#320 Genetics in Neuromuscular Disorders: Diagnosis and Treatment with Dr. Robert Bucelli
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When it comes to your health, knowledge is power. I've always believed that the more we understand about our bodies, the better decisions we can make, whether it's about the food we eat, the exercise we choose, or how we plan for the future. But traditional healthcare often feels reactive and not proactive. That's why I'm so excited about 23andMe Plus Total Health, a longevity platform that puts you in the driver's seat of your health journey.

With 23andMe plus Total Health, you get advanced genetic screening, giving you insights into your potential future risks, and comprehensive blood testing throughout the year to track how your health is changing. It's a level of personalized care that goes far beyond the one-size-fits-all healthcare system that unfortunately we're used to. Advocate for your health today. Go to 23andMe.com slash DNA Today to receive 10% off your Total Health membership.

Again, that's 23andMe.com slash DNA Today. You can also find this link at DNAToday.com. Take charge of your future health with 23andMe Plus Total Health because your health deserves a personalized approach. How is it that we find ourselves surrounded by such complexity, such elegance? The genes of you and me. The genes of you.

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Hi, you're listening to DNA Today, a multi-award winning podcast and radio show where we discover new advances in the world of genetics. From genetic technology like CRISPR to rare diseases to new research. For over a decade, DNA Today has brought you the voices of leaders in genetics in over 200 episodes. For the past three years, DNA Today has won the People's Choice Best Science and Medicine Podcast Award. I'm Kira Dineen. I'm a certified genetic counselor and your host. ♪

You may not know that DNA Today isn't the only podcast I produce. I actually have fun collaborating with other teams like the Journal of Genetic Counseling's new podcast, DNA Dialogues, and Lorem's Patient Empowerment Program, the Phenotip Speaker Series, and relevant to this episode, I'm the executive producer of It Happened to Me, which explores rare diseases and medical challenges. This week, the show released its 50th episode.

So a huge congratulations to It Happened to Me for reaching this landmark milestone episode and also coincided with wrapping its second year of episodes. So to celebrate both of these milestones, I am sharing this special interview on DNA Today's feed.

So this episode of It Happened to Me features Dr. Robert Buccelli, who explores neuromuscular neurology, including the role of genetics in diagnosing and treating neuromuscular disorders, which is why I also thought it was relevant and you would enjoy this episode because there's so much of a focus of genetics in the episode that as I was the producer with my mic and video turned off for this, I was learning so much.

Over the last two years and 50 episodes, It Happened to Me co-hosts Kathy Gildenhorn and Beth Glassman have drawn on their own health challenges as they interview these patient advocates and medical experts who share stories and knowledge to help you listeners succeed in the face of difficult health obstacles. Again, I hope you learn as much as I did in this interview. ♪

Thank you.

The real question is how we adapt. That's the focus of It Happened to Me, which wants to help you overcome limitations and live a full and satisfying life. Drawing on their own health challenges, co-hosts Kathy Gildenhorn and Beth Glassman interview guests who share stories and research to help you succeed in the face of difficult health obstacles. It Happened to Me, I'm not alone, and neither are you.

Joining us to discuss neuromuscular neurology is Dr. Robert Buccelli, and I must disclose that I am a huge fan of Dr. Buccelli's as he is my personal muscular neurologist. For over a decade, Dr. Buccelli has been a practicing neurologist at the Washington University Neuromuscular Clinic.

He's a professor of neurology, pathology, and immunology at the Washington University School of Medicine in St. Louis, where he serves as the site principal investigator on several clinical studies relating to ALS.

Dr. Buccelli is also co-director of the Washington University Neuromuscular Clinical Laboratory and co-director of the Washington University ALS Center.

