Jaime Lewis (Host): Each year in the United States, about 5,000 people are diagnosed with ALS, otherwise known as Lou Gehrig's disease. Today, we're talking about ALS with Dr. Kelly Gwathmey, Director of VCU Health's ALS clinic. Dr. Gwathmey leads the largest ALS clinic in Virginia and an ALS Association-Certified Center of Excellence.

This is Healthy with VCU Health. I'm Jamie Lewis. Hello, Dr. Gwathmey. Welcome to the podcast.

Dr. Kelly Gwathmey: Hi, Jamie. Thank you so much for having me.

Host: Yes, absolutely. Well, let's start very simply. What is ALS?

Dr. Kelly Gwathmey: So, ALS or amyotrophic lateral sclerosis, which you already said is synonymous with Lou Gehrig's disease, is a rare neuromuscular condition that results from degeneration or damage to the motor nervous system. So, our patients unfortunately present with painless, progressive muscle weakness, often starting in an arm or a leg. And then, occasionally, it can start in the speech and swallow muscles. With time, it will spread to other limbs or up to the speech and swallow muscles.

And then, unfortunately, our patients ultimately develop respiratory failure, significant shortness of breath due to weakness of the breathing muscles. And our patients pass away from about two to five years from symptom onset.

Host: How does someone wind up getting this disorder, this disease?

Dr. Kelly Gwathmey: Now, Jamie, that's one of the great mysteries, I'm afraid. So, about 90% of our patients have a sporadic form of the disease in which we really don't know why someone gets it. Our current hypothesis is it's a combination of genetic predisposition and exposure to environmental risk factors that results in the neurodegenerative process.

For about 10% or so of patients, there is a genetic reason. And so, that means there's a mutation in one of their genes that's causing the disease. As you might imagine in those cases, usually there's a family history of ALS, but we do test practically everyone these days for a genetic form of ALS and do find patients who are the only ones known in their family to have that genetic mutation.

Host: Okay. Interesting. Well, how do you go about diagnosing ALS?

Dr. Kelly Gwathmey: Thank you for asking that very important question. That is a tricky thing as well, I'm afraid. It is hard to make a diagnosis of ALS, especially early in the disease course. And the reason is a lot of times, the symptoms and the weakness needs to evolve to a point that it is apparent on both the patient's examination in the doctor's office, and then also for the characteristic or typical, we'd say, electrodiagnostic changes on EMG, electromyography to show up. There is no simple blood test for ALS. And so, really, it's just that combination of their exam supported by the electrodiagnostic data, and then you exclude all the other possibilities, the mimics. So, most of our patients will have a brain MRI and spine MRIs and a bunch of lab work as well to look for other things it could be. So, it's a process of elimination and the diagnosis is a diagnosis of exclusion.

Host: Okay. Well, I know that VCU Health, the ALS clinic there, provides rapid access, which is specific, referring to something specific. What does that mean exactly?

Dr. Kelly Gwathmey: Thank you, Jamie. So, we noticed over the past several years that we have a significant diagnostic delay concern in our region. And when I say that, nationally, patients with ALS will go 12 months from symptom onset before they are officially diagnosed and may see up to four other doctors before ultimately getting a diagnosis. And many are misdiagnosed along the way.

And so, when we realize that in our community that diagnostic delay issue was even greater, we piloted this rapid access clinic that started in September of 2022. And what we did before we opened the doors for this clinic was we raised disease awareness, we reached out to community Primary Care providers, Ear, Nose and Throat doctors, gastroenterologists, spine surgeons; electromyographers, the doctors in the community that do those electrical tests to educate them on the signs and symptoms of ALS and make them aware of this rapid access clinic.

And within this clinic, we will see any patient suspected of having ALS within four weeks of referral with same day electrodiagnostic testing if necessary. And we have a small multidisciplinary team. It's smaller than our very large ALS clinic that we have on Tuesdays, this clinic's on Fridays. And we have a social worker, respiratory therapist, we have our nurse navigator, a dietician, and an occupational therapist.

