Daniel C Lu, MD, Associate Professor of Neurosurgery at UCLA, Neuroscientist and Neurosurgeon, talks about clinical trials involving patients with spinal cord injuries and how magnets may play a key role restoring some of their basic functions.
Interview conducted by Ivanhoe Broadcast News in November 2018.
Let talk a little bit about using magnets to cure a problem for people that has been going on for a long time?
Dr. Lu: Right, the basis of this research comes from the fact that we have two observations. One is in the traumatic survival setting where the spinal cord is injured, the injury is often times not a complete injury and consequently means that there are residual pathways still connected past the spine injury point. The other observation is that the spinal cord is actually a very smart organ that processes information and has retained memory and things like that. Those two observations combined together allow us to have normal strategies to improve function after a spinal cord injury. The stimuli that we use are actually off the shelf for treatment of depression for the brain function and we actually use it to modulate the spinal cord circuits to enable function after a spinal cord injury.
How exactly does it work?
Dr. Lu: There are potentially a couple of theories of how it is working. Because the injury is incomplete there is still signal from the brain down to the spinal cord past the location of injury. That signal is weakened or attenuated in the injured setting. What the magnet or this electrical energy does is that it modifies the signal in such a way that it becomes functional, the neurons and circuits at the spinal cord level can interpret that as usable signal and can restore normal function again.
You and your team thought because it’s a magnet it might restimulate everything? Was it logical thinking or was it kind of out of the box ballpark, let’s try a magnet?
Dr. Lu: That came out in a different manner. We’ve done a lot of implantations so I had a neurosurgeon implant stimulators into the spinal cord to treat pain and there’s been a long history of that. These epidural stimulators or these similar to that are placed on a specific location; just on top of the spinal cord, called epidural space. That stimulator actually blocks signal from being received by the brain that’s interpreted as pain. So that’s to treat chronic pain conditions and that device has long been FDA approved. Our use of that device, an implantable device, is to treat in the setting of spinal cord injury settings, to re-enable function and to modify an injured circuit in such a way that it becomes functional again. That requires surgery and it’s invasive, it requires implantation of a battery and in patients who are spinal cord injured they are rather fragile patients, they’re not really good patients for these implantations to occur. So we look at different novel methods of stimulating a small cord without actually doing a surgery, and one of which is actually using the magnet. The magnet is actually noninvasive and people use it to modulate the signals in the brain to treat depression. And if that can happen then logically, potentially, we can apply that to the spinal cord and to modulate the circuits within the spinal cord so that we can have improved function after injury.
Tell me a little bit about the procedure, it’s not very long, it doesn’t take very long?
Dr. Lu: No that’s actually what’s fascinating to us, is that it takes only about twelve minutes of stimulation. We place this magnet on the back of the patient, the location has to be somewhat specific to target the location for in this case bladder function. Twelve minutes twice a week we treat this. And subsequently over the course of about four weeks you can start seeing improvement. It’s not immediate improvement, and the improvement is in bladder function in this case, but improvement is actually sustained. So it’s not that we actually need to stimulate in order to make the patient go to the bathroom or urinate. In this case they actually can go normally as they would normally do before they were injured. The patient in order to urinate does not require the stimulation to be actively on, and the procedure is only when they are in the clinic we stimulate for twelve minutes twice a week. And they can go home and conduct their normal business and they are also able to go to a bathroom and urinate on their own.
Is it forever twice a week or is there a maintenance program once it starts to work?
Dr. Lu: Yeah and this is where the research is going is that what is the dose that we need to stimulate in order to have this sustained activity in terms of bladder function. The period of time that once we get them to be able to urinate, that activity is sustained for about four weeks. And then they have kao effect and they have to be restimulated in order to have that sustained improvement. It’s actually quite interesting. The scientific question would be why is this occurring, why is there a memory effect. This is not something that we necessarily see with other types of simulation like the implantable epidural stimulation There’s differences in those type of energy. One’s electrical the other is magnetic, and there may be some durable effects from magnetic stimulation that is not observed in the electrical. And that’s where our science, our laboratory is actively investigating why that is.
When you discovered this works after four treatments, that was part of the clinical trial?
Dr. Lu: That was part of the clinical trial.
And is that part over?
Dr. Lu: That study has concluded. That was part of the Department of Defense funded trial. We’re actually at the end of this trial doing a more involved study in terms of asking those exact questions. What are the doses necessary to stimulate in order to get the effect, what’s the timing of stimulation to maintain those effects, and whether this is applicable to all patients.
What were the study results, did it work for everybody?