After graduating summa cum laude from Canseas College in Buffalo, New York, with a degree in biology, Dr. Buccelli went on to receive his medical degree and PhD from the State University of New York at Buffalo as part of the Medical Scientist Training Program. Dr. Buccelli is an expert in diagnosing and treating diseases

neuromuscular disorders, including ALS. His skill in delivering drugs to the fluid surrounding the spinal cord has enabled Dr. Buccelli and the Washington University's leadership team in trials using ASOs to turn off the production of harmful genes that cause ALS. Welcome, Dr. Buccelli.

Thanks very much. Thank you, Dr. Buccelli. Now, let's start at the beginning.

Can you provide our audience with an overview of what neuromuscular neurology entails and who is typically affected by it? Sure. So the way that I typically will describe neuromuscular neurology to folks that aren't familiar with it is medicine is progressively more and more subspecialized and within the field of neurology, you

could break it down to 10 to 15 different subspecialties within our field and there's um

The majority of those specialties are devoted towards disorders of the brain and to some degree the spinal cord. And they have double digit numbers of specialties devoted towards those portions of the nervous system. And there's only one that's devoted to everything else that's outside the brain and spinal cord, meaning the nerves, the nerve muscle communication point called the neuromuscular junction, as well as the muscle.

So neuromuscular neurology deals with all of that, everything other than the brain and spinal cord. Now, some of the disorders that you're alluding to, like LS, obviously that kind of spills over and doesn't exactly obey those boundaries. But for the most part, we're dealing with everything outside the brain and spinal cord.

Now, are there typical patient groups that are affected by neuromuscular neurology and its issues? Yeah. So, you know, certainly ALS is primarily followed by neuromuscular specialists, even though it, again, doesn't exactly fit that rule I applied, but

Peripheral nervous system disorder, so very common one. People with polyneuropathy or peripheral neuropathy, folks with muscle diseases, myopathy, myasthenia gravis is a common one of the communication point between the nerve and the muscle.

And then those are kind of very common categorical associations with neuromuscular neurology. And then there's a litany of other disorders that fall in underneath those, what we call localizations or categories of disease, be it the nerve, the nerve muscle junction or the muscle. And are individuals with rare or genetic disorders and diseases more prone to experiencing neuromuscular neuropath?

issues? Or is it a standalone medical challenge that anyone can face? I would say that, you know, certainly we take care of patients with both hereditary or genetically determined disorders in the classic sense of something being quote unquote genetic. We also, you know, these same categories I was just alluding to can be due to acquired disorders that aren't necessarily genetic. I would say that within the field of neurology, probably the

The subspecialty within neurology that is the furthest along or has the deepest kind of genetics associated with it is neuromuscular disorders.

Mainly because of, again, the breadth of what's covered, as I was alluding to, there's so many things that fall within the scope of neuromuscular disease, but also the sheer number of disorders that fall within that. So I'd say of all of the fields within neurology that end up dealing with clinical genetics, neuromuscular is probably at the top. Right.

I know personally that I have had tremendous difficulty other than I'm so lucky to have found you as a neuromuscular neurologist. But it has been so hard for me to find anyone else with that specialty. Is it rare that neurologists choose this specialty or am I looking in the wrong place? What's going on here?

That's a fantastic question. I would say that in general, when you look at the U.S., neurology in general is a field that's very much in demand. There's not enough neurologists spread across this country, certainly in certain areas with

higher populations, the density of neurologists may be a bit higher. But when you look across the entire nation, neurologists are certainly at a shortage. And then when you look within the field of neurology, there is absolutely a paucity of neuromuscular specialists, even within, you know, the field of neurology, a lot of people shy away from or kind of look away from the peripheral nervous system, I'd often find there is the need and a lot of people

Well, those of us that do it know how great it is and how much we love it. Yeah. There's a lot. There are a number of centers where there may not be, even at large urban areas, there might not be a single neuromuscular provider in that metropolitan area. My goodness. Wow. Doctor, do you treat MS? Yes.

No. So MS is one of those disorders that primarily falls. There's actually centers that have like entire groups solely devoted towards multiple sclerosis or it's kind of similar disorders, but that's a, that's a disorder of the brain and spinal cord. So that's another one of the disorders that are usually taken care of by neuroimmunologists or MS specialists.

