NeuroVoices: Kuldip Dave, PhD, on Exploring Neural Regeneration in ALS and Beyond

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The senior vice president of research at The ALS Association discussed insights into neural regeneration therapies and their potential to restore function in neurodegenerative diseases.

Kuldip Dave, PhD

(Credit: LinkedIn)

Neural regeneration has emerged as a pivotal area of research in neuromuscular diseases, aiming to restore function by repairing or replacing damaged neural tissues. Recent studies have highlighted the challenges and potential strategies in this field. For instance, a narrative review in Frontiers in Neurology summarized the current understanding of the limited regenerative capacity in the human central nervous system (CNS) and discussed the intra- and extracellular elements necessary for effective neural regeneration.¹Advancements in neuromuscular disease research have also emphasized progress in understanding disease mechanisms and exploring therapeutic interventions.² These insights may underscore the critical importance of neural regeneration in developing effective treatments for neuromuscular disorders.

This growing interest in neural repair was well represented in a session presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 16-19 in Dallas, Texas, that was chaired by Kuldip Dave, PhD.³ In the session, one speaker examined whether amyotrophic lateral sclerosis (ALS) could transition from a progressively debilitating disease to a recoverable one by exploring neural repair in both the CNS and peripheral nervous system. Another speaker expanded this perspective through the lens of spinal cord injury. Adding another dimension, an additional speaker emphasized the critical role of glial cells in neural plasticity. Closing the session, a speaker presented a novel noninvasive multi-site direct current stimulation approach aimed at slowing ALS progression. Collectively, these presentations underscored the growing potential of neural regeneration to transform outcomes for patients with neuromuscular disorders.

In a new iteration of NeuroVoices, Dave, senior vice president of research at The ALS Association, reinforced this optimism by sharing a powerful personal anecdote that highlighted the real-world impact of neural regeneration therapies. He recounted the experience of sitting beside a patient with ALS, who demonstrated functional improvement after treatment with tofersen (Qalsody; Biogen). Dave also recapped key points from the 2025 MDA conference session he chaired, where experts discussed both pharmacological and nonpharmacological approaches to neural repair across conditions such as ALS and spinal cord injury. He emphasized the need to explore glial cell involvement and dual-targeted therapies that address both neurodegeneration and regeneration, reinforcing the hope that these approaches could one day make debilitating neuromuscular diseases more manageable.

NeurologyLive: Why was it important to highlight “neural regeneration” as a topic at the MDA conference?

Kuldip Dave, PhD: First of all, I want to thank MDA for inviting me to chair this really important session on neural regeneration. And before I talk about neural regeneration, let me ground this in a patient experience I had last year.

I went to a fundraising gala in San Diego and was sitting next to a person living with ALS. We were both at the same table because we were both supposed to go on stage and present for a few minutes. His name is Mark Berman, and he was really excited to show me something on his phone. He opened his phone and showed me a video of himself struggling to move his arms. He was in a wheelchair and had very limited mobility. After showing me that video, he said, “Look what I can do now.” He then reached out in front of him, picked up a glass of water, and held it up. I was just floored by what I saw.

He told me, “This is thanks to the drug I’m on—tofersen.” He is a person living with ALS who has an SOD1 gene mutation, and because of that, he is on this therapy, which was FDA-approved a couple of years ago. It’s a genetic therapy that corrects the mutation in the SOD1 gene. Sitting next to him, I was amazed. As neuroscientists and neurologists, we are all trained to think about neurodegenerative diseases in terms of therapies that, at most, could slow down or stop disease progression—but recovery of function is something new.

And it’s not just me sitting there with Mark. There’s now a publication from Tim Miller, MD, PhD’s lab at Washington University that followed 7 patients on tofersen, showing that 6 out of 7 either had their disease completely stopped—so their function remained stable—or, in 5 out of the 7 cases, had an actual improvement in function. This is why neural regeneration is such a critical topic. We now have real-world data. I saw it firsthand sitting next to Mark Berman. Then there’s the publication from Miller’s lab, along with several real-world data papers from Italy and Germany confirming that tofersen is restoring function.

This raises an important question: If function is being restored, why is that the case? Is it because more neurons are being generated? Are neurons regenerating? Are they making better connections through sprouting? These are questions we don’t yet have answers for, but that’s exactly why it was critical to discuss this topic at MDA.

