Pioneering Innovation in Neurodegenerative Disease Research with Dr. Tom Otis
Brendan Aylward (00:02)
All right. Welcome to the AdaptX podcast where we have conversations with individuals who are building accessible businesses, advocating for inclusion or excelling in adaptive sports. Our intention is never to speak on behalf of those with disabilities, but give them a platform to amplify their voice.
and share insights and information that can make your world more accessible. Today, we are joined by Tom Otis. He is a researcher, academic and author. He is the chief scientific officer at Lariotherapeutics and is a professor of neuroscience at the University College of London, where he also serves as the chief scientific officer at the Sainsbury Welcome Center for Neural Circuits and Behavior. His background spans 30 plus years of experience in both academia and industry. Prior to his university position, he led a team of 45 scientists conducting early stage drug development in neurodevelopmental disorders
in psychiatry at Roche Pharma R&D in Basel, Switzerland. Before Roche, he served as the Edith Agnes Plum Chair of the Department of Neurobiology at UCLA. Tom received his bachelor's and master's degrees in biological sciences and his PhD degree in neuroscience from Stanford University. His research is focused on cellular and circuit function of the cerebellum and hippocampus, motor systems function and motor learning and preclinical models of epilepsies.
Spinos cerebral ataxia and amyotrophic lateral sclerosis, better known as ALS. Probably the most impressive and lengthy intro I've had so far and I only butchered a few words, so I'll call that a win. Tom, thanks for joining us today.
Tom Otis (01:32)
That's my pleasure, Brendan.
Brendan Aylward (01:34)
All right, let's dive in. I'll do my best to keep up. So for our listeners who might not be familiar with SCA, so spinal cerebral ataxia, or ALS, can you maybe provide an overview of what they are, maybe any intersections or individualizations?
Tom Otis (01:51)
Yeah. So I'll start with Spina Cerebellar Ataxia. These are diseases of uncoordination and they're neurodegenerative. So parts of the nervous system, the neurons die and this causes the symptoms. And these neurons are mainly in a structure called the cerebellum, which is critically important for coordination, coordinated eye movements, balance, and motor learning.
So in sport, this is a part of the brain that's really important. And these diseases, the other thing that kind of sets spinocerebellar ataxia as a part, see, even I can't say it, is that they are predominantly genetic. So there are genes that cause what we call a gain of negative function. Just means that the gene is doing something bad.
Brendan Aylward (02:33)
Tom Otis (02:48)
and it's doing something bad that affects, in particular, these neurons in the cerebellum. Hence the disease. In ALS, ALS is a disease of motor neurons. So these are, it principally strikes the motor neurons in the spinal cord and in the brainstem. it's also degenerative. And so these neurons die and people gradually become unable to move.
So they become gradually paralyzed. In ALS, it's quite interesting and similar to some of the other major neurological disorders in that we know many genes now that can cause ALS. So about something like 15, 20% of ALS cases are caused by known genes, single mutations.
And then the remainder of ALS cases are complicated. They're unknown origin. They might be many genes that are kind of together on failing to cause the disease.
Brendan Aylward (03:56)
The introduction of CRISPR allowed you to more accurately assess the genome. Has the nature of your research changed a lot since that was introduced?
Tom Otis (04:09)
It has in the sense that it's a tool for not only potentially, not, you know, maybe not quite yet, but potentially for transformative medicine to edit genes. Um, that promise is there. there are a lot of people working on this, a lot of companies as well. Um, but it's a tool that's important for research. So it enables you really to, to go in and with precision, rewrite, a genome, either a part of a gene,
and correct, for example, a mutation or to remove a gene or to alter it in a certain way. So in exploring these things, the biology of these things, it's a huge and important tool. Similar to many, many people remember the PCR technique, which heralded an explosion and forensics and study of the human genome where you could really amplify small parts of DNA.
Also human origins, right? Fossils and Neandrotals and all that. PCR about 25 years ago, I would put CRISPR as a similar transformative advance.
