The Aging Brain: Challenges and Opportunities in Neurodegeneration and Neurotrauma | LSI Asia '25

Daniel Teo  0:05  
All right. Welcome everyone. Welcome to all those in the audience here at LSI 25 Asia, as well as those who are joining us online around the world. This is the panel on the aging brain today. My name is Daniel Teo. I'm managing partner and co founder for Honeywell Lake ventures. We are a medical device fund that invests in the cardiology, neurology and surgical oncology space. Now you would ask, why those three areas? Well, when we are considering the scope for our third Fund, which is our current fund now we pulled our LPs and potential investors and asked them, what were the three most worrisome health concerns that they have. And consistently, the answers came back, cancer, the heart and neurological health. I mean, those were the three things that worried people the most. Everything else was sort of survivable, right? And so therefore that became the foundation, the three pillars for our current fund. Now, aging health is certainly a problem. You know, I've got some statistics here. You know, the who you know says that there are about 55 million people around the world suffering from dementia in the US, one in nine persons, or 11% of the elderly above 65 years old, also suffer from Alzheimer's. That's 6.7 million patients. So certainly, you know, neuro degeneration and neuro trauma is placing an enormous strain on just caregivers and also the health systems. And don't forget TBI when we're talking about neuro trauma in the US, there are about 1 million cases of TBI a year, and we all know that. You know, those who suffer TBI also two to five times the higher risk of suffering from dementia. So these are all concerns and problems that I think we can we have a solution for and we are trying to address. So today, we are glad to have a diverse and stellar panel with us, comprising physicians, investors and entrepreneurs and even patients, and to share their insights and their experiences in this field. I would ask that the panelists introduce themselves briefly, say something about their connection to the topic, and also a personal statement about the topic, maybe starting with Jody.

Jordi Parramon  2:33  
Ai, yeah, thank you. Jordy Paragon, yeah. I'm the co founder and GP of a new venture capital firm that is called Nexus neurotech. And it's a very kind of mission oriented firm where, where there's a stream of just stream focus in a few clinical indications, all within the brain, one of your three pillars. So we only do one miss brain, and within that just a subset of training medications first that have a really high level of interest by the LPs to for us to pursue. And so we we are. We're looking at opportunities in the space of Parkinson's disease, autism and bipolar disorders in terms of the stage of the companies doing best we go is we go all the way from seat to pre IPO. So essentially, we're not limited by the size of the check more by the strategic faith that these companies have into the things that we really want to do, which is providing better solutions for the patients of the disorder just mentioned. Thank you. Jordan Caitlin,

Caitlin Morse  3:52  
sure. My name is Caitlin Morse. I'm the CEO and co founder of BrainSpace. We are starting with managing brain pressure, and that's done with CSF diversion, about a third of the patients that need that, it's for neurodegenerative cases. So we are looking at the aging brain, and then we're also really looking at on the neurotrauma cases. What can we do in the acute case, when those patients are in the hospital, to make sure they're not dealing with some of the comorbidities you were just describing that lead to increased chances of dementia and other challenges in old age. And so we're really looking at that both from a therapeutic perspective during the acute case as well as what can be done more preventatively as we move forward, we have a device that we recently submitted to the FDA for and are going to be moving into clinical use.

Daniel Teo  4:34  
And Branden

Branden Rosenhan  4:37  
Branden Rosenhan, I am a critical care physician turned venture capitalist at Med mountain ventures, where a pre seed, seed venture fund that's health care focused. Of course, we health care conference, health care focused. We do do med tech, we do digital health, we do services. We the only thing we don't do is Pharma. So happy to be here. Yeah.

Daniel Teo  5:00  
Yeah, excellent. Let's jump straight right in. Let's talk about unmet clinical needs. Brendan, as a critical care physician, you also ran a network of ICUs around the country, in the US. I mean, what do you and your colleagues see as the greatest unmet need in this space?

Branden Rosenhan  5:16  
Yeah, so you know, going back to so I also was a patient. I had a hemorrhagic stroke and a TBI. So I've been both a physician taking care of ICU patients, you know, for more than a decade, and then I became a patient. And so the thing that has not changed in intensive care units much is the way that we get the patients out of the ICU. So there's new therapies, but they're not across the finish line. They're not game changing for hospitals. So the unmet needs are many. For example, we still the solution to delirium in the hospital is the most significant outcome is by keeping the window open and having the people understand how how they should really feel and in the processes. So the long story, the short version, is we have huge unmet needs. We haven't changed how we take care of hospitals, or how we take care of patients and hospitals significantly for a long time, and we need to do that better, because in 10 years, our hospitals will basically be intensive care units. You have to get these patients out of the acute care setting in a number of days, or they're going to have significant comorbidities and significant development of dementia and other

