Can We Restore Mobility to Spinal Injury Patients?

Transcript

ERIC: There are over 30 miles of nerves in the human body carrying electrical signals from our brains to every muscle and organ. An injury to the spinal cord can prevent many of those signals from being received.

Today on Pulsar, we will hear about an extremely promising treatment that can restore the body's ability to carry those signals.

I'm your host, Eric. Thanks to Facebook Boston for supporting this episode of Pulsar.

Joining me today is Dr. Parag Gad, a neurobiologist and assistant project scientist at the University of California, Los Angeles. Dr. Gad, thank you for coming on the podcast.

PARAG: Thank you for having me.

ERIC: So let's start at the beginning. How does an injury to the spine affect mobility and a person's ability to walk?

PARAG: So the basic dogma that exists is that walking is a phenomena of the brain. That's actually incorrect. The brain gives you the command for go, no-go. But the actual processing and how to make that happen - how do you actually walk? - that's controlled by the spinal cord.

And for a matter of fact it's not just walking, but all forms of movement. When you are moving your hands, when you're talking, trying to drive, all of that is actually controlled by the spinal cord and, to a very large extent, is in some sense automatic. And it's controlled by peripheral sensory information.

The best example you could consider it is when you're driving from work to home or home to work. You would be able to drive through all of that without even realizing that you completed the drive.

You'd be on the phone, talking to people, listening to music, or looking at the surroundings, looking at whether you'd make a turn and you'd think, oh my God, I just made the turn. And immediately realizing because your system is really built in to make that automatic movement occur.

The same with walking. When you're walking on a treadmill, walking over ground, you can walk without thinking about other things. That's because your spinal cord is what is really controlling and driving the movement. The brain just gives you the command "go" or "no go."

ERIC: So the spinal cord takes the commands originating in the brain and turns those into action.

PARAG: Action, exactly. So after a spinal cord injury, what happens is an individual is paralyzed but the circuitry that's controlling the movement was considered to be dead.

But that's not the case. It's only dormant. It's lost communication with the brain. And because they have lost communication, it's unable to process the information to generate the required output because it can't sense what's happening down there.

That's one of the reasons why an individual with a spinal cord injury that causes paralysis is unable to walk.

ERIC: When we think about the term "mobility," we tend to think of walking, but your research is also looking to restore other functions. So what other systems in the body can be affected by a spinal cord injury?

PARAG: The inability to walk is just the tip of the iceberg. A person with a spinal cord injury basically loses almost every function. They lose the ability to sense, so they can't sense what's below the injury. They lose the ability to stand, of course, along with walking.

Along with that you have loss in autonomic function including bladder-bowel dysfunction, sexual dysfunction, cardiovascular function may be impacted.

You may have lost an ability to cough, ability to breathe appropriately, depending on where along the spinal cord injury occurs. So pretty much all bodily functions are impacted one way or the other with the spinal cord injury.

ERIC: Your research has led to some amazing results. So can you give us a big picture overview of your goals when working with patients who have spinal cord injuries?

PARAG: So our basic principle is that we can electrically deactivate and retrain these circuits that are intrinsically controlling these bodily functions - be it locomotion, be it bladder-bowel, be it sexual function, coughing, breathing, all of them.

And we do this by sending low-intensity electrical pulses into the spinal cord by placing electrodes noninvasively, such a non-surgical approach, or the back of specific regions.

And by sending these low-intensity electrical pulses we can activate the circuits in the spinal cord that are responsible for controlling these functions. We can allow re-communication with the brain to occur.

The way I describe it is it's a hearing aid in combination with a spinal pacemaker. So the spinal pacemaker provides this constant tone that generates the rhythm required to keep an organ going.

Along with that it acts as a hearing aid bidirectionally. So the brain can hear what the periphery is trying to say and the benefit of the muscles can feel what the brain wants it to do.

ERIC: That's amazing that a non-invasive technique can have these results. When we asked for questions on restoring mobility mostly we heard people asking how you could physically reconnect such delicate and small features in the human body.

So instead I'll ask, how can you possibly achieve this result using only electrical signals originating outside of the body?

PARAG: That's what took us years to figure out as to how can we stimulate noninvasively without causing any pain or discomfort to the individual, also have sufficient level of excitability that can actually hit the spinal cord and have a positive impact, and have sufficient level of selectivity.

That when you're targeting organ A, it has a high level of efficacy for that organ need. That's basically what took us years to identify - what the bottom-most stimulation needs to be.

The other advantage of doing it noninvasively is, apart from the simplicity and the cost factor, it's the ability for us to stimulate along the length of the cord.

With an implantable system you can only target one region of the spinal cord. But for using our non-invasive approach you can move the electrode up and down the spine as needed.

So if you're looking at the hand malfunction, you would stimulate up in the neck area. If you need lower extremity function or bladder-bowel function you would stimulate down in the lower back area.

Having this flexibility and the ability to move up and down really is a game-changer as compared to the implantable system.

ERIC: And we did get a question from Will, who asked how long this treatment takes to show results.

PARAG: The results are almost immediate, which is surprising to believe but that's the reality. We worked with about 70 patients so far, ranging from different kinds of injuries and years post-injury. As early as six months post-injury to as late as about 34 years post-injury.

