Updates in Gene Therapy, Biomarkers, and AI Advancements for ALS Care Management

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EP: 1.Updates in Gene Therapy, Biomarkers, and AI Advancements for ALS Care Management

Recent advancements in amyotrophic lateral sclerosis (ALS) research may reshape how clinicians understand and help patients manage the disease, with potential therapies slowly emerging that aim to target both genetic and cellular pathways. Alongside these strides, there seems to be a growing emphasis on a holistic care approach following diagnosis to offer additional support for patients throughout the disease course. Furthermore, genetic testing could become more valuable in guiding diagnosis and offering refined treatment decisions for patients. Together, these developments in the field might highlight a shift toward more comprehensive, individualized care strategies that can address both the biological and lived experience of patients with ALS.

In collaboration with The ALS Association, NeurologyLive^® recently held a roundtable discussion with a panel of ALS experts who talked about updates in ALS research that show potential to improve clinical care, including the expanding role of genetic testing and personalized treatment. The guest neurologists featured in this conversation included Bjorn Oskarsson, MD, associate professor of neurology at Mayo Clinic in Florida and director of the ALS Center of Excellence; John Novak, MD, neuromuscular specialist and director of the ALS Clinic at Ohio Health; Christina Fournier, MD, associate professor of neurology at Emory University and co-director of the Emory ALS Center.

In this first episode, clinicians highlighted a few of the potential groundbreaking advancements in ALS research and clinical care. They discussed the recent approval of tofersen (Qalsody; Biogen), the first FDA-approved gene therapy targeting SOD1 mutations, as a milestone that may pave the way for additional gene-based treatments. The panel also emphasized the growing role of biomarkers like neurofilament light and advanced imaging in improving diagnosis and prognosis for ALS. Furthermore, they explored the moving integration of artificial intelligence (AI) in both research and care, ranging from drug discovery to the development of personalized, AI-generated voice clones that restore communication for patients with speech loss.

Transcript edited for clarity.

Isabella Ciccone, MPH: What recent developments in ALS research do you think hold the most promise in clinical care?

Christina Fournier, MD: I think there's a lot of excitement with the approval of tofersen, which is the first gene therapy for ALS. This is only for people who have a pathogenic variant in the SOD1 gene, which is a very small percentage of the total ALS population, but I think it tells us that we can do this. It's an exciting first step. It's a treatment we think meaningfully impacts the course of things. Now I think we're on the way to mechanism-specific treatments that are only going to keep getting developed from here. I think it's an exciting first step, and we're seeing progress on the scientific front that I think will get translated into more approved therapies in the future. So, I think this is a big and important first step, and we're excited to see what comes next.

Bjorn Oskarsson, MD: I would normally echo that. Again, where we understand or see a cause of ALS, we have now shown that we can address it. So, there are people now living with ALS, some even getting stronger with ALS. It's a very hopeful time.

John Novak, MD: Yeah, I think those are probably the biggest things we've got, right? That's the newest thing. We are targeting therapies directly for genetic causes that will spill over into sporadic. We will learn how to deal on a molecular level much better with this disease and target it. I think the other big thing that I hope to see change is in biomarkers. I think biomarkers are a way to hopefully someday classify people physiologically—what's going on—and target those therapies toward that. But then also, it's accelerating our discovery of new drugs. We can look to see does this work in a person and not have to wait 2, 3 years to see how long they live, or 6 months. For some of these trials, maybe we can screen therapies faster and get them out to people quicker as we learn more.

Bjorn Oskarsson, MD: I think biomarkers for diagnosis have come a long way in recent times. We've had basically the complicated neurological exam as the tool that served us well for over 100 years. Electrophysiology of the lower motor neurons has been strong for a long time—we've been able to use that for quite some time. But now we also have imaging that is starting to get fairly reliable at picking up ALS—definitely the upper motor aspects of ALS. We have neurofilament light, which has made its entry into clinical practice. That helps us make a diagnosis quicker and make estimates on prognosis. Again, it isn’t the perfect measure, but it’s better than the lack of any measures that we had before.

Christina Fournier, MD: Along those lines, I think we're really early on using AI to help us with ALS, but I think we're starting to crack the surface on in this disease maybe, it's so complex in terms of mechanisms and clinical phenotypes and things like that—that we might be able to harness AI to kind of make sense of things that make sense to us clinically. I think we're only just beginning to use AI for the purposes of drug discovery and ALS subtypes and things like that. But I think it's a exciting field that we're going to see a lot more of as we learn to use AI in our favor.

Bjorn Oskarsson, MD: I guess we have our first AI applications for our patients with AI-created voices for patients who’ve lost their voice. We can now get a voice generated using very small amounts of old voice clippings. I mean, that’s the first AI use that I see helping my patients.

Christina Fournier, MD: It's very cool, this voice cloning. So, they take old voice recordings and create a voice that sounds like the patient did before they had any voice changes—using old recordings of their voice. And it's really good. I mean, the emotion in their voice, the way that they kind of pause and express things, and even the ums and the likes and things that were specific to the way they talked get captured in this voice clone. The one I just heard in clinic last week was incredible. It really was game-changing for the person I heard using it, because they lived in this multigenerational house with a big family and were still able to jump in and be a part of all that family interaction. So yeah, it's a cool example of AI for good in ALS. And like I said, I think it's only the beginning.

John Novak, MD: We just had a woman give a speech using that voice at a baseball game. And it was her giving the speech through her device. It’s amazing, through the microphone and everything. It was just like she was never affected. It was really, really moving. I think for their family too, it's a cool thing.