Daniel Teo  6:32  
problems. Okay? And today we are talking about the aging brain. We're talking about the elderly. I mean, does the clinical trajectory for an elderly patient, is that any different from a younger patient? Or are they very you treat them very differently? Yeah,

Branden Rosenhan  6:47  
I'll have to, sort of, I'll be criticized, you know, whoever sees this, or if it ends up on LinkedIn. But with my patients, I always sort of said that it was the kind of I worked it in a long term acute care facility as well, so that when the patients leave the ICU, we think, Oh, they're going to be fine, but you're looking at months of recovery. So I used to tell patients, if every day you're in the ICU, you're reducing your strength, in your return, your rehab for like 10 days. So it's sort of like a one to 10 ratio. If you've been in the hospital for nine days, it's going to take you 90 it's going to take you three months to get back where you were. And so the elderly are going to continue to struggle. They're already having atrophy. They're already struggling with their simple day to day app their daily activities. So yes, elderly will continue to struggle where the younger can bounce back,

Daniel Teo  7:41  
right? So slower recovery. And I think I guess diagnosis may be complicated as well, because they tend to have comorbidities as well, right? You know, they present themselves with a number of other other issues, so being able to clearly identify neurological dysfunction may be trickier than than normal, is that, yeah, yeah,

Branden Rosenhan  8:03  
your neurological impact can be from multi organ failure, from sort of impact the kidneys, you've impact the GI system, then the neurological components are significant. Still it can be anyway.

Caitlin Morse  8:18  
So there's a saying in neuro you injure the brain you have. But the problem is, most people don't actually know the state of their brain is before that injury, before that trauma. And the older you are, the more likely it is that there's other things going on, right? So we've talked about specific comorbidities, but there's also related to atrophy, related to cellular regeneration, related to elasticity, and so one of those challenges also comes into play is you don't actually know when somebody is arriving at the hospital, what their pre state was. That's going to influence all

Daniel Teo  8:49  
those outcomes as well. So I mean to the entrepreneurs who are out there listening, clearly, then this suggests that in designing a solution, you need to take all of these into account and find a way to partition or separate or identify these comorbidities, right, to clearly isolate the disease.

Branden Rosenhan  9:07  
And Jordy has a great, you know, he's the expert on a lot of this components. And obviously the panel, the last thing I'll say is that the, well, see, there you go. There's my, my, I forgot what I'm saying.

Daniel Teo  9:22  
All right, Jody, you about to jump in? Yeah. So well,

Jordi Parramon  9:27  
a very obvious, gigantic clinical unmet need is having disease modifying interventions for these neuro degenerative disorders that just progress over time. This is like, if there's one single biggest opportunity to really make something as transformational is figure out a way to slow down the progression of the disease, or even reverse them. Alzheimer has started doing that a little bit with some drugs that reduce the amyloid plaque, but still, the clinical effect they have is small. So the future of neuro Inter. Engines will have a very different scenario where there will be options to choose that can start making a difference in the progression of disease. That's that's what we need.

Branden Rosenhan  10:11  
Okay, yeah, and now that you reminded me, so when you're a physician, diagnosis drives therapy, and you've nailed it that we have these kind of therapies and but we're just learning there's there's really good diagnosis, there's really good monitoring that's sort of been invented in the last decade. So we're seeing, but we're not going to improve significantly until we have great therapies. Yeah.

Daniel Teo  10:36  
So the starting point for any kind of therapy must be sort of data and knowledge. And the earlier we know what's going on, and the more we know what's going on, we have a better chance, or physicians have a better chance, of addressing the issues, slowing the progression of the disease, or even treating them right. And CSFs and blood are two rich source of biomarkers for neurodegenerative diseases and neuro trauma. Caitlin, your company, you spend a lot of time working on developing a solution for managing not just intracranial pressure, but also CSF. So what are the opportunities that you see here in this area?

