Corinn Cross, MD (Host): Welcome to Ped's Cast, a podcast brought to you by Children's of Alabama. I'm your host, Dr. Cori Cross. Acquired hypothalamic obesity has long presented a complex challenge in healthcare, leaving pediatric patients struggling to lose weight. An innovative study involving a medication called setmelanotide aims to address this problem.

Today, we are joined by Dr. Hussein Abdul-Latif. Dr. Abdul-Latif is an Endocrinologist and Professor in the Division of Pediatric Endocrinology and Diabetes at Children's of Alabama and the University of Alabama at Birmingham. Dr. Abdul-Latif is here with us today to discuss this groundbreaking research, offering insights into its origin, mechanism, and potential impact.

Dr. Abdul-Latif, thank you so much for being here today. 

Hussein Abdul-Latif, M.D.: Thank you for having me. 

Host: So let's start with a broad question. Can you give us an idea of what hypothalamic obesity is and how it occurs? 

Hussein Abdul-Latif, M.D.: The hypothalamus is a region of the brain that is above the pituitary gland. The pituitary gland is the gland just behind our nose. And the hypothalamus controls several hormones, but it also controls our satiety, meaning our hunger and our feeling full and our wanting to eat and our wanting not to eat. 

When we say hypothalamic obesity, what we're talking about is that some process happened to that area of our brain that makes the control of our satiety or feeling full or not feeling full or feeling hungry and not feeling hungry, of course, meaning oftentimes when we have hypothalamic obesity, someone has some injury to that area, either by surgery or tumors or whatever, and therefore they end up eating a good bit and not wanting to stop eating. They don't feel full. So that is basically hypothalamic obesity in short. 

Host: What makes it so challenging to treat this particular type of obesity? 

Hussein Abdul-Latif, M.D.: Basically playing with our brain, in a sense, and the patients that have this condition, they really want to eat all the time, and it's very difficult for them to feel full. The other thing that happens to them at the same time, also, because of injury to that area, their basal metabolic rate is lower.

So, you can tell them not to eat, which some of them will say, I am not eating enough, but also their metabolic rate is low and therefore they don't have to eat as much to gain weight. So that is basically one of their problems that they have. It's very difficult to convince someone who is hungry all the time not to eat. I was talking with one of my patients and she felt it's a constant struggle for her and she will break down every now and then. 

Host: Now this might be outside the scope of this discussion, but what you described is injury always occurring at the hypothalamus and it sounds like the injury is after birth. Is there any time when this happens in utero or are children ever born with this or this is always something that happens later? 

Hussein Abdul-Latif, M.D.: So there are some people that are born with genetic mutations with certain genes in certain areas that affect that same pathway that make us feel full or not. And those people will have hypothalamic obesity for genetic reasons. That is actually the first group that was FDA approved to use  setmelanotide in order to treat their obesity with great success.

Now, there are also other people that are born with congenital malformations in their hypothalamus that make them not produce different hormones and also causes that area not to work very well and causes them to be having hypothalamic obesity. And a third group are people with brain tumors or surgeries or accidents or trauma that end up injuring that area and causing them to have hypothalamic obesity.

So it's basically three big categories, genetic as in particular monogenes affecting the area versus genetic as in born with problem in the formation of that area versus our own injury to the area. 

Host: So you mentioned, the drug we're going to talk about, setmelanotide. So you created a study to basically study the effectiveness of this drug on hypothalamic obesity. Could you tell us a little bit about that study and how it worked? 

Hussein Abdul-Latif, M.D.: Maybe to clarify, I didn't really create it. The company, it's the same company, that made  setmelanotide and made it FDA approved for treatment of genetic obesity, causing this, are the ones that are interested in doing this study, looking at hypothalamic obesity, because they're looking at that this is the same mechanism that causes obesity, but it's a, like, same general mechanism, but it's a different process. 

Host: So, they developed the study.

Hussein Abdul-Latif, M.D.: Yeah. Yeah. And it's over different sites in the country. We are one of them. They reached out to us. It's definitely something I wanted to do all the time because I have seen the struggle that my patients had with their weight. And so the moment they approached me, I was very excited about it.

And I reached out basically to some of my patients who are now adults, that are struggling with obesity and offered them to be part of the study and they accepted happily. 

Host: So tell us, how do you take this medication?  