Boy, this is a very complicated field, doctor. So can I ask you, so how do you diagnose and treat a patient when they come to you? How do you determine what they have? One of the beauties of our specialty and what we still do even present day in 2024, despite the fact that technologies are what they are and

You know, you have access that, you know, your hand to very powerful things like genome sequencing and all these imaging studies and fancy blood tests, everything like that. One of the beauties of our specialty is that so much of it still rides on.

The history of talking to the patient and then examining them. We're still very much reliant on that aspect of the evaluation. The reason why that is still so integral to us is kind of what I was alluding to earlier. There's so many different things that we end up taking care of and so many different types of disorders that fall within the spectrum of neuromuscular disorders.

That we really do use our history of what the patient's experiencing along with what we see at the bedside exam to then guide next steps because there's a huge array of different diagnostic approaches that one can take nowadays.

I would say that one of the things that's a bit unique about neuromuscular that we definitely use and is a tool that isn't as commonly available or something like it in other forms of neurology is something called electromyography and nerve conduction study or EMG nerve conduction study testing, which is something that...

This is what Kathy... This is what I've had a couple times. The beauty of that, and again, it's a technology that's been around for a long time and progressively fine-tuned over the years, but

It's this really beautiful way to kind of almost make that bedside examination that we do or we're examining a patient. It makes that exam that much more sensitive. And then it allows us, if we see a patient on our examination and we can detect weakness, it can tell us where that weakness might be coming from. Is that coming from...

The brain and spinal cord, is it coming from the nerve roots? Is it coming from the peripheral nerves, the muscle? And so that test is oftentimes something that's oftentimes paired with our clinical assessment to help narrow down what we might be dealing with and guide treatment. And then to some degree can be used for tracking disease activity in some specific disorders.

I'm glad to know that within this specialty, that that

patient-doctor relationship still exists. We hear so much about AI, and it seems as though machines are going to take over. I'm glad to know that the doctor is still very much present with the patient, and that dialogue makes a difference. It sounds like what you're saying. Yeah, it really is integral to what we do. I mean, for neurologists, and we teach, you know, this is something we'll teach neurologists in training and medical students, is that

A neurologist without a good history, you know, oftentimes if the person can't provide the history themselves, we'll have to go to a collateral source. But a neurologist without a history is kind of, you know, guiding the, they're basically walking blind. They don't know where they're going with things. And they really anchor a lot of what they do to that history. It completely shapes what we do when we examine a patient, shapes what we think is going to be of health.

help when we're pursuing diagnostic testing and certainly is critical to making a diagnosis. So it's still very much in 2024 integral to the practice. Looking to jumpstart your career as a genetic assistant? These essential roles involve patient communication, data management, genetic testing coordination, and admin tasks, making proper training a must.

The Genetic Assistant Online Training Program at Johns Hopkins University School of Medicine is a top choice. DNA Today listeners rave about how this course boosted their genetic counseling skills and prepared them for grad school. The spring cohort starts soon on January 27, so apply now before it's too late. The program includes two 10-week instructor-led courses.

Armed with a basic science background, you'll earn a certificate from the Johns Hopkins School of Medicine upon completion. You'll also gain practical skills and insights from leading instructors that will give you a competitive edge in genetic counseling and related fields. Learn more at dnapodcast.com slash sponsors or simply search Genetic Assistant Online Training Program Johns Hopkins.

Ask you something. Is there something that we as patients can do to in a preventative way to I don't want you to take offense, but so we don't have to see you doctor. And I take a supplement. Can I change my diet? Can I exercise? Can I take vitamins? Do any of these things work?

