Targeting the Root: Advancing ALS Therapies and Biomarkers Through Precision Science
July 22, 2025
QurAlis and partners are pioneering a new wave of ALS research, combining targeted therapies like QRL-101 with innovative biomarker discovery to address the disease at its core.
Advancing Targeted Therapies for ALS Through Ion Channel Modulation
QurAlis is working on an exciting development; a targeted therapy for ALS called QRL-101. This treatment focuses on a common but often overlooked feature of ALS: neuronal hyperexcitability, or the overactivation of nerve cells. This abnormal nerve activity, seen in up to 70% of ALS patients, is believed to contribute to how the disease progresses.
- ALS 101:
- DNA (Deoxyribonucleic Acid) is the instruction manual for building and running every cell in the body. It carries the genetic code that determines how our bodies develop and function.
- RNA (Ribonucleic Acid) is the messenger that helps turn those DNA instructions into action—mainly by helping make the proteins that keep our cells alive and working properly.
- Hyperexcitability is when nerve cells (neurons) become too easily activated or “triggered,” often firing more often or more intensely than they should. This abnormal activity can disrupt normal brain and nerve function and is linked to conditions like ALS, epilepsy, and chronic pain.
- Mis-splicing refers to errors in how the genetic instructions from a gene are pieced together to make a functional protein. These errors can lead to a faulty or missing potassium channel protein, which may cause nerve cells to become overactive, seen in many people with ALS.
- Extracellular vesicles (EVs) are tiny bubble-like particles released by cells into bodily fluids like blood and spinal fluid. They carry bits of the cell’s internal material, such as proteins, RNA, and lipids, and act like messengers, helping cells communicate with one another. In diseases like ALS, EVs can contain specific disease-related signals, making them a valuable tool for tracking what’s happening inside the nervous system through simple, non-invasive tests.
QRL-101 is part of QurAlis’s broader approach to treating diseases of the nervous system through two main strategies: fixing faulty ion channels (like potassium channels) and restoring healthy RNA activity. QRL-101 works by precisely targeting the potassium channel Kv7.2, that helps “calm” overactive nerve cells, without the side effects that limited earlier drugs like ezogabine.
In a recent Phase 1 trial in healthy volunteers, QRL-101 showed that it could reduce hyperexcitability in the brain, proving that it hits its biological target. It also changed disease-relevant markers tied to ALS progression, and it did all this with minimal side effects (most were mild and no serious issues were reported). QurAlis is now preparing to test a longer-lasting version of the drug in people living with ALS.
Importantly, these early results were confirmed using advanced brain and nerve monitoring tools. The drug even showed strong effects at low doses, suggesting it may offer a safer, more effective way to treat ALS by targeting a key disease mechanism early and directly.
“QRL-101 is well-positioned to be a potential best-in-class therapeutic with high selectivity, lack of off-target engagement, and multiple formulations for daily or twice-daily dosing to enable application in neurodegenerative and neurological diseases, including ALS and epilepsy.” – Emma Bowden, Senior Vice President, Head of Clinical Development, QurAlis)
💡Key Takeaway:
QRL-101 is a promising, well-tolerated treatment candidate that could address hyperexcitability in a broad population of ALS patients. Early biomarker data confirms that the drug is doing what it’s supposed to, laying the groundwork for potential disease-modifying effects.
KCNQ2 Mis-Splicing: A Precision Biomarker for ALS
Another promising project led by QurAlis, with partners at Northwestern, USC, and Emory, is the development of a blood test to detect mis-splicing the KCNQ2 gene, which encodes the Kv7.2 protein and is linked to hyperexcitability in ALS.
By analyzing tiny particles in the blood called extracellular vesicles (EVs), they hope to identify individuals with this gene disruption and explore how it could help with diagnosis, tailoring treatments, and tracking how well therapies work.
💡 Key Takeaway:
By tracking KCNQ2 mis-splicing in EVs, this project is building a non-invasive tool to connect TDP-43 pathology to functional deficits, offering a promising biomarker and therapeutic target in ALS.
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