Brendan Aylward (05:18)
What influenced you to kind of delve into the field of neurodegenerative diseases? Was there any personal experiences that influenced that career path?
Tom Otis (05:32)
You know, when I was making the kind of the real early career path decisions, when I was studying at university, neuroscience was fascinating. So I was first hooked on neuroscience and actually that happened or key events. When I, when I was an undergraduate, I actually was really captivated by Jacques Cousteau. And so I wanted to be a Marine biologist and Stanford has a Marine station.
beautiful part of the California coast in Monterey. And I studied there, I went and studied there. And part of the lab work was with sea slugs and squid and things like that. And these were at the time, this was in the mid 80s. These were classic preparations where you could study neurons and neural function. And so I, you know, I kind of became fascinated with how neurons can
can work and signal and they form the basis of not only movement and all action that we take but all the cognitive stuff and memory and all of that. So then I went to graduate school and I learned because it was a lot interspersed with the medical students, I learned a lot about diseases in the nervous system and they're of course they're devastating and it's really a mystery even still.
many of these diseases, we don't have a good understanding of what's gone wrong. Like most people, I've had relatives who've had certainly age-related dementia and other sort of insults to the nervous system.
Brendan Aylward (07:23)
Yeah. What are the biggest challenges? I know there's a lot of unknowns, and this might be too vague of a question, but what are the biggest challenges in kind of identifying some of the epidemiology and the genetic causes of these conditions?
Tom Otis (07:37)
Yeah, well, I mean, I'll talk first on a positive note. There's a lot of unknown, and I'll get to that. But on a positive note, the advances in genetics, starting with the human genome in the early, mid to late 90s, advances in human genetics have really been incredibly advancing for medicine, for our understanding of disease, designing treatments for disease.
I mean, really now we're in an age where we can have quite precise therapies and really effective therapies and specific diagnoses, right? Not catch all diagnoses. So an example of that, a really great example of that is in cancer therapy. I mean, 10, 20 years ago, cancer was really a disease where patients had...
you know, radiological therapy, they had surgeries, they were really kind of go and get the tumor or try to kill it with either a chemical poison or a radiological poison and hope you don't kill good tissue and bad. And now with an understanding at a genetic level of cancers, there are many cancers now where we have precision medicines or cell-based medicines that are much, much more effective.
Jimmy Carter, you know, president who died recently, he would have died 20 years ago without these advances in therapy as an example. So coming back to your question., what don't we know and what are the challenges? Well, in the nervous system and the brain, all this is harder because, you know, it's inside your head, you have a barrier from the blood. So getting drugs into the brain is harder. Obviously, if you want, if there were a tumor, like a glioblastoma, a terrible tumor,
And that's in your brain. It's much harder than if the tumor is in your liver where you can do a biopsy or on your skin Where you could do a biopsy in an outpatient office and that biopsy could tell you about the genes That would then allow you to pick medicines off a shelf in the best case in the brain Much harder, right? So These are big challenges, but I do think you know things that we learn.
Tom Otis (10:00)
about biology elsewhere in the body can also really lead the way in the brain. And oncology is a good example. I mean, I think glioblastoma treatment will certainly has and will certainly benefit from, for example, oncology of solid tumors in the body.
Brendan Aylward (10:17)
There's a couple FDA approved treatments for ALS, but I guess treatment, they're not treatments, but they slow down the progression of the disease. So if there's nothing that can reverse it, but there are some options that slow it down, what's being done for earlier detection of ALS?
Tom Otis (10:36)
Yeah, I mean, these are this is, I think, a very fair assessment. It's not what we have in terms of therapeutics is just the beginning, and they're clearly not good enough. And what I would say is that, you know, this is a very active space, ALS drug development, things that your audience might want to keep their eyes on. There are, as I mentioned, there are genetic forms of ALS. So there are
let's say, you know, half a dozen to a dozen genes, where mutations in these genes will cause ALS or are very likely to cause ALS. And these genes are being several of them are being very actively explored as targets for therapies. So one of the recently approved drugs is against a gene called SOD1 one.