Yeah, no, I think that those, it's a great question. I think, you know, prevention is the best medicine. So it's a really, really great question. I would say that, again, getting back to kind of the breadth of neuromuscular disorders, you know, depending if you're a lumper or a splitter, our field has literally thousands of diagnoses that fall underneath the umbrella of neuromuscular disease. And so, you know,

Depending on the specific disorder, there absolutely are certain things that can be extremely helpful. If we take, you know, one of the more common disorders that fall under a muscular disease like peripheral neuropathy, one of the leading causes of peripheral neuropathy, particularly in the United States, are things like metabolic syndrome and diabetes. And there's really good evidence to say that, you know,

All the things that you hear about from your physician in terms of diet and exercise and all these things, changing one's lifestyle, diet, all these things. There's actually good objective evidence that you can actually modify and actually patients with diabetic neuropathy can actually have objective improvement if they're able to get some of these factors under control, tighten up their blood sugar control,

lose weight, deal with the other aspects of metabolic syndrome. All of these things have been shown to really make a huge impact on that particular disorder.

And then, you know, there's tons of other examples. There's patients that have certain forms of what we call metabolic myopathies, where by using certain supplements, they can prevent themselves from developing episodes of severe muscle weakness. And so, again, it gets back to, you know, really having a, we spend so much time up front with our assessment of patients to really make sure we have the diagnosis right, because

Because it influences everything. And then, you know, one thing I'll just mention about since the questions about neuromuscular disorders is we're still very much in our field in that position where there's a ton of things we don't know. And so there are a lot of patients where we don't have an answer. We might not know exactly what's going on. And we still are...

And 2024, still in a position where another cornerstone of neurology and what we do is sometimes we're following patients and with more time, we're able to get more clarity as we get smarter, we're able to come up with better answers and achieve diagnoses for patients and provide them better care.

But there's still a lot of things in our field that we don't know. We're still learning a lot day by day. So yeah, I can't give you a more specific answer to that question just because it's, you know, each disorder is going to have a different answer.

Wow. But taking good care of yourself is still the best medicine. Absolutely. Do what you what you have domain and control over. And I think there's there's a lot to be said for that. No doubt.

Now, in terms of managing these neuropathic conditions, do you recommend physical therapy or occupational therapy as part of the treatment plan? Or are these therapies primarily aimed at minimizing issues or teaching individuals how to adapt to their new realities?

Yeah, no, I think that that's another great question. And what I would say is, you know, as a general kind of umbrella response, our field absolutely works hand in hand with physical therapy, occupational therapy, other therapy services.

And it's integral to the kind of standard of care for so many of the disorders that we take care of. You know, our clinic has and we partner with and have wonderful physical therapists that have always been part of our group at WashU and are present in our clinics and are great partners in providing care. I would say that depending on the disorder, there's varying levels of evidence. A general rule of thumb that will go off is

you know, in terms of things like exercise, physical therapy in general, there's very few, if any disorders for which there's not going to be support for engaging these types of things. And the right, you know, like any field, like we were talking about with specialization, you know, there's certain physical therapists that are going to have a lot more familiarity with neuromuscular conditions and the specific therapeutic interventions that would be of benefit

Again, as I was alluding to, we have a great group here at WashU and a lot of great experience and historical kind of representation for physiotherapy within neuromuscular diseases here. And there's other great centers around the country. Without a doubt, you know, some of that's going to tie into the fact that you're dealing with disorders that

Unfortunately, the natural history or what you're expecting with those is progression and people will, you're expecting that patients will get worse with the disorders present day. And so some of that can be helping the patient navigate how they're going to live with that disorder and

adapting to it and all of this. And then there's other disorders for which, you know, we have good therapeutics or there are therapeutics in development or, you know, we're on the verge of something kind of important. So for those specific disorders, there can be a very nice synergistic effect of physical therapy where timed out the right time, you know, it can actually help hasten and improve the ultimate outcome and recovery. And so,

Again, depending on the disorder you're dealing with, you know, and the group you're working with, there's absolutely a role for it. Wow. Now, are there some common symptoms or indicators that someone might be experiencing neuromuscular issues? Yeah. So some common things, not specific to, again, every disorder, but oftentimes patients with neuromuscular disease will...

develop issues with weakness, problems with mobility. They can have problems with sensation, pain, balance, mobility. Depending on the disorder you're talking about, it can also involve things like speaking, swallowing, emotivity, breathing. Less common, but sometimes the case, and again, I was alluding to the fact that our specialty in neurology doesn't deal as much with brain and spinal cord disorders. So

our field is going to end up dealing a lot less with like headaches or memory and thinking problems in general. Now, there's always exceptions to that. And some patients with certain forms of neuromuscular disease will be at risk of developing those types of things as well.

