Faith Brennan, PhD, a research scientist at The Ohio State University, talks about a new drug treatment for spinal cord injury patients.
I wanted to start by just asking you a little bit about what you and your colleagues are studying, just kind of an overview. What are you looking at in terms of helping people with spinal cord injuries? What other complications maybe they’re looking at? I’m looking for some background and context. And what are you looking at in terms of health and medicine?
BRENNAN: So, the spinal cord relays information between the brain and the body, and this is information that we don’t even think about in terms of things like blood pressure and heart rate. So when you have a spinal cord injury, this causes problems for the whole body. And this includes things like deregulated blood pressure, deregulated heart rate, loss of temperature control and systemic immune suppression. And these problems can predispose individuals living with spinal cord injuries to things like heart attack and stroke and infections, like pneumonia. And these health problems are the leading cause of morbidity and also early hospitalization and early death in this population. So, this is a very real problem that people living with spinal cord injuries face these health problems caused by deregulation of this autonomic nervous system, and that’s what we’re working on.
So, you’re looking at potentially repurposing a drug to help. Can you tell me what the drug is and what it’s used for now and what you’re hoping it does?
BRENNAN: So the drug that we’ve been using is called gabapentin, and gabapentin is widely prescribed for treatment of pain. And it’s often prescribed for people living with spinal cord injuries to treat neuropathic pain. This develops months or years after this spinal cord injury. And what our focus was was to test whether giving gabapentin early after the spinal cord injury rather than waiting until symptoms arise could actually prevent or mitigate these autonomic problems.
You are studying this drug in a mouse model, are you not? Can you tell me a little bit about that and what you and your colleagues are finding?
BRENNAN: So, we have been using a preclinical model of spinal cord injury in the lab to test whether giving gabapentin early improves outcomes in terms of these autonomic complications. And what we’ve found in this preclinical model is that, after spinal cord injury, there are structural changes that happen in the spinal cord itself below the lesion. And these structural changes actually promote all of these autonomic complications. And giving gabapentin early prevents these structural changes from happening and, as a result, we see reduced cardiovascular problems and also less immune suppression when spinal-injured animals are given gabapentin.
What would be the next step, Faith? Are you close to being able to move into human clinical trials. Can you give me some kind of timeframe and next steps?
BRENNAN: This is definitely a new way of using a commonly prescribed drug. The possibility of repurposing it for humans is very real because it is already used in spinal-cord-injured individuals for other indications – pain. And it’s – we still need to do more work in terms of understanding how long can we wait after the spinal cord injury before giving the drug that we still see the benefits. But we’re excited to continue this research and also potentially then move into human trials to understand the ideal window of administration. And it’s also very exciting because this is a very commonly prescribed drug, and the ability to use it for another indication could potentially reduce susceptibility to infections, help control blood pressure and heart rate in this at-risk population.
Are there any side effects from the gabapentin? Is there anything that people would have to watch out for down the road?
BRENNAN: There are some side effects that include things like headache, but this can actually be managed by adjusting the dose. Usually when it’s prescribed clinically, it’s increased in a stepwise manner. And then if side effects occur, it’s stepped back so that we can mitigate any side effects.
This is a drug that’s already approved for other use, you could move into human trials potentially without too much difficulty?
BRENNAN: We still need to understand, in the preclinical model, how long we can wait before administering the drug. This is an important parameter to study and understand before moving into clinical trials because the window of opportunity is very important in terms of who may be responsive to the drug in the clinic. So, we still need to do more preclinical work to understand that window of opportunity and then translate that to humans.
What’s the potential here, Faith, for people who are living with spinal cord injury?
BRENNAN: So the potential to administer a drug early in somebody with a high-level spinal cord injury and then prevent the development of autonomic problems like deregulated blood pressure and heart rate could significantly improve their quality of life. It could improve their independence in society, less caregiver reliance, less infections, hospitalizations, and potentially also improve survival outcomes.
You mentioned high-level spinal cord injury, is there a specific population of people with spinal cord injury for whom this might be a better fit?
BRENNAN: So individuals with high-level spinal cord injury are more susceptible to autonomic problems. Because of the way the nervous system is structured, most of the autonomic output would be deregulated the higher the injury is.
OK, and by high-level, is there a certain area and above which…
BRENNAN: Yes. So around spinal level T-six s is considered a high thoracic.
Do you know about how many people in the United that would be impacted?
BRENNAN: For those statistics there are different metrics used to measure. Some of the older statistics indicate there may be around 12,000 cases a year in North America. But this is not an exact science in terms of the demographics. It’s very difficult to model statistically.
And my last question for you, is there anything I didn’t ask you that you would want people to know about what you and your colleagues are doing in the lab?
BRENNAN: I think our research is really geared towards understanding what we can do now to help people living with spinal cord injuries and understanding problems that aren’t really thought about normally. So normally, when you think of paralysis, you think of loss of motor function. But there are all of these silent problems, and these include this blood pressure and heart rate, and a lot of people don’t think about that. So, our lab is really working to understand all of these silent problems to improve quality of life.
How can autonomic dysreflexia can be life-threatening, and so this can potentially impact that?
BRENNAN: So, when the blood pressure and heart rate become deregulated, this can become life-threatening when it can predispose individuals to a heart attack or stroke. And this can be very dangerous and be a medical emergency if it’s not managed and kept under control.
So, you’re still looking to see how soon after injury would be the prime time. How about dosage? Is there a matter of titrating dosage, whether you need more or whether you need less?
BRENNAN: The human dose of gabapentin varies widely. We used one dose in our study, a medium-range dose that’s a human equivalent in our preclinical model, and it would also be interesting to titrate the dose to understand how much we need to see benefits or when we lose benefits. We chose a human equivalent dose for this study that we worked on recently.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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