and this is a program that Biogen led, Biogen and Ionis, I think. And the SOD1 gene has a so-called gain of negative function. So the gene and people who get SOD1-related ALS, the gene causes bad, it has a mutation that causes bad things unrelated to its normal function. And the therapy is simply to prevent
that bad gene from being expressed as a protein. Okay, so it blocks the effect of that gene. And that therapy was approved by the FDA, and it's interesting, it was such a transformative therapy that it was approved even though the clinical benefit is probably not great yet in terms of outcomes, but the fact that they could show they could remove this
This gene they could target it and they could do what they needed to do molecularly was enough and I mentioned that as a story because that shows you that the field, you know, the field is on the march and for many of these genes I think there will be some success in mitigating the terrible outcome of ALS
Tom Otis (12:57)
And it probably will, you know, it'll take some time. And you see this with Alzheimer's disease as well. You know, the first therapies, they didn't really work. They were controversial. Now it seems like they're starting to work. I expect that momentum to continue. It's a natural question to think, okay, if you develop a therapy for a genetic subset of ALS patients, is it only gonna work for those patients? And those are things we have to learn. I mean, you could argue this both ways. It might be that some of these targets
will be effective for a larger fraction of the patient populations, not just those who have the bad genetic form, but that has to be established. So I think there's real cause for hope and there's a lot of really specific and I think very, well, precise incisive paths that are being explored.
Brendan Aylward (13:55)
You mentioned, obviously there's a genetic component, but also a variety of other.
factors that are somewhat unknown, maybe some are known. Are you familiar with a study from a few years ago that looked at the association between NFL players and ALS diagnoses? Yeah, so saying something along the lines of people are four times more likely to develop ALS if they played football. And I think there was also a correlation between the length of career and the severity of ALS. So is repeated head trauma one of those confounding variables?
Tom Otis (14:12)
Yeah.
Brendan Aylward (14:31)
If so, between the research that's been produced on CTE and stuff like ALS, do you think the public is taking that seriously enough?
Tom Otis (14:42)
No, I mean, I think anyone would have to say that this has been shocking and that the alarm, if anything, the alarm has mounted. I mean, I'm a sports fan. I, you know, I like to watch the NFLs, but I will say that it's, it is extremely alarming that, and it's extremely clear that repeated, repeated and strong force.
applied to the head like you have, and certainly in pro football and in boxing and some other sports, we have to really think about what we can do to limit that because it is very dangerous. There's a lot of overlap, interestingly, between these kinds of chronic traumatic encephalopathy mechanisms
There are diseases that, neurodegenerative diseases that are often called misfolded protein diseases. These diseases include ALS, Parkinson's disease, Alzheimer's disease. And in chronic traumatic epilepsy, chronic traumatic encephalopathy, you see similar neuropathology to some of these other diseases.
So the neurons get, they look in histopathology like some of these other diseases. And we don't understand exactly why, but probably at the cellular and molecular level, there are similar things happening.
Brendan Aylward (16:24)
Are you collaborating then with people who are researching Parkinson's, people who are researching Alzheimer's? Is there overlap in your research?
Tom Otis (16:34)
There's definitely overlap in Parkinson's disease. And I mean, I have many close colleagues and I pay fairly close attention to the Alzheimer's disease literature, particularly, I mean, and you could probably sense this. I personally particularly think that genetic clues in terms of genes that...
Tom Otis (17:02)
genes that are implicated strongly in rare forms of these diseases.
Brendan Aylward (17:12)
Tom Otis (17:17)
I mean, it's not bad now. It's not too chilly. It's maybe, you know, it's maybe 50 degrees or something here. And you can see if you look out the window, you can see sort of there's a big tower there. I'm just in central London. It's called the BT Tower.
Brendan Aylward (17:26.312)
What's the weather like in London this time of year?
Brendan Aylward (17:36)
Oh, okay.
Yes, no. Yeah.
Tom Otis (17:47)
Yeah, so it's the weather. I can't complain. It's not raining, which is nice.