But in general, those first things that I mentioned are going to be the more common types of symptoms that are going to lead a patient to end up to coming to see us. And sometimes, you know, there are other areas of the nervous system like the spinal cord where people can

You know, they see their internist, they're having sensory changes in their feet or problems walking or their legs are weak and they're like, oh, well, this must be neuropathy. And so they send them to see us. And it's when we do that examination that we can actually realize, well, this actually looks like it's probably more of a spinal cord issue. And then that might be a different neurologist. But for the most part, those initial symptoms I mentioned are going to be the kind of cornerstone common things that are going to lead somebody, whether it's the patient or

or a non-neurologist to say this may be a neuromuscular issue. So the adage is you should tell someone what you're feeling. Yeah, absolutely. I think a neurologist is key. One of the cornerstones of what we do is really listening to what the patient's experiencing. And again, I would teach this with our trainees and students is

really to get the best sense as to what, you know, oftentimes, you know, we're in clinic and we'll ask a patient, you know, what brings you to see us? What's going on? And it's very common, particularly present day, people will oftentimes say, well, I went and saw this doctor and they told me I had this. And it's like, well, we don't want to know what, you know, we don't want to know what you're told yet, but like, tell me what it is that, you know, your day to day, your

activities as you go through your day what is it that's not right and by hearing well I'm having problems you know something as simple as one individual having a problem getting up and down off the toilet versus somebody else just having problems when they change surfaces is how they're walking that could be a clue to a neurologist where a person's weakness might be or where you're going to think more about examining when you do that your examination on that patient so

We want to know kind of what it is that you're experiencing because that's going to help us kind of narrow down how we cater our evaluation and diagnostic evaluation. Are there special risk factors that predispose someone to having these issues? Yeah. So, you know, certainly...

common one I alluded to. So metabolic syndrome, diabetes, definitely one of the more common causes of peripheral neuropathy and certainly, you know, an issue in the U.S. and other developed countries. I would say that really it depends on which category you're talking about. There are, as we were alluding to earlier, a number of hereditary disorders or genetically determined disorders that are kind of at the forefront of neuromuscular medicine. And so

A lot of those disorders are what we'll call dominant, meaning, you know, if you have a family member like a parent with this disorder, there's general 50-50 risk of you having inherited risk to develop that disorder. And so there is genetic risk factors for certain disorders that are very common in neuromuscular disorders.

I was just going to ask you that, doctor, about the role of genetics and the role of a genetic counselor and genetic testing would play in your diagnostic journey. Yeah, absolutely. And again, probably certainly here at our center, and I would say it's probably comparable to other centers, we're probably, and I don't have to say probably, we are the group at our center within neurology that does the most clinical genetics.

We have a genetic counselor that now works with our group at WashU. And then for a lot of our clinical trials, we have genetic counselors that are part of the research team and the investigator team. And we absolutely, nowadays, it's very common, particularly with there being meaningful therapeutics available for folks with different forms of hereditary neuromuscular disease,

You know, diagnosis, as I was alluding to earlier, is key. And so the earlier you have a diagnosis, the earlier you can get on meaningful therapeutics.

And so because of that, for a number of reasons, there's a lot of widely available and easily accessible genetic testing. Genetic testing is something that, you know, has gotten just over the course of my time in medicine is, you know, the cost of it and its availability is just totally different than it was when I started training. It used to be...

