Biomedical engineer at University of Central Florida, Melanie Coathup, PhD talks about a possible treatment for menopause symptoms.
Interview conducted by Ivanhoe Broadcast News in 2023.
So, the three big things women complain about in menopause are brittle bones, weight gain and heart pressures. This touches on the first two. That’s a big concern for women as they get older.
Coathup: Yeah. Well, with the brittle bones, that is a significant concern, and also the weight gain as well. And when we looked at our molecule, which is what we call pool 7, compound 3, or P7C3. It’s remarkably it helped to prevent the bone loss. It prevented the deterioration in bone quality, in bone structure and maintained strength to a healthy component. But the other was just fantastic. But the other thing was the weight loss. Or I wouldn’t say weight loss, the prevention in weight gain.
Do you think it was going to do that, or did you just think it was going to help with the bones?
Coathup: No, I just thought it would help with the bones. So some of the recent studies we have done with the radiation study in previous ones, have shown that there’s this question that’s raised as flagged in my mind and others as well in other labs is this association between fat tissue and bone tissue. And I think it goes back down to the stem cell. So the stem cell and the precursor cell can either broadly fundamentally, can either go to a fat cell lineage or to a bone cell lineage. And there’s this axis that this drug seems to manipulate in some way. When it goes to fat, it does it at the expense of bone tissue. And if it goes to bone, it does it at the expense of producing fat tissue. And so there’s some connection, I think, between bone and fat that’s gradually becoming more and more interesting. I think as the studies go on, and this study actually really does highlight that because with our animal models, we found with humans, and of course mammals and animals, when you have a reduced estrogen level, you get this weight gain. What was remarkable with our animals was that they were not putting on this fat weight gain. They were remaining quite slim. And it was interesting to see, but why that’s happening, I’m not sure.
And that never happens, like, never do you get a good something and then also a good something over here. Especially when it comes to meat.
Coathup: Yes. And it seems you’ve got the visceral fat that’s around the organs, which is particularly bad because that’s associated with various diseases. And then you’ve got the subcutaneous fat layer, and both of those we found were reduced as well as the fat within the bone. So it’s working well, but exactly how it’s doing it, I’m not sure. The drug that we’re using is a metabolic agent, so it boosts the metabolic activity, and it works in about 500 different enzymes, very important processes. So it’s likely happening through boosting metabolic activity. So now, one of my key things is sleep is a good diet, is exercise, because now based on some of the results that we’re seeing, I think increasing that metabolic rate or keeping a high metabolic rate appears to be really important. The other thing as well with the drug that I don’t know, it could definitely be the metabolic activity that’s increasing, and this may be linked or not. I’m not too sure at this point. But in terms of the fat association with increased fat levels, it could be that it’s somehow reacting with a group of lipids called sphingolipids, which is a whole area that’s very complex and not very well understood, but are associated with various diseases. And so it’s possible that it might be that and that’s future work that we’re going to look at to see if that’s the case.
And right now, there’s no really good long-term drug that doesn’t have bad effects for treating osteoporosis, right?
Coathup: That’s correct, yeah.
Why can’t you be on these osteoporosis drugs forever?
Coathup: So with the osteoporosis, there’s various ones. The main one really are the bisphosphonates. So the Alendronate or the Fosamax that’s often distributed. The main reason is they target osteoclasts, the bone resorbing cells. So what tends to happen with osteoporosis is you have this imbalance in your cell activity, again, broadly and fundamentally. And so the Fosamax and the bisphosphonates, they target the osteoclast and switches it off. And this imbalance causes problems in the longer run, where you’re more susceptible to what we call atypical fractures. So we are looking for alternatives to the bisphosphonates, as well as some of the other drugs as well as various inhibitors and monoclonal antibodies that are relatively new to the market. That are proving effective for bone, but again the long-term use and some side effects are being investigated at the moment. So we are looking for new products.
So could this drug be something that all women take once they hit menopause?
Coathup: Yes, I hope so. So this is a drug that hasn’t really been looked at in bone before. We are new to that research area. It has been looked in Europe degenerative conditions, Alzheimer’s, Parkinson’s, and a lot has been done in the past with very successful results. And in that process, they have looked at this drug before. They’ve shown that it’s got high oral bioavailability. So it’s got good promise in a tablet form, but it’s also been looked at in extended periods, and it’s so far shown to be safe and nontoxic. So I’m hopeful that so far it’s looking like it’s a safe alternative, but there’s still lots to do, of course.
Has this drug been approved for things like Alzheimer’s and dementia and things like that?
Coathup: This, I’m not sure about. So yeah, I’m not sure about it. I’ve been trying to trace it and one of my grumbles is that when it goes through into the clinical trials, they change the names and they give them code names and I don’t know what exactly the drug is or at least I haven’t been able to find out, so I’m not too sure. I suspect one of them is in trial for ALS, but I’m not 100% positive.
Can you tell me about the problem of brtttle bones in menopause?