Brendan Aylward (17:54)
Yeah, training for the marathon and we've been getting snow, etc. That's made running a lot of miles, not super comfortable.
Tom Otis (17:58)
Well, I was in mid January. I was, in Massachusetts and New York and it was really cold.
Brendan Aylward (18:05)
Oh, were you? Nice. Yeah, yeah, not great. All right. What were we were saying? Overlap between ALS, Parkinson's, Alzheimer's.
Tom Otis (18:16)
Yeah, and I was just going to make the point that the genetics, the human genetics, even in rare and small subsets of Parkinson's disease, ALS, Alzheimer's disease, that these rare genetics are really important for drilling down into a mechanism and identifying possible therapeutics. I think this is a really exciting area of modern medicine.
And it's not just me that thinks this because when you, you know, for example, in some of these genes, researchers have discovered not only versions of the gene that will cause the disease, where if you have a genotype of someone when they're 30 years old, you know they're gonna get the disease when they're 55 or 60 years old. Okay, so it's very powerful, you know, very...
predictive in a classical genetic way. So that tells you the gene could contribute to a disease process. But in many cases, there are also versions of those same genes that protect individuals against the disease. So if you look population-wise, there are other mutations in the same gene, and people will, on a population-wide level, they'll be protected against a disease.
even a kind of non genetic form of the disease, right? So those two things together tell you that gene deserves attention, right? And maybe a therapy to make, for example, to make the bad version of the gene, the sequence of that protein into something like the good version, right? That's a natural, logical thing to do.
Brendan Aylward (20:06)
We've talked about post polio syndrome and MS on the podcast as well. My father was diagnosed with MS when I was in kindergarten.
through therapeutics has the progression of his condition hasn't worsened drastically or as drastically as some other individuals I know with MS. But given the complexity of these neurodegenerative diseases, how much interdisciplinary work is done? And maybe what breakthroughs are you most interested in or kind of looking at?
Tom Otis (20:43)
Yeah, I think in MS, MS is a disease, as you as you I'm sure you know, that is really a disease of the nervous system. So nerves are attacked, but they're attacked by the immune system. So it's both a neurology and an immunology disease. And the it's an autoimmune disease, right? So the immune system
antibodies are attacking the peripheral nerves, these cells that are glial cells that myelinate nerves and they're also centrally damaging nerves. And you know I think it's good to hear that the therapy, you know at least some of the therapies for your dad have worked. They tend to be right now pretty broad. I mean essentially
Most of them you could classify as immunosuppressant therapies, and those come with liabilities because you need your immune system. So immunosuppression is not, you know, can be dangerous and needs to be managed. When I was at Roche, they developed a drug called Acrevus, which was an antibody that actually helped reduce B cells, and that...
seems to be a very effective drug. I think it's one of the leading drugs now for MS. But the real, you know, I think the real challenge in MS now is there are therapies that can halt or slow the disease in many patients. It depends on the stage at which they begin their treatment. If the MS is too advanced, it can be much less affected, these therapies. So they talk about a relapsing remitting phase where the MS symptoms, you know, come and
And then there's a phase where the MS symptoms are kind of persistent and you don't get near perfectly better. And I think we need therapies, obviously, to allow the nervous system and myelin, these myelinating cells to repair themselves so that those who suffer from MS and are out of plateau, they can come back and regain function. And there are a lot of companies working on that.
Brendan Aylward (22:54)
That's it.
Brendan Aylward (23:00)
Yes, sir.
Tom Otis (23:02)
us.
Brendan Aylward (23:03)
Yeah, I know some of our clients with MS at the gym have tried the same medication that my dad has taken and it hasn't been effective for them. So it seems like it's a very individualized thing. But maybe on the topic of like pharma, do you think the last few years has made...
just like disseminating information and selling treatments. Has it made it harder with the whole landscape of COVID and maybe some distrust that people have? Just is the prevalence of these messages making it harder to develop drugs and disseminate material?