We had to do like everything to prove we wanted to do a one gene test by something called Sanger sequencing, which was long and laborious and very resource intensive. And nowadays with the technology being what it is, the cost of what it used to be to do that one gene test is about the same as it is now to do like genome sequencing. And so, yeah,

That's a double-edged sword in that, you know, there's a lot more data that you have to be able to navigate and deal with because you're going to find a lot of things that, you know, you might not have been able to do the genetic testing. And so that's where things like good genetic counselors, a deeper understanding of what the testing is that you're doing, its limitations are.

And then also like having partners. So we have really great collaborations and partnership with folks in clinical genetics here. So we know kind of what we know, but once we get outside the scope of things that fall outside our level of comfort or expertise, it is good to have additional experts available that can help us out.

Wow. Now I've got to ask for individuals who are already diagnosed with neuromuscular issues, what type of ongoing support or management strategies are typically available and are recommended? Yeah. So I'd say that, again, depending on the disorders, we can use certain examples. So some of the

really fantastic resources available for folks with different forms of neuromuscular disease. There's the Muscular Dystrophy Association, the ALS Association. These are great groups that provide a number of important, not only supportive measures, but a community for patients dealing with these disorders. I would say that, you know, we've been able to

you know, locally, we've been able to find that patients, some patients more than others, have actually wanted to provide that support for others going through what they've dealt with, particularly when we're dealing with ultra rare diseases. I've taken care of patients that have said, like, you know, it was really tough to go through what I've gone through, given the lack of community with the fact that my disease is very rare and novel and

Not surprisingly, with how selfless some patients are, they've said, you know, I'm happy to, you know, speak with anybody that might be dealing with this or that you do end up identifying. And a lot of kind of really amazing efforts have come of that, of kind of building one's own community.

I would say that, you know, between that and, you know, good patient-physician relationship and, you know, being taken care of at a center that, you know, has familiarity with the disorder and what's out there, I'd say that there's been really amazing. I've had, you know,

over the last 10 years or so, been able to appreciate the value that patients get from the community kind of experience and the support that they get out of participating in clinical studies. You know, I've had a number of patients that have participated in trials, and they've told us that one of their main reasons in the end that they continue to come to participate in studies is that kind of

The community that they form in doing so by coming and participating, the nurses that they see every couple weeks or months, and the study team that they end up getting to know, it provides this additional kind of support.

source of emotional, psychological support for some patients. So I'm sure there's probably others that I'm not thinking of, but those are some of the ones that are commonly utilized. That's really interesting. It's so nice. And you know, it's exactly why we started this podcast, was to build community and to make people feel

anyone with rare diseases or medical challenge is almost everyone, that I'm not alone and neither are you. And it's so nice to hear what you say from the medical doctor perspective, just seeing the need that patients have, because we've seen so many patients that have been on the show really thrive

by advocacy, and by setting up foundations where there is a void, and just the type of activism and advocacy that you're talking about. And it's so wonderful to hear you just

Speak of it that way. Thank you. And Kathy, we've also found that support groups, doctor, that you spoke about have also been extremely helpful for patients. So it's so interesting that as a provider, you are seeing this from your patients and the benefit. Absolutely.

I think absolutely. I think medicine is so rushed now. And like, even we're very privileged being in an academic center where we get like a whole hour budgeted to spend with a new patient. Like it's still not enough time, right? Like to actually, to really get to know how a disorder impacts a patient and all that goes into it beyond just like the very brief snippet you get when they come to see you every few months or once a year.