Hussein Abdul-Latif, M.D.: It's injections, and I believe they take it daily at this point. The company is trying to make some other formulation that you can take weekly and perhaps not injections and then kind of we see how they respond to those injections. 

Host: And what have you learned from the study? 

Hussein Abdul-Latif, M.D.: It's very, very interesting. The study is supposed to be blinded, so I am not supposed to know who is taking the medication and who is not. But it's very, very clear, that the patients that are taking the medication, have lost significant amount of weight, whereas the ones that are not taking the medication, they have not lost any weight. 

The  setmelanotide, one of the ways it works, it works on what we call melanocortin receptors. And melanocortin receptors, some of them are ones that make us have pigment in our body. So if you're taking this medicine, it makes look a little bit darker. And so, there are two clues for knowing who is taking the medicine.

The ones that lost a good bit of weight and the ones that got a little bit darker, showed great response to the medication. I would say this medicine is revolutionary, in a sense, for this condition. 

Host: That's amazing. Now, when you talk about the fact that it does affect your melanin, are you noticing that there are side effects of this medication for people who might have like melasma or something where they don't want increased pigmentation? 

Hussein Abdul-Latif, M.D.: That is definitely something that we're watching, not necessarily melasma. It's more of like if they do have some nevus of some sort and kind of like is the nevus getting darker or not? That is something that we will be watching for. The skin itself getting darker, depending on the individuals, some people like that and some people don't like that. 

So you can call it a side effect or you can call it a side benefit depending on -  

Host: Are we talking like a mild tan or is it a very big difference? Would somebody who hadn't seen them in a while notice the difference immediately? 

Hussein Abdul-Latif, M.D.: Yeah, I mean, if it is someone who's very fair skinned, they will get darker and it may look attractive to some of them. If someone is dark, they will probably like get darker. Sometimes you can see it. Sometimes you may not. 

Host: And then are there any other side effects or negative effects of taking this medication? Does it increase your risk of melanoma? 

Hussein Abdul-Latif, M.D.: Not that we're aware of. But that is definitely something that we're watching with this medication. It doesn't necessarily make our melanin like the melanocytes grow or increase. It just makes our skin get a little bit darker, but that's definitely something that long term watching would be important. 

Host: For patients with hypothalamic obesity, is there anything else that you can tell them that can improve their overall health? 

Hussein Abdul-Latif, M.D.: Definitely, like, it's the general health maintenance issues. So many of them do have also growth hormone deficiency, so they may respond from taking growth hormone. They do have thyroid hormone deficiency. They will need to optimize the thyroid hormone doses that they have. 

Many of them, because of the obesity, they develop diabetes, Type 2 diabetes, and therefore perhaps many of them will need to take GLP 1 agonist, which also may help weight as well, but not as well as the  setmelanotide. So, part of the treatment for them is optimizing all of that in addition to  setmelanotide. 

A big issue they deal with, that is part of obesity as well, is sleep apnea, and we need to make sure that they are all being observed or studied for it, and if they have it, they need to receive treatment for it. 

Host: It's just so much to really think about for these patients because I'm sure this is a medication that they have to take basically for the rest of their lives, as well as a lot of the other things that you mentioned because their hypothalamus just isn't working properly. As we wrap up, is there anything else you'd like to share with our listeners? 

Hussein Abdul-Latif, M.D.: A big thing that I'm really excited about this study. I am a Pediatric Endocrinologist that I've been practicing here at UAB and Children's Hospital for 25 years, and I've been frustrated all those 25 years with how we were not able to make a dent in this hypothalamic obesity. So seeing the dramatic results that I'm seeing, I cannot wait until this medicine is approved for other patients and offered to them because it is life changing. 

Host: That's a lot of hope. That's wonderful to be giving your patients. Thank you so much for sharing your expertise with us. This has been such an interesting and educational discussion. I really appreciate your time. 

Hussein Abdul-Latif, M.D.: Thank you. 

Host: If you would like more information about hypothalamic obesity, or to refer patients to Children's of Alabama, go to InsidePeds.org. That's insidepeds.org and search hypothalamic obesity. That concludes this episode of Children's of Alabama Peds Cast. If you found this podcast helpful, please share it on your social channels and be sure to check out the entire podcast library for other topics that might be of interest to you.

Please remember to subscribe, rate, and review this podcast. Thanks for listening to this episode of Children's of Alabama Peds Cast. I'm your host, Dr. Cori Cross.