Tom Otis (23:42)
Yeah, I mean, and I think it's reflective of the larger world. You know, we're in a really fractured informational environment. It's easy for people to race ahead and to go and find what they consider to be relevant information, but it's a complicated world. You know, if I said to you, okay, you're going to take a trip somewhere and you're going to go by airplane.
you wouldn't think, well, I'm gonna go to the internet and learn how to fly a plane and just see if I can do it. And I would just say to people who, I mean, it's great for people to go to the internet and sort of say, all right, I'm gonna explore this topic. I, you know, I can make decisions on my own, but I would make the analogy to flying that plane, that, you know, there's a reason why, why experts and institutions and so on, why we rely on them.
And it's really good reason. And it's the same reason why you rely on someone who's trained as a pilot to fly the plane and you don't sit in the front seat and try it yourself, even if you might think I can do it. Right. So, but, you know, coming back to pharma, you know, the, I mean, look pharma and biotech, it's, it's a wonderful thing, but it's a, it's a system that is
It's expensive to develop drugs. They are too expensive. There's no question about that. That the fact that they're too expensive means that there's problems with access. There are heartbreaking decisions. In different countries deal with this in different ways. The US simply pays the highest bill, by the way, I could say, as an American living in London. In London, they have a whole system where they consider which drugs are value for money.
and they negotiate at a national level with former companies. And they get much lower prices for the same drugs. Sometimes they get them six months later, but if they're really important drugs, they get them. So, you know, it's, I mean, these are what I'll tell you what the CEO of Roche when I was there, I'll tell you what he said. And I think, you know, there are going to be differences of opinions and perhaps some of your audience will groan when they hear me say this, but he would make the point that.
Tom Otis (26:08)
When there is a transformative drug, like Roche's new drug for MS, which was a real step forward, there are some drugs for really devastating childhood diseases that have been close to what you might call cures, oncology drugs. There are drugs in this class. Once these drugs run their patent life, they are then in a way a kind of
there's a legacy left for humanity. Okay, and there are drugs that were developed and before the turn of the century that are still really important drugs. There are drugs, for example, immunosuppressant drugs, neuro steroids, et cetera, antibacterial drugs, epilepsy drugs, and those drugs have a high price. And then when they go off patent, there are many companies that can make them. And then we have them forever.
Okay, so that doesn't, you know, that doesn't free us from the ethical and moral quandary of, well, look, if my drug is $200,000 a year, you know, do I lose my house to be well and to avoid death? That's a big problem. But it is in the long run, I think. It is a system that has.
that has a happier ending than we sometimes think.
Brendan Aylward (27:40)
Yeah, it just takes long to develop. ALS in a taxi air condition set not everyone may be familiar with. Um.
Well, ALS is more public facing for sure. What role do you think the public awareness that's been generated from athletes like Pete Freights and Steve Gleason kind of has done for research? Does it trickle down to you? Does it just benefit the patients? Although your work benefits the patients. But I guess what role does public advocacy and awareness play in studying a rare disease or a condition like ALS?
Tom Otis (28:19)
I mean, I think it's pivotal. Patient groups can really be involved, not only having a front row seat to the development of medicines, but speaking both to scientists and to pharma and biotech companies. And we see this, I mean, I see this very much with the company that I work with now in the rare disease space where patient groups are absolutely essential.
and their voice is a really important part of the, hopefully the march towards a therapy. Also regulatory agencies, the Food and Drug Administration, the FDA definitely listens to patient groups. So there's political pressure, there's guidance that can be given to regulators about what aspects of diseases are most burdensome or where there is the most need for therapies.
And you know, and I think on the on the general patient awareness front, I'll just give an example, we we're working doing some work on Parkinson's disease. And Michael J. Fox's foundation is a major is really a pillar of Parkinson's therapy development and research, they've given out billions of dollars in grant funds. They are, you know, they really drive the field and they do it not only at the
the early kind of research stage, preclinical research stage, but also with promising companies to make sure that it's a really vibrant ecosystem. So, yeah, so I would say to those inclined, you can really make an impact. You know, it's not just the money, it's the voice.