What were some of the high points of the 4 talks in the session you chaired?

As I mentioned, MDA asked me to chair a session on neural regeneration, and we wanted to explore what is hopeful in this field—what kinds of targets and biological pathways researchers are pursuing. So, we brought together 4 speakers who could provide different perspectives on neural regeneration.

The first was Brett Morrison, MD, PhD, from Johns Hopkins University, who spoke from the ALS perspective. He discussed how neural repair can occur in both the central and peripheral nervous systems and highlighted new potential targets, such as MCT1, for neural repair. He also touched on tofersen and the amazing results we’re seeing with that therapy, but focused on what might be happening at the biological level. That was a highlight from the ALS perspective.

But ALS isn’t the only disease where neurons degenerate. In ALS, neurodegeneration happens over months and years, whereas in spinal cord injury, neural degeneration can occur very acutely in a short period. Our second speaker, Binhai Zheng, PhD, from UCSD, approached neural regeneration from a spinal cord injury perspective. He discussed targets like BACE1 and MUSK inhibition—important mechanisms in acute neurodegeneration following spinal cord injury.

Our third speaker, Isobel Scarisbrick, PhD, from Mayo Clinic, provided a very different perspective. While Morrison and Zheng focused on neural repair and neuronal targets, Scarisbrick highlighted the critical role of glial cells in neural regeneration. She emphasized that we can’t think about neural regeneration in isolation; the supporting cells of the nervous system—the glia—play an essential role. Neurons and glia work together for any kind of repair or regeneration to occur. That was a really unique perspective neuroscientists need to keep in mind when developing therapies.

The fourth and final talk took a completely different approach to neural repair. Nader Yaghoubi, MD, PhD, from PathMaker Neurosystems, discussed noninvasive brain stimulation as a way to promote brain repair. This is very unique. While the first three talks focused on pharmacological approaches, Yaghoubi’s talk explored mechanical methods—how stimulation might enhance protein repair, increase neuronal repair, and reduce neurodegeneration.

This session was incredibly exciting because we saw perspectives from ALS and spinal cord injury researchers converging on similar pathways, despite one being a chronic condition and the other an acute injury. We also discussed glial cells, which play a role in both chronic and acute injury, and a mechanical, nonpharmacological approach to neural repair. It was a great session that reinforced the idea that there are multiple ways to approach neural repair, and this can have a major impact on future therapies.

What should we consider as we move forward with therapies targeting neural regeneration?

Going back to the MDA conference, I attended a lunchtime session on gene therapy in spinal muscular atrophy (SMA). The discussion focused on onasemnogene abeparvovec (Zolgensma; Novartis) and its impact on SMA. The data presented was remarkable—it showed how this gene therapy, which targets specific gene mutations in SMA, is having a real impact. It’s helping not only individuals diagnosed with SMA but also those who started therapy preemptively because they had the gene but hadn’t yet developed symptoms. The results were astounding—children who would have otherwise been severely affected are now able to meet developmental milestones.

SMA, in many ways, has become a livable disease with Zolgensma. And this isn’t about promoting one particular gene therapy—it’s about the hope that if we target the right pathways with the right therapies, we could make ALS or even spinal cord injury more manageable.

One key consideration as we develop these treatments is the role of glial cells. Could we develop a neural therapy that also incorporates glial support? Could glial cells enhance neural regeneration? Another consideration is whether stopping neural degeneration and promoting neural regeneration require distinct approaches. These might be separate therapeutic targets, meaning that in the future, we may need to combine treatments—one to slow down the disease and another to actively repair neurons. Of course, we don’t have those capabilities today, but these are important guiding principles as we work toward neurorepair and neuroregenerative therapies.

Is there anything else you’d like to add or any closing remarks on your experience at the 2025 MDA conference?

I just want to commend MDA for organizing a conference that serves as an umbrella for all neuromuscular diseases, including ALS. At the same time, the ALS Association is also playing a crucial role by hosting the ALS Nexus Conference in August 2025 in Dallas, Texas.

While MDA takes a broad approach to neuromuscular diseases, the ALS Association is diving deeper into ALS-specific research and highlighting key questions in the field. I want to extend an invitation to researchers, people living with ALS, scientists, and healthcare professionals who are interested in learning more about ALS and the potential for future neural regeneration therapies.

Transcript edited for clarity. Click here for more MDA 2025 coverage.