And so, it is kind of a fast-track way to get a diagnosis. And if you are diagnosed with ALS, then we will quickly start mobilizing resources to support the patient, and we know that the sooner the patient is diagnosed with ALS, the sooner they can access disease-modifying therapies, the better their clinical outcomes. They will live longer and do better in the long run. And so, it has made a difference in our community. When we analyzed the preliminary data about a year ago now, it showed that we improved the diagnostic delay by about two months, which is significant in ALS. And so, we're very proud of this program. It's the first of its kind in the country.

Host: Wow. Okay. Well, you mentioned that, let's say in a normal non-rapid access situation, it can take quite a while. People can wind up going to several different providers to try to nail down what this is they're looking at. But if we were going to tell somebody who is maybe wanting to know what to look for, are there any hallmarks of ALS that a person can see and know what to ask for when they see a provider?

Dr. Kelly Gwathmey: Yes, of course. And so, if a patient has weakness that starts either in their arm or their leg, the so-called limb-onset ALS, then what we would expect is that there is, again, painless, progressive muscle weakness with atrophy, so loss of muscle bulk. There's often muscle twitching or fasciculations associated with it. And then, the weakness will spread and worsen in that limb and then spread to the other limb on the other side, or if it starts in the hand spread down to the leg or vice versa. And then, if it starts in the speech and swallow muscles, people will notice that they're having slurring of their speech. People are having a hard time understanding them. They might have difficulty swallowing foods, especially crumbly foods and leafy vegetables and firmer meats.

And then, with time again, they will develop shortness of breath. And with that, it tends to be with exertion initially if they're climbing a flight of stairs or worse at night when they're lying down flat in bed, which is called orthopnea. And so, those are the symptoms we always keep an eye out for. Since it is a pure motor nervous system problem, we would not anticipate or expect that there would be numbness or loss of sensation or any pins and needles or burning pain, any symptoms along those lines.

Host: Okay. Well, as far as advancements go, what kind of technological advancements are you seeing in this field?

Dr. Kelly Gwathmey: That's a great question as well. So first, I always tell patients in terms of how we treat this disease, we have a lot of research to show that multidisciplinary care itself being followed in a multidisciplinary clinic like the one we have at VCU really makes a difference. We know that patients that are followed in that standard of care model, have improved access to disease-modifying therapies, equipment, they have better quality of life, they stay out of the hospital more and you live longer. So, that in and of itself is a treatment approach.

And then, secondly, in terms of disease-modifying therapies, we currently have three different drugs on the market that slow the progression of the disease. Starting with riluzole that was approved in 1995, and then edaravone in 2017. And most recently, tofersen, which is a very novel therapeutic. It's an antisense oligonucleotide treatment that is specifically targeting a rare form of genetic ALS called SOD1. So, the great news about that drug development is that it's really changed the way we think about ALS. The patients who qualify for that drug will have, in some cases, even improvement in their symptoms, or stabilization of their weakness once they start treatment, which we have never seen before in the ALS field. So, it's a real cause for optimism that we can continue to create and develop and test drugs that work as well, if not better, than that one. So, it's extremely exciting.

And then, you know, on that note, we're all extremely eager to understand the disease better, to identify and test better therapeutics in ALS so we can make this a livable disease. And so, there's been a huge push in the last few years to conduct large-scale observational studies that look at biomarkers and disease progression based off of the different types of ALS patients have. And when I say biomarkers, this could be signals in the patient's body, in their blood or their spinal fluid that tells us kind of how the disease is going to behave with time and how it can help us prognosticate or understand the disease trajectory for that individual. So, there's a lot of really good work taking place right now, and especially at VCU trying to understand these things.

Host: Well, wonderful. I'm happy to hear that. And thank you so much, Doctor, for this very important discussion. I appreciate your time.

Dr. Kelly Gwathmey: Thank you for having me.

Host: For more information about VCU Health's ALS Clinic, call 804-828-0856. to be considered for the Rapid Access Program, patients must be screened using the thinkALS tool, which you can find at als.org. To listen to other podcasts from VCU Health, visit vcuhealth.org/podcast. This is Healthy with VCU Health. I'm Jamie Lewis. Thank you for listening.​