Dr. Lu: It didn’t work for everyone and I think this trial was blinded and shamed which means that we’re masked, we’re shamed means that the investigators, me included, we don’t know what energy we’re actually giving the patient and we actually have a sham stimulation; where the device then coils exactly the same as the real thing but the energy delivered is actually not adequate for therapeutic effect. So that study was both blinded and shamed. The subsequent study will be in that setting, but in broader patient population. The previous study was only five patients; we’re actually expanding this to a much larger population and also including both female and male patients. Previously it was only male patients.
So how many of the five did it work for?
Dr. Lu: Of the five, two actually were completely off of catheterization. Catheterization is the normal treatment for these patients who have bladder dysfunction after spinal cord injury. Catheterization involves inserting a catheter through a urethra and manually evacuating the urine and bladder at a set interval period of time. That as you can imagine is not only disruptive to their daily active functioning and living but it also introduces a potential for infection. And infection in this patient population is a problem because it can cause sepsis, kidney failure, and so on and so forth. Reducing catheterization can help to reduce not only the frequency of which it actually will impact their life substantially so practically and also decreases the risk of infection. So in two out of the five patients they were completely off of catheterization during this time, they actually had improved function. Two out of the other five had substantial decrease in function. Then there’s one out of the five that has improvement in function and also a decrease in catheterization frequency but less response to the treatment than the others.
So the study is going to include men and women, how big will it be and when does that start?
Dr. Lu: We’re currently conducting that trial right now. That’s probably triple the size of the current study, about fifteen patients including men and women. And we’re actually looking at what is the frequency of stimulation that’s necessary to induce the function and what’s the longevity. As well as why is it that certain patients respond to this and certain patients don’t. So we’re looking at their injured characteristics, the chronicity of injury, how long ago was the injury, different characteristics of that.
Are you still accepting people to that trial?
Dr. Lu: Yes we are.
I can’t imagine living with a catheter for the rest of my life it’s got to be so much hope for these people.
Dr. Lu: Absolutely and one thing that you and I may not know, I certainly didn’t know when I was approaching this problem, is that if you ask a lot of patients with spinal cord injury what function would you want to address first in terms of spinal cord injury … It can affect their motor function if they have thoracic injury, they can’t move their legs, it can affect their temperature regulation, their bowel and bladder function, sexual function as well a whole host of these functions … If you ask them what of those functions do you want to have back the majority of them would rank bladder function in the top. One of my patients actually told me this, he actually relayed this to me as to why. He’s a thirty year old guy, hangs out with friends, and is still very active. He says yeah, when I go out for a beer with my friends I sometimes can’t do that because it depends on when they drink and on what the restroom set up is like, they sometimes don’t have access to restrooms. They have to catheterize themselves according to how much they drink and how much they intake. Can you imagine we don’t think of this at all sometimes? We drink and sometimes we’re a little bit inebriated and we lose track of when we need to go to the bathroom or not. But in these patients when the bladder fills up there’s a condition called autonomic dysreflexia that can occur. It could be because their blood pressure can rise really high and they can be tachycardic meaning their heart rates can be really high. They can be flushed, they get a headache, and subsequently because of that it can be a life-threatening emergency for some of them. When that happens, when their bladder fills up, if they lose track of time and they’re at a bar or pub hanging out with their friends and that occurs it’s a problem for them. So sometimes they don’t even go out anymore. Much less a lot of times they have to look at the setup of the bathroom, if it was handicap accessible, whether they have a catheter with them, whether their cervical injury if they access it and can’t use their hands they would need to catheterize themselves, sometimes they won’t have that ability to catheterize themselves they need to have a caregiver. As a result of that, because of these simple things that you and I take for granted of not being able to urinate they don’t go out. They’re estranged from their friends, they don’t have access to that social network and it’s a problem. This has a potential to address that and that makes a meaningful impact on their quality of life and ability to interact with friends and engage and still provide enjoyment in life.
The patient that’s coming in did it work, is he one of the two or is he in the study now?
Dr. Lu: He’s currently in the study right now. You’ll find him very, very interesting. He has a medical background; he’s actually going to medical school right now. He can articulate a lot of these issues with you in a relevant manner. He’s going to school right now, a very accomplished young gentleman, and he’s currently enrolled in the trial.
Is it working for him yet?
Dr. Lu: I can’t say because it’s blinded.
What haven’t I asked you about this study or the discovery that you would like us to include in the story?
Dr. Lu: There are a lot of things that are happening in the realm of spinal cord injury. Not just from my laboratory at UCLA but from a lot of other people around the nation and the world; it’s a very promising time right now. And certainly to the patients who are suffering with spinal cord injury or living with spinal cord injury there are a lot of novel treatments that are up and coming in the next five years. That would be very, very highly optimistic.
END OF INTERVIEW
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