Brendan Aylward (30:08)
Absolutely. Yeah, I like that. Is the work that you do patient facing at all or predominantly academic and research based?
Tom Otis (30:18)
It's kind of somewhere in between. So I, with the with this company, we are developing and hope that within a, and it's the website, if you want to go to the website is loriotx.com. The company is, we hope, a year and a half or so, about six months from declaring what we call a clinical candidate. And then about a year from
from possibly going into clinical trials. So we're kind of, you know, we're advanced in some senses, but still, you know, there's lots of work to do. And in that role, I go to scientific meetings and I meet with patient advocates. I meet with parents at these meetings. So I go at conferences you see and hear from people who are.
who are affected by the disease. In this case, the disease is so debilitating that the patients themselves have profound intellectual disabilities. So it's a little harder to interact with the patients, but I certainly hear about them and about their lives and what is important to them.
Brendan Aylward (31:34)
What have you learned about communicating with individuals who have terminal illness?
Tom Otis (31:39)
I mean, I think you, one needs to listen. So I try, it's hard for me, but I try to keep my tongue tied. Because every moment, if one doesn't have a disease oneself, or in a close family member, you just don't know. You don't know where the, you know, where all of the challenges are.
and where some of the joy is, if there is any joy. And I think it's so important to hear that firsthand, because not only, you know, as scientists, we think I have a theory of what causes the disease or what might mitigate the disease, but hearing what really matters to people.
what their challenges are, what they miss, what they'd like, if they had only a partial therapy, what would it do for them? That's really important, because it can orient you to think about those things.
Brendan Aylward (32:50)
Yeah, the field of medical humanities is really interesting to me, and just the research on how outcomes can be improved by the way you communicate and the way that medical professionals communicate with their patients is a really interesting idea to study for sure. But it kind of goes like in our...
Tom Otis (33:07)
Absolutely.
Brendan Aylward (33:10)
In the course that we teach to fitness professionals, we talk about the social model versus the medical model of disability. And obviously the medical model is essential for the work that you do. Everything is grounded in medicine, but there's also that social piece where sometimes a disability is just the product of either people not understanding or inaccessible societies. So it's cool to kind of have both things at play and having medical professionals that understand that the therapeutics and the medicine is essential, but that there is that patient.
and advocacy and understanding what they want to get out of therapy that is important. I like the intersection of those two.
Tom Otis (33:45)
Yeah.
And there's no question that therapy, I mean, so many therapies, and this is particularly true of neurological disorders, having the right neuro rehabilitation, or having the right, you know, tandem psychiatric treatment, along with, for example, a, you know, a pharmacological approach, those two in conjunction are much more powerful. Indeed, some drugs just won't work without having the second.
component. So that's a key, you know, there's a whole areas of research, as I'm sure you know, about how do you have the right rehabilitation component.
Brendan Aylward (34:27)
end of the two. Absolutely. Maybe on the topic of SCA, could you explain to the audience kind of what ataxia is and how it's being treated and how it kind of manifests on a day-to-day basis for individuals?
Tom Otis (34:43)
Yeah, so ataxias and SCAs would be genetic forms of ataxia. There are other ways that ataxia can result and in fact there's one that probably many people have the most direct experience with which is that alcohol causes ataxia. So the ataxia is just a medical term that means uncoordinated movement and it most it can be maybe most apparent
in someone's gait, the way that they walk, but it can also be apparent from the smoothness and the coordination of their movements. So, on a neurological exam, a neurologist might ask someone to walk down a hallway and back, and a patient that suffers from ataxia might have a wider stance, and they might, you know, have trouble with balance.
During walking they might even need assistance With balance so balance is a key part of this other features that a neurologist might look at are Eye movements so they might ask, you know, put their finger up and ask you to look to follow their finger with your eyes and they're looking to see can you do that smoothly and Particularly when you get to the edge of your gaze is the gaze fixed
or do the eyes beat, you know, you can't hold a gaze and that's called nystagmus. That's a classic ataxia sign. Alternating movements, the neurologist might ask, you know, someone to do this repeatedly or to touch their nose and the finger of the neurologist and ataxia patients will pass point and they might have a tremor when they're moving. So they might, you know, not be able to hit their nose.