Caitlin Morse  11:17  
Yeah, absolutely. So, as Brendan was just saying, the it is a bit of a chicken and egg scenario, right? Because from a clinical perspective, if you don't know what treatment you're going to do differently, it's hard to justify that additional monitoring, that additional testing, the sampling, the biomarkers. On the other hand, if you don't have a way to stratify your patients, then when you get mixed outcomes, you don't really know. Was that because you had a heterogeneous population, or is that because the therapeutic was not as effective as it could have been? And so one of the things that we're really looking at, and I think there's a real opportunity for in the this next phase of med tech, is really to be data rich as a secondary benefit while providing a primary therapeutic benefit. And so we really look at that as there have been over 3000 publications around CSF biomarkers in the last 20 to 30 years. There is significant scientific work being done, but until that translates to the bedside, it's not really making the impact for patients that we all want it to see. And so I think we have a real opportunity, whether it's vagus nerve stimulation or dBs, on the electoral side, whether it's CSF drainage, and some of the things that we're doing is what data is being collected that helps better inform the populations that are benefiting, so that we can then decide where those therapeutic pathways make sense. And so we're excited about that. On the CSF biomarker side, we think there's a lot of opportunities in neuro inflammation. And specifically, in the last 20 years, there has been work on what is dementia specific, what is Parkinson specific, and that has been metabolic protein based. There's a number of different types of bio sensing that's going on, but we really see that the time has come to be able to integrate those in a way that is meaningful therapeutically

Jordi Parramon  13:03  
and just to follow up on that the importance of biomarkers are not just from a diagnostic perspective. Having a yes no that you have a disease, this is an important first step. The value of biomarkers will be amplified once in the future you have good interventions. Then if the markers can make a measurement of the progression of the disease, then you can integrate it into your algorithm, and then, and then, with that, you can optimize the personalization of the intervention. So that's that's one thing which is super important, to look more for a quantitative marker than just a qualitative marker of yes and no. And your point you were making on data integration as a way to really have a role in how we manage this patient is, is very important, because, because the patient and that you go home, you live your life, and before the emergence of all these wearables and technologies that can have a sort of visibility of what you're doing, then you couldn't really do anything. But now that we have watches and phones and connectivity, internet, etc, all these digital elements that surround oneself can actually be used to manage better the disorders. Like one of the companies in our portfolio is called room labs, and he's uh, is on Parkinson's patients. Is a is a multi model data platform that, among other things, captures tremor and dyskinesias from the Apple Watch. And the Apple Watch is connect the phone, and the phone is going to get to the specialist if you need it or to now to these agents, AI agents, right? They provide lower head services. And it's a complement of what will also be a therapeutic piece as well, that the two things will work synergistically to improve the life of these people. Yeah.

Caitlin Morse  15:00  
Yeah, absolutely. And that's actually, we've talked with a number of companies who are doing more the non invasive or class one, and really looked at, how can we do studies together where we quantify, okay, here's what was happening in the acute phase. Here's what it looks like six months later, right? And really be able to see that full patient journey. And the more that that's quantitative, we can address interoperator variability, we can address a lot of okay, well, in this environment, it looked this way, and I think there's really an opportunity to paint that whole picture, and that's where the wearables and the non invasive as well as the obviously more invasive therapeutics, can really go hand in

Daniel Teo  15:34  
hand. And I think what I'm hearing is that biomarkers are helpful, of course, but they're useless if they don't result in actionable clinical Yeah, you have to, you have to do something with that. You got to do something with that. So let's, let's move on to neuro diagnostics. So you know biomarkers, CSF and blood, of course, one way to access these biomarkers. Are there any other technologies out there any other ways of accessing these biomarkers and identifying them that you're aware of? Are there any other technologies out there?

Caitlin Morse  16:08  
I mean, it depends kind of how you define the term biomarker. There's actually a fair amount that's done in digital biomarkers as well. So you think about this on the physiological level, but even digitally, some of the derived biomarkers that exist from those parameters can be done. So it isn't just the biological analyte side, and that's actually where a lot of the Apple Watch type stuff comes in. Is really more as a digital biomarker.

Jordi Parramon  16:30  
I also add so on the imaging side, right now, you have MRIs in one side, which has a lot of resolution in the space, especially, you can see very little things, but very slow. And then you have EEGs, which don't have spatial resolution, but you see signals very quick. Ideally, you would like to find something in the middle where you can actually see how the brain behaves, non invasively, with a time scale that you can attach it to labeling text that can be useful to understand better. So if any one of the entrepreneurs has ideas how to develop this kind of technology, that it's something that's needed, you're

Daniel Teo  17:09  
talking more like a functional MRI kind of thing. Fast

Jordi Parramon  17:13  
function. It's very slow. Real time results, real time MRI. That will be the ideal,

Daniel Teo  17:19  
right? So for the audience, the entrepreneurial audience, you've heard it real time. Functional MRI is this kind of what we're looking for. Earlier we talked about different, you know, the publication of so many different biomarkers, right? There's amyloid, there's tau, there's kitten, a series, a whole bunch of these, for amyloids in particular, for instance, there, there are at least, we're aware of at least three or four companies that are now trying to identify amyloid deposits, or Amyloidosis through ocular amyloidosis, so through the eye. So you know, the next time you go and see your optician or your optometrist, you know you could not, you know, in addition to just getting your eyes checked for for clarity and all of that, you may also be doing a dementia screening or an Alzheimer's screening, right? So those, those are the kind of technologies that are out there. Anything else on Diagnostics, anyone wants to add?

