safer is our hope.
Anything I didn’t ask you that you feel that people should know?
PROF LUDWIG: Only that there’s more of this coming than you might think. There are deaf people hearing again, blind people seeing again because of implantable devices to hijack the nervous system. There are paralyzed patients who are walking again because of what we call broken wire diseases, where you can imagine, in a spinal cord injury, there’s a signal from your brain not getting to your body, and now we have the ability to implant wires to kind of do a neural bypass and connect the wire where it’s not broken past the break.
END OF INTERVIEW
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