Dr. Michael McIntosh, a scientist at University of Utah Health, is working to isolate pain-killing compounds that could serve as a non-addictive replacement for opioids. In this episode, Dr. McIntosh talks about what his early research has found, how these venoms work and the major changes it could make in the way doctors treat pain.">

Apr 19, 2017 — An aquatic snail from the Caribbean Sea could hold the secret to a new type of pain killer in its venom. Dr. Michael McIntosh, a scientist at University of Utah Health, is working to isolate pain-killing compounds that could serve as a non-addictive replacement for opioids. In this episode, Dr. McIntosh talks about what his early research has found, how these venoms work and the major changes it could make in the way doctors treat pain.

Interview

Interviewer: Snail venom as a possible alternative to opioid-based painkillers, that's next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. "The Science and Research Show" is on The Scope.

Interviewer: Psychiatrist Michael McIntosh is involved in research that's exploring using venom from a small cone snail, which is common in the Caribbean Sea to treat chronic pain. And in this study, the researchers found that a compound isolated from the snail's venom acts on a pain pathway, which is different than the pathway targeted by opioid drugs. Thank you for joining me today. And the first question I have is to explain pain pathways because I think that's going to be an important part of this conversation.

Dr. McIntosh: Pain pathways involve sending the signal from the site of injury, you crushed your finger, processing it up through nerves through a place called the dorsal root ganglia into the spinal cord and up into the brain where we actually sense the pain.

Interviewer: Okay. And how many pain pathways do we have? Do we even know the answer to that question?

Dr. McIntosh: I don't think we know the answer.

Interviewer: Yeah. How many do we know of?

Dr. McIntosh: All the transmissions to sense pain go up through that back part of the spinal cord. But the types of pain and sensations that we can feel come from a variety of different receptors that can experience cold or heat or noxious pain, itch.

Interviewer: The pain that opioids help prevent is a very specific type of pain pathway and you discovered a different type of pain pathway that the snail venom actually affects. Explain that a little bit for me.

Dr. McIntosh: Opioids are outstanding medications for treating acute pain, pain that occurs in the short run. What's more difficult is to treat long standing or chronic pain and in particular, pain that comes from injury to a nerve or neuropathic pain. What these compounds from the snail do is they not only provide relief in the short run, they seem to provide long lasting relief and they seem to do so by actually preventing some of the pathophysiology that occurs after a nerve injury.

Interviewer: So it isn't so much the pain pathway is different, it's how the substance is acting because from what I understand, the body gets rid of the substance within four hours or so, but the pain relief of the snail venom lasts longer than that. Why do you think that is?

Dr. McIntosh: We think that's evidence that there is a rescue mechanism going on, some disease-modifying effect. The data indicate that after a nerve injury, you actually lose nerve fibers, you lose the insulating sheath around the nerves, but if you give this compound, it decreases the loss of nerve fibers, spare some of that loss of myelin and we think those changes then translate into longer lasting pain relief because there's less ongoing injury.

Interviewer: So what came first in this research? Was it the interest that it was a different pathway that this affected or was it . . . and then you discovered the side effect after the fact?

Dr. McIntosh: Really, basic research, our primary interest has been on the components in the venom themselves because they make outstanding tools for studying the nervous system. But there was an observation after injection of this compound that the animal seemed to experience less pain so we began investigating after that.

Interviewer: So you just kind of followed that lead . . .

Dr. McIntosh: Absolutely.

Interviewer: . . . that was presented. And then it's fascinating to me because you discovered that it seemed to lessen the pain but then you have to prove that or show how. I mean, you have to go through a lot of work to get to the end point. Explain some of that process.

Dr. McIntosh: We do. The things generally begin with animal studies and that's helpful. There was a related compound that reached human clinical trials and then the discovery was made that the compound was less effective on humans than it was on the animals because it was less potent on the responsible receptor. Part of our recent research has been to re-engineer the snail peptide into something that is effective not only in animals so you can conduct the animal studies, but also in humans.

Interviewer: And then the delivery is a little tricky too, isn't it?

Dr. McIntosh: Delivery is tricky because it's a small protein known as a peptide. If you swallowed it, your gastric enzymes would just digest it. So in this case, we delivered by what's called a subcutaneous injection much like diabetics use to inject insulin.

Interviewer: And, originally, what made you decide that looking at any sort of animal venom was a good place to start for any sort of research for medicine? That seems very counter-intuitive to me.

Dr. McIntosh: Each species, and there are hundreds of them, has hundreds of unique components in their venom. So there are literally tens of thousands of unique components which are designed to capture prey and, therefore, design to work on the nervous systems. o we felt that this would be a preselected library of compounds designed to act on the nervous system.

Interviewer: Yeah, why create them on your own when nature has created them and then you can see, well, what do they do?

Dr. McIntosh: Exactly.

Interviewer: And then you make adjustments from that point, if I understand correctly.

Dr. McIntosh: That's right.

Interviewer: So the latest bit of research that you did proved what, exactly? Because, I mean, this is a whole series of steps.

Dr. McIntosh: It proved two things. First, that we could take the compound evolved by the cone snails and turn it into a compound that's potentially useful with humans. Secondly, what we showed is that it could be used as a specific called chemotherapy-induced neuropathic pain. In short, what that means is people who get chemotherapy, say for a colon cancer, experience side effects that include damage to their nerves. This often limits the duration or amount of the compound that can be given and it's quite painful and uncomfortable for the patients. What we found, in this case, was that we could give the chemotherapy agent and our compound that we developed and prevent the nerve damage that normally occurs after the chemotherapy.

Interviewer: And what's next step for you with snails, venoms, and pain?

Dr. McIntosh: The next step is to conduct additional preclinical trials with the aim of applying to the Food and Drug Administration for investigational new drug status so that human clinical trials can begin.

Interviewer: And then beyond the chemotherapy, will there be other applications?

Dr. McIntosh: We think so. This appears to be a more general mechanism, so there is a variety of ways that nerves become injured. It can be through a disease process like diabetes and many diabetics have painful neuropathies. It can be through injury, a surgery, car accident, low back pain, things that cause injury to a nerve and the pain becomes chronic.

Interviewer: And I think I may have misled our listeners in the beginning of this interview because I didn't quite fully understand. But what makes this compound, and I think I've said this, but it bears worth repeating, what makes this compound really useful is it not only blocks some of the pain pathways but it also affects the nerve health and helps regenerate them so then the pain will no longer be there for the patient, hopefully.

Dr. McIntosh: That's correct.

Interviewer: That's pretty exciting, isn't it?

Dr. McIntosh: Yeah, that is very exciting. Because we want to get at the root of the problem, not just mask the symptoms.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.


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