So all of these things, and then I mentioned motor learning earlier, you know, any kind of coordination, coordinated movement like in sport or in music where someone through practice will learn to make more precise movements, that is degraded in a patient with ataxia.
Brendan Aylward (37:06)
We see a taxic CP as one classification of cerebral palsy as well, that we will sometimes observe in clients. But what is, I guess, what is the current treatment for ataxias? Is it different between SEA and other forms? Is there a genetic component? Is there a nurture component?
Tom Otis (37:28)
Yeah, I mean, most ataxia, so ataxia, the spinocerebellar ataxias and also the what would call idiopathic ataxias, so cerebral palsy, ataxia is a nervous system insult from early life. There are chemical sort of permanent forms of ataxia. There are autoimmune forms of ataxia.
In all of these cases, the treatment right now is unfortunately largely symptomatic. So neurologists can prescribe medicines to make these things better, to reduce tremor a bit, to reduce other symptoms of ataxia. But particularly in the area of the genetic ataxias, there are many
many programs now where the genes are being directly targeted and they are gain of negative function. So they're, you know, a gene that's doing something untoward. And so blocking this gene is technically fairly straightforward, I'd say now. And the only challenge is can you develop a therapeutic that's safe? And obviously that's effective that blocks the gene effectively.
block it too much in some cases. And there are many clinical trials now proceeding. So I'm hopeful. I am very hopeful that a lot of this stuff will, within the next five years, will see some drugs approved. And hopefully, they'll have really high effectiveness, not just a little bit.
Brendan Aylward (39:14)
Yeah. For individuals that might be interested in pursuing a career in researching, like neurodegenerative diseases, what would you recommend or what is your advice?
Tom Otis (39:27)
Well, and I'm not just saying this because I grew up there and you live near there, but you could go to Boston. Boston, there's some good places to study in Boston, certainly. So I think there are so many ways to make an impact and those can be, of course, to study a research area, like neuroscience, or to study medicine, medical aspects of neuroscience that might be neurology
or psychiatry. So those would be traditional ways, but I think patient advocacy, patient care aspects, nursing, rehabilitative care, I mean, these are all areas where a huge impact can be made. And so I think there's clearly plenty of work to do.
Pediatrics.
Brendan Aylward (40:26)
What brought you to London if there's so many good opportunities here in Massachusetts?
Tom Otis (40:30)
Yeah, this is like, this is like what my relatives in Boston will say. But it is a fair question. I, you know, it was a meandering path. So, I had a faculty position after I finished my PhD and did a little bit of extra study, I had a faculty position in Los Angeles. So I worked at UCLA for many years., and then.
Brendan Aylward (40:35)
Yes!
Tom Otis (40:56)
you know, really jobs and challenging jobs that I thought would be good for me. Drew me first to Switzerland, to Basel. So I went from academia and I went to work at this drug company, Roche, which was really thrilling. It was exciting to see how medicines get made at scale in a big company like that. And then I had an opportunity to come to London.
which is back a bit more in academics, but also with the freedom to do, to work, to develop this company. And London's been great. I mean, I, it's nice to live in different places, you know, I think, even though.
Brendan Aylward (41:39)
I can't relate to that as someone who rarely leaves Massachusetts. Not sure I've left Lancaster in a couple of years, but no, that's awesome. A lot of our audience is in the health and fitness space. Do you see any overlap in terms of what you do and maybe what someone can do?
Tom Otis (41:41)
Yeah, you know, Boston's the best. Wonderful.
Brendan Aylward (42:07)
to improve, I guess, their health and fitness and just in terms of recreation.