Branden Rosenhan  18:16  
I think that they both sort of nailed it. I mean, you in your diagnosis, your diagnostic or monitoring has to be able to be sensitive and specific, and it has to be able to do so quickly. And if you don't have a therapy, you know, we were, she and I were discussing last night that, like she has this awesome data coming of what's going on in the CSF, what does it look like? How can I optically provide information, and I could do it real time, or I could, and I sort of kept saying, but what are you going to do with the result if it's in this kind of ties into what Georgie said, what Geordi says, if the result comes in five minutes, what are you going to do differently? If the result comes in five hours, what are you gonna do differently? Somewhere from from the physician side that I taught these young the training doctors. It's like, okay, why are you going to order this lab? Well, I ordered it yesterday, and I want to know what's going on. I said, Will you do something different? If the result is different, you shouldn't draw the lab again. So we have to have real time information that we can act on. You've said actionable before, so I think Georgie is right if George, sorry, keep saying, Georgie. George,

Daniel Teo  19:25  
okay, so let's, let's talk about action. Then let's talk about treatment and therapies. You know, one approach is, of course, surgical, but nobody likes to have their brain crack open for for something like that. So the trend is towards sort of neuro stimulation, minimally invasive, sort of therapies. Over the last two years, we had Honeywell, we have been curating a group of companies for our investors, and we see an explosion of activity in the neuro stimulation, neuromodulation space that's really sort of. Intuit from, you know, two, three years ago, where you're seeing, most of what you're seeing are sort of consumer grade pain management devices, the type that you see at a Consumer Electronic Show, right? With dubious some of them, many of them with dubious claims, dubious clinical claims. To now graduating to clinical grade devices. They're all coming of grade, coming of age. These are, you know, vagus nerve stimulation, some deep brain stimulation, transcranial stimulation, sacral nerve stimulation, addressing not just dementia, Alzheimer's and stroke rehabilitation, but even things like bladder control and erectile dysfunction. So there's an explosion of these. Jordi, what other opportunities do you see in this space?

Jordi Parramon  20:51  
Well, I, for I started working in the space in the late 90s. So if you ask me, then neuromodulation, if you ask me at that time, how would the future would look like? 25 years from today? We just today. I was imagining that we'll be having Neil Mont everywhere, and the reality is we don't. I think we screwed up big time the industry wise, because we've been focusing a lot in a very few indications that have high gross margins, so make good business, but very low penetration. So you look at the number of people that get a deep brain stimulation or or spinal cord, the old disease is still very small. So we have not really tried to address a question on how to scale the those kind of interventions and and I think over time, people are starting to realize that if you don't find ways to scale the business are very hard, right? It's because very capital intensive, very risky, long term. So, yeah, so that's, that's a little bit of the challenge, I think, is how we can make the penetration of interventions go from a one to 2% like 20, at least 20% hasn't happened yet.

Daniel Teo  22:00  
What do we think is the barrier here? I mean, what's keeping this from exploding the way that we think it should? Why isn't it taking

Jordi Parramon  22:08  
off? Well, it depends on so if you look at deep brain stimulation, you need a functional neurosurgeon to the procedure. How many functional neurosurgery are in the US, and what is their growth over time? That's it. There are the same number of centers today than 25 years ago, you're so that's, that's one thing, right, the easy of the intervention. The other thing too is, who likes to have his brain open, right? Put a hole in the brain and put electrodes inside. That's not funny. So the more interventions that will realize invasive that will be more conducive to acceptance, that will be easy to practice clinically, the more of these things will impact people. That's why, for example, we invest in companies that are trying to use this approach as well, like focus ultrasound, this where one of our companies is inside tech, and they doing amazing things. You can target one millimeter of neural tissue deep into the brain, super high precision and and you get your tremor gone without really opening your skull. That's an example.

Daniel Teo  23:13  
Well, since you made a pitch for insight tech, I'm going to make the pitch for synaptica, which is a transcranial stimulation device designed to enhance neuroplasticity and improve brain connectivity and neuro connectivity. And you know, early studies seem to suggest that, you know, for for Alzheimer's dementia patients, 33% showed no progression after the use of device, versus 70% 17% in a placebo. So not quite the silver bullet or the golden bullet, but I think that's, that's an improvement, and that's a solution that's out there for for many people.