There's so much more to a disorder than that. And so I think there's so much value that can be offered. Sometimes, and this is definitely the case, the folks in our clinic, like again, I think one of the reasons patients oftentimes benefit from participating in clinical studies and trials is

is of course, you know, we hope that the trial and the therapeutic intervention being tested will benefit them, but they have a lot more contact, a lot more time with the study team. There's a lot more, you know, you're not limited by that 30, 60 minute clinic visit. There's a lot more that can happen during that time to really understand what's going on. Maybe a longer conversation is what really leads somebody to understand a little better what somebody's dealing with. So I think that

These formats and these venues oftentimes can be, depending on the disorder you're talking about, of more value to just going and seeing the doctor every three, six months, whatever it might be. So much of what we do in neuromuscular is multidisciplinary. And I stand by the fact that

If we take ALS as an example, the physical therapist and the speech therapist and the respiratory folks and our social worker and our dietician, they do so much more for those patients than I do. And it's just so, so important. And oftentimes it's resources and time that are the greatest limiting factor.

When it comes to your health, knowledge is power. I've always believed that the more we understand about our bodies, the better decisions we can make, whether it's about the food we eat, the exercise we choose, or how we plan for the future. But traditional health care often feels reactive and not proactive. That's why I'm so excited about 23andMe Plus Total Health, a longevity platform that puts you in the driver's seat of your health journey.

With 23andMe plus Total Health, you get advanced genetic screening, giving you insights into your potential future risks, and comprehensive blood testing throughout the year to track how your health is changing. It's a level of personalized care that goes far beyond the one-size-fits-all healthcare system that unfortunately we're used to. Advocate for your health today. Go to 23andMe.com slash DNA Today to receive 10% off your Total Health membership.

Again, that's 23andMe.com slash DNA Today. You can also find this link at DNAToday.com. Take charge of your future health with 23andMe Plus Total Health because your health deserves a personalized approach.

Well, I've got to ask you one other question. And how do neuromuscular neurological issues impact daily life and functioning from what you see? And what strategies can individuals use to cope with all these challenges?

Yeah, so I think, you know, depending on the disorder, it's going to vary quite a bit. For disorders that affect motor function and affect strength, it can be very, very debilitating and lead to the need for a lot of modifications to one's home. People sometimes have to move to a single level home. They have to completely redo their bathroom, redo their bedroom.

They might need beds that allow them to get up and out of bed. They might need horror lifts. Oftentimes what we're doing is partnering with occupational therapists that can go into patients' homes and really look at how they live their life. Like, how are they getting through their days, what they need to do, and then they can make recommendations and

Again, this is another area that can be very resource intensive and we try and do what we can. And is it generally evolving so that if someone comes in and were to make that assessment, it would change? Yeah, it can. And so, you know, again, that's the idea of working with folks that have some familiarity with what the trajectory, natural history of these things might be so that.

They don't have somebody completely overhaul their home to do something, and then five years later, it's a moving target. It could be something as straightforward as for folks that have loss of sensation in their lower limbs, something as simple as a grab bar in the shower could be a huge impact and help them from having a very high-risk fall experience.

in a dangerous environment like the shower. So I call them small things. They're actually very big things, but things like that are sometimes things we can pick up in clinic. But again, it's oftentimes quite helpful to be able to partner with folks that can really see patients

in their home living environment and make recommendations to us to make sure that they can, again, live their life as independent as possible and acknowledge that, as you were alluding to, that things change and it's a bit of a moving target. Dr. Pichelli, you alluded to clinical trials. Tell us about some developments that you find personally exciting.

what's on the horizon? Yeah. So the thing that's been really exciting in recent years here, so our center, you know, we're the, if I talk about ALS, so within the world of ALS, you know, we've been involved in a number of different programs across the whole spectrum of the field of ALS. One area in particular that we've been very involved in is with the use of antisense oligonucleotides. And one of the reasons for that is the

co-director and really I'm a co-director of the ALS Center, but the real director of the ALS Center at WashU, I would say is Tim Miller. He's somebody that's really, he's a physician scientist, a brilliant guy that's devoted his career towards this aspect of medicine, this really amazing biology that allows us to kind of knock down the products of genes via antisense oligonucleotide therapy. And so

He's been working in the ALS world for a long time and one of the drugs that he helped develop in his lab

eventually made it through development and was just FDA approved. Oh, that's great. A year and a half ago. And that, I think if I'm not messing that up, I think it's a year and a half ago now, time flies. But the bottom line is this drug has really changed the way that a number of us have thought about that particular disorder. And it's probably just the first of a number of drugs in that category of drugs that will really make a big impact on that disorder for which

you know, is long overdue for some big wins. Yeah. How do socioeconomic factors or access to health care services generally affect the diagnosis and the treatment of neuromuscular neuropathic conditions?