And pretty much all the responses across the spectrum have been relatively the same. So it really doesn't depend on how far out you are post-injury, but it depends on how well you've maintained yourself.

ERIC: Well it's amazing that the circuitry could still be used that long after an injury. Can you give some examples of some of the results that you've been able to achieve?

PARAG: If you're stimulating up in the cervical area we're able to improve hand and arm function. And the classic example here is that an individual that's lost hand and arm function will able to restore the ability to open sealed bottles of water and flip pants from a hanger.

They were able to open fortune cookies. All of these would probably seem trivial in our day-to-day lives but for an individual that lost these functions, they're a huge change in quality of life.

The ability to actually open a door knob on your own and not have to depend on someone else do it for you - that's a game-changer.

Similarly, looking at the lower extremity function, we able to restore independent standing in almost all the individuals we worked with.

Within one or two sessions of therapy we've been able to restore over-ground locomotion to some extent.

With some level of assistance we've restored the ability to empty the bladder and improve sensation of a full bladder, reduce the number of incontinence episodes in some of these patients, and some anecdotal evidence of improvement in bowel function.

Where normally they would take about one to two hours to complete a bowel program, which is 10% of the day - that we could be able to bring down to less than 20 to 30 minutes, which is obviously a huge change.

As well as some anecdotal evidence of improvement in sexual function in males especially. All of these are observed within one or two sessions of turning on the device but they continue to improve as a patient receives therapy.

ERIC: You mentioned a few factors that determine the effectiveness of the treatment. What about the type or extent of a spinal injury?

PARAG: The severity of the injury makes a difference where a person that's more severely injured may respond to a smaller extent. The recovery may be slower and lesser. Someone that begins with a high level functionality - the improvement is greater.

ERIC: We also got questions about the complexity of the spinal cord and its pathways and connections. Does that result in your equipment being very complex as well?

PARAG: As a matter of fact, the system is actually very simple. What we capitalize on is the smartness of the spinal cord. The spinal cord is a lot smarter than what we imagine it to be. And what we do is we tap into this smartness.

And we don't actually have to induce any activity or muscles to be contracted in a certain way.

By tapping into this automatic nature of the spinal cord we are able to allow the spinal cord to determine what needs to be activated and by how much. There are millions of neurons in the spinal cord.

We don't have to electrically activate one over the other or in a certain pattern to generate a movement. We provided a certain level of excitation and tell the spinal cord, OK, your baseline has now gone from point A to point B.

And based on what the brain is trying to say and what the benefit is trying to say, you are able to make that movement.

If you take an example - the analogy of a car. If there's enough gas that you're pushing, the wheels will start moving. And if there's a slippery road it'll respond to that or if there's a rough road then we coast in response to that.

This is the same system here, where the engine is the spinal cord. And we're providing it enough energy and allow it to run based on what the brain - which is the steering wheel - asks it to do.

ERIC: So rather than thinking of a spinal cord injury as a severing of the communication lines between brain and muscles, really we should be thinking about it in terms of an altered or partial connection that can be trained to still carry a signal.

PARAG: Exactly. And about 97% of injuries that are considered complete are actually anatomically incomplete. And there are some spare fibers that are still communicating through the site of the injury.

The analogy of the hearing aid - we're able to capitalize on those spare fibers and say, whatever minimal communication that's occurring can be amplified with signals.

And just by amplifying that bi-directional communication and by activating the local circuits that are controlling these functions. Without having to activate them one at a time, but a more global level of activation, we get the response that we are intending.

ERIC: Well it sounds like you've had some really promising progress so far. Is the hope that one day we'll be able to restore nearly full motor function to many paralyzed patients?

PARAG: That is the target. That's what we are working towards. We don't want to limit traditional motor function.

Our whole principle is that we want to treat the body as a whole, treat pretty much all the end organs that are impacted due to the paralysis including breathing, coughing, bladder-bowel, sexual function, locomotion, hand and arm sensation - all of it.

The Holy Grail is to get to the organism as a whole, including organ locomotion independently.

ERIC: Finally, what is the status of this research now and what are you hoping to accomplish in the near future?

PARAG: One big limitation that we have is resources and funds. That's what limits the amount of work that we can do. There are plenty of ideas that we have and we've already to show them to be successful.

Having the ability to really push this along is limited by the amount of resources that are made available to us.

The next big thing for us is to really push this out and test out each of these - not just individually, but as a combination - and see how each of these organs interact with one another.

And if an improvement in locomotion has an impact in bladder with an improvement in cardiovascular function, improved breathing, and every combination of that sort.

And not limit to just a few weeks of therapy that we've been able to do for the last few years because of resources, but see what can be done over a period of one year, two years, three years.

And have the device made available to patients at home so they could then stimulate themselves while they're doing activities of daily living and self-train. And see the improvement and not just limited to rehab in the lab environment at a clinical environment.

ERIC: Well Dr. Gad, Thanks so much for sharing your research with us. And good luck carrying it on in the future.

PARAG: Thank you, Eric. Thank you for having me. It's a pleasure.

ERIC: You can learn so much more about the human body at the Museum of Science by visiting the Hall of Human Life, Green Wing, Level Two.

Until next time, keep asking questions.

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