Jordi Parramon  23:53  
Oh yeah. I mean, and I know, well, Ken, the CEO that was in Africa, and they have to, and now they are doing this journey of increasing the quality of a clinical evidence with multi centers and more statistics. But I think the idea of using a molecular intervention to force plastic changes that have a memory effect that could reinforce sort of networks in the brain that could have therapeutic value. It's super horrible,

Caitlin Morse  24:23  
to your point as well, about how long it's taken and kind of why are we taking so long, right? Yeah, why are we gotten there? Right now, I think when you ask about what percentage of people are adopting these technologies, one of the challenges when I talk with patients is that if you tell someone they have stage four cancer, there is a pretty clear take action or you die, right? There is, there is a stimulus in that environment to say you must do something. And the question is, what are you going to do with a lot of neurological conditions? The belief right now on where we're going to have the most impact is earlier on, but at that point. They're not facing that level of urgency, and so to do something that feels aggressive and high risk when you're potentially jeopardizing your good years is, I think, a little bit more complicated. So when you think about it from the patient perspective and from the family member's perspective, they're sometimes going to say, well, let's see. Maybe it's not that bad. If it's still getting worse in a few months, maybe we'll go to the doctor. To the doctor, right? And so I think part of the challenge also becomes, if you don't know what that progression is going to look like, knowing what risks you're willing to take can also be a challenge. Yeah.

Daniel Teo  25:33  
So I think we've identified risk and perceived risk at least, and sort of the trauma of having something drilled into your head as obstacles. I would also suggest that maybe even stigma could be a business barrier, right? The fact that even, for, say, a vagus nerve stimulation, I mean, people can can kind of see that there's something there, and, you know, it doesn't feel normal in that sense. And so stigma could also be keeping a lot of people from seeking treatment or making themselves available to the kind of treatment and solutions that are out there in the final three minutes that we have left, I want to ask each one of you, starting with Caitlin, so having worked in this space for such a long time, I mean, What do you and your colleagues, your entrepreneur colleagues, what do you what do you guys excited about in neuro? What do you see as the most exciting things going forward, over the next couple of years?

Caitlin Morse  26:30  
Yeah, I will say, before launching BrainSpace, I had worked in a number of different products that have accomplished a number different spaces. And one of my favorite things about neuro is how much is still not yet figured out. So in the early days, I would talk to an intensivist, or I'd talk to a neurosurgeon. I'd say, Okay, explain to me this. What about that? And eventually go look Caitlin. Nobody really knows. But here's what we teach our residents, and that idea that compared to, say, maybe where Hart was in the 80s and 90s, there's still so much opportunity to be able to make real, meaningful progress for patients, for families, build meaningful businesses. It's still just so much of a blue ocean compared to a lot of other parts of medicine that I think Medtech really has an opportunity to shine here.

Daniel Teo  27:16  
Thank you, and for Jody and Brandon, think about you know, what's as you approach your investments in neurological space, is anything unique that you're looking for in these kind of investments that you might not perhaps look for in others areas. I mean, for instance, for for us at Honeywell, when we are looking at investment in neuro neurological space, beyond the clinical data, which is, of course, important and necessary. We also want to try and understand, if possible, the science behind it. So a bunch of correlational analysis saying, If I do this, these are the outputs and these are the outcomes, is enough for the FDA, but it doesn't quite satisfy our investors. They want to understand the science and the chemistry or the physiology behind it. What do your investors? What do you look for in your investments?

Jordi Parramon  28:09  
Well, the yet mechanistic action understanding is a piece. The problem with the brain is that is any the same time is the opportunity? Is that the science is very limiting. And once you get into this kind of complexity of an organ, which is orders of money to anything else that we know in the universe, on everyone, then then the question is that trade off between how much money you want to spend on the science versus how much money you want to spend on the clinical evidence that you have to generate anyways, right? So then, and that's, that's, I think it's case by case, depending on on, yeah, and

Daniel Teo  28:48  
Branden, 30 seconds,

Branden Rosenhan  28:49  
the short version is, I'm going to be contrarian, is, sort of, is the venture guy, the financial guys. You have to figure out your work on the science, you work on the clinical studies, but there's still always going to be debate on, like, how good that is, right? So you need to think about, how are you going to get not just reimbursed, but create a business that can succeed and that can grow, so that you can then redevelop the science so it is a chicken egg thing, but so that's what's exciting for us. And the things we look at is, really, if you can get off that initial head ledge of creating revenue and making the company succeed, you can do really more exciting things. 

Daniel Teo  29:29  
Thank you. Brenda, then on that note, we conclude this panel on the aging brain. Let us give a round of applause to our panelists and thank them for their insights. Thank you.