Yeah, I would say that it's a really important question. I would say it's not unique to our field. I'd say that as we were talking about, you know, access to neurologists, including neuromuscular doctors has been shown through good evidence that certain socioeconomic factors, location, all of these things will definitely lead towards certain populations not having access to the resources, whether it be neuromuscular or other forms of neurology. And that includes patients

One of our former trainees did a nice study showing that even access and pursuit of genetic testing through the population locally within neurologic disease was very different based off socioeconomic status and other variables.

And I think that it's not unique to our field. I'd say our field follows suit with others that have shown that, you know, certain groups are definitely being missed and not having the same access to care that others are. And so,

I think, you know, there's definitely been more awareness of this and a concerted effort towards strategies to address that gap. But it's no doubt nowhere near where it needs to be. Where it needs to be. Now, are there any emerging technologies or innovative approaches that really hold promise for improving the management of neuromuscular neurology issues? Yeah, so in terms of...

We were talking about genetic disorders or hereditary disorders. I think the therapies like S-based therapies, which is not quite antisense, but targets the same kind of part of the pathways, a lot of gene products moving down to its protein. ASOs have been encouraging more and more. And this is now just recently with this technology being used to help patients with sickle cell disease.

Things like actual gene editing. Yeah, that's what I need.

There's all these challenges associated with that. But with the breakthroughs that have happened with sickle cell, you have to imagine that it's not far off before those technologies would actually be able to be applied to our field in neurology. We have had, particularly in the pediatric neuromuscular world, some just incredible breakthroughs and home runs with using vector-based true gene therapy, where genes that, you know, a lot of what we've talked about so far are knocking down toxic products. Right.

A lot of disorders are due to the absence of a needed protein. And so these vector-based genetic therapies, like an example being the therapy that was approved a few years ago for spinal muscular atrophy, which is a pediatric onset motor neuron disease in the neuromuscular world, that intervention has just completely changed the face of that disorder. And so

Again, that's not the only disorder for which gene therapy is truly available now, but more and more, you know, looking towards using these types of therapies for things like muscular dystrophy and other neuromuscular disorders is certainly on the horizon. Very exciting. Yeah. So, Dr. Closing, what parting advice would you give

to patients and to our listeners? Well, you know, again, this might sound like a little bit of a pitch towards getting people to go into neurology and pursue neuromuscular medicine. But what I would say, and I think it applies to patients in the community too, is the pace and rate at which things are developing and evolving and changing is just staggering. And our field is rapidly changing and

Things that I think a number of us in our field never thought we'd see in our career is now happening with

again, as I was alluding to the breakthroughs that have happened in ALS therapeutics and really redefining what's possible, I'd say that that's just one example of many where it's this really beautiful kind of marriage of enhanced knowledge, but also enhanced technology and therapeutics that really makes the next few decades of what we do really encouraging to consider. So I

I wish you very good luck in improving the lives of so many people who need your help, doctor. Absolutely. Dr. Buccelli, you are just doing amazing, meaningful, wonderful work. And I thank you. And I thank you personally. You are one of my heroes and really have helped me in my journey. And thank you. Thank you for being a guest on It Happened to Me Today.

You really have helped share your wonderful insight and wonderful information on neuromuscular neurology. And we've learned so much from you. Thank you. Thank you for being here today. It happened to me. I'm not alone and neither are you. Very much appreciate it. And I'm flattered by the words. I don't know if I deserve them, but I'm very, very much appreciative. And thanks for the opportunity to chat.

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