Tom Otis (42:15)
Yeah, well, I mean it is an established fact and I'm sure you know most of your audience probably knows this and feels this that physical fitness throughout life Is is the single most important thing you can do To stave off disease and that's true of neurological disease and it's certainly true of cardiovascular disease You know other big areas and metabolic diseases, but in the neurological space area
You know, in terms of Neurological area in terms of dementia, age related dementia. If someone's active, it's a major factor in the plot and the plus column in terms of staving off cognitive decline. So absolutely keeping fit. And then there's the mental aspect of it. You know, for most people who are physically fit, I don't know if I'm physically fit, but I would certainly say about myself that physical
activity and even being, you know, walking around being whatever your choice of physical activity is, but it can be more strenuous or less strenuous. It had, it bears mental health dividends where you're clearer, you're able to deal with stress in a better way. And those things obviously also are really crucial for health.
Brendan Aylward (43:43)
With ALS being a decline of physical function, is there, are you familiar with anything that correlates activity levels and?
the progression of the disease, not to imply that you can reverse it in any way, just by being more active after the diagnosis. But has that been shown to prolong it? Or I was even like, I didn't have a thorough conversation about it, but I remember talking to a muscular dystrophy researcher a couple years back, and he said in some cases they advise against exercise because it almost expedites the decline of motor ability.
Tom Otis (44:17)
Hmm
Brendan Aylward (44:24)
research kind of correlating physical activity and the progression of the disease.
Tom Otis (44:29)
I mean, I don't I don't I'm not an expert in that area of ALS fields and muscular dystrophy is a very specific disease. So I think there is probably specific aspects I think in general, you know, within reason, and both for mental and physical benefits, having some activity that is where there's, you know, there's, there's a
Maybe there's, in the case of a severe disease, there's guidance from a rehabilitative therapy specialist. This is a positive thing in most circumstances. And, but of course, for very severe and rapidly progressing, they use the word progressing for these diseases, which always sounds wrongheaded to me, but anyway, they call it rapidly progressing diseases.
Tom Otis (45:31)
they're not necessarily going to slow the disease. And I think that also, that's one of the many tragedies of the disease in that many of these neurodegenerative diseases and diseases of later life, the loss of mobility is really a very negative aspect of the disease and it can make it so that it's harder to...
to stay healthy in other aspects.
Brendan Aylward (46:03)
Yeah, the loss of independences, I would imagine, incredibly frustrating. What are you most excited to work on over the next, maybe three or five years?
Tom Otis (46:13)
Well, you know, the current project on genetic pediatric epilepsies is really invigorating. So I'm hoping that we can make real progress and bring something into the clinic that has the potential to be a medicine. And it's, you know, I think our ideas, they're, they're pretty bold. So I'm excited about that.
I'm excited as a kind of bystander, a well-educated bystander to see some of these other programs in ALS and spinocerebellar ataxia, Alzheimer's disease, these therapy developments for these truly terrible neurological diseases, they're advancing. And I'm really hopeful that we might have an inflection point where there's a new therapy and it's really clearly a winning drug. It would be so satisfying for science and for the patients and everything to see that.
Brendan Aylward (47:17)
Absolutely. Yeah, that's a good, hopeful kind of way to maybe wrap up some of this in a topic that is incredibly challenging and can be disheartening. I would imagine working with patients that have to deal with these conditions. Hopefully there are a lot of progress that's made over the next few years in how we treat them.
So Tom, thank you for sharing your expertise and doing my best to keep up with the topics that you're covering. But if anyone is interested in kind of learning more about the work that you do, is there a specific place that they can find you or resources that you would direct them to?
Tom Otis (48:03)
Yeah, I mean, I'm, as you said, at the University College in London. And so you can find me you know, you can find me on the web by my email address is t.otis@ucl.ac.uk, And yeah, I mean, who knows, maybe we'll see each other at a conference or some other event.
Or in Massachusetts?
Brendan Aylward (48:34)
Yeah, yeah, absolutely. Next time you come back up to Mass, if you visit Dennis or anyone, you'll have to stop by the gym and see what he's working on with us. But we can put that stuff in the show notes here, your email, and then the companies you're working with. So Tom, thanks again. I really enjoyed a conversation and hope that the audience finds value in it as well.
Tom Otis (48:56)
Thanks so much. It was really a pleasure from my end as well.