Coathup: So maybe some figures. So with osteoporosis, it is an issue. So it’s an issue number one because we don’t have good therapeutics to prevent or manage osteoporosis. It’s of concern at the moment because of our aging population. So at the moment, we have a rapidly expanding aging population globally. With our elderly population, 65 years or above, we have an expanding population. But also when we think about what is term as our oldest, old, so people who are 85 years or older, that population is thought to triple by 2060. Then we’re expected to have half a million more centenarians by 2060. We’re going to have a lot more people who are active, I think, but who will have osteoporosis. Going back to the fact that we haven’t got anything to really prevent or treat it, I think is something that’s high on the list at the moment. Globally, we have 200 million people who live with osteoporosis, in the United States, it’s about 10.2 million, about two million of those are men. We have about 1.9 million fractures per year. That’s estimated to increase to 3.2 by 2040, I think it’s something that is increasing because of the aging population. At the moment, in the US yearly, the figures that I saw was that healthcare spending 10-17 billion per year on osteoporotic related treatments and therapies. It’s something that is enormous and I think something that we need to find, something that can help with these patients.
Maybe I’m taking a big leap, but when you go to excess weight and you go to the older population and then you go to knee replacements, and hip replacements, is this something that could benefit all of this? Because it seems like the more weight you have, the more pressure you’re putting on your joints, the more you’re getting arthritis.
Coathup: No, you are right, I hadn’t really thought about that. Only because I think the weight gain part of it is, I mean, is exciting, but maybe because I haven’t understood it so far. But certainly the weight gain is a problem and you going to obesity, which again, is something that is, increasing because of, I think mainly diet in the Western world and other places in the world now that it is putting excess weight on, and it does affect osteoarthritis and it does affect the outcomes of knee and hip replacements. You’re absolutely right. I probably, I’m not seeing the drug as a prevention in weight. I don’t want to say weight loss, but as a prevention in gaining weight. But it potentially could be and have other orthopedic implications.
Now, from your studies, what has been the most surprising? Do you have any really specific numbers or anything or anything really specific you can share?
Coathup: Do you mean in terms of the results? You mean like fold changes or something? No, let me think, so for example, one of the things that we looked at with the animals was we looked at the changes in the blood and the serum, and the proteins, and the bone of course. One of the other things that we looked at was the gut microbiome. That also was really exciting and intriguing to get that data. What we found, I mean, there’s millions of beneficial bacteria in our guts. We know now that the gut microbiome is so important to our health and potentially involved in disease. We had a look at that and we divided the various bacteria families. We found that with the P7C3 we had an upregulation in a particular species that’s in there. A species that we know is involved anti inflammatory processes or is important for anti inflammation. Particularly that species has also been shown to regulate the fat bone axis, so it’s remarkable and somehow the drug was affecting that. Also there was an increase in a particular species or in fact this time a family of bacteria where we had a decrease is associated with obesity, but the P7C3 increased that particular species. Then we found that with another particular bacteria, bacterial species in there, there was a six fold decrease caused by osteoporosis. But we had an increase with P 7C3, and that particular species is associated with frailty, with elderly patients with osteoporosis in fact, and this P7C3 actually upregulated that. There’s a clear link between, I think, the gut microbiome, weight gain, and then bone structure in osteoporosis exactly how that all combines, I’m not sure. I think it can come back to metabolic activity which again, is one of the ways in which I think this drug is working. But nevertheless is remarkable and I was happy and excited by the results because a lot of it I wasn’t expecting to see.
What’s next for this?
Coathup: Oh, that’s a good question, so there’s so many angles. I think what’s probably next for this is. Fragility fractures is an issue we want to prevent those thinking about those patients and people who maybe have had a fracture. One of the issues and challenges is for patients to replenish or to heal that fracture. That’s sometimes because of aging and because of our processes that can be reduced. It would be really interesting to have a look to see whether or not P7C3 can help to repair those fractures in osteoporotic animals. I think that might be the the next step.
Do you think, in the long run, this could just be a supplement that you take?
Coathup: I hope so the reason I say that is because at the moment we’re getting a lot of tests that show that it’s nontoxic. Of course, there’s more steps to take and more to investigate, but at the moment it’s looking promising. I would hope so it seems like, I think again, working through the metabolic activity route, it’s probably having an effect on many aspects of the body. One of the things that I think with the weight gain, I think my thoughts are that’s a stress response. I think with the osteoporosis, you’ve got a disease in the body, you’ve got a stress response. I think maybe one of the responses by the body is to develop a fact issue in order to have an energy source at hand. I think that maybe by balancing the metabolic activity with the P7C3 somehow that stress response doesn’t happen. We don’t have this build up, this accumulation of fact issue ready for a disaster to happen the body’s prepared for some disastrous outcome or stress response really. I wonder whether it could be that, and therefore one of the things for the future actually is maybe then connecting this because it’s already been associated with having a beneficial impact on other elderly conditions such as Alzheimer’s and Parkinson’s traumatic brain injury for example. There seems to be a common thread where this may be an important drug for aging and elderly populations for many aspects of the body, and that’s very exciting.
END OF INTERVIEW
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