NeuroSense reports additional Phase 2 PARADIGM data for PrimeC: understanding the latest findings

PrimeC, an investigational therapy by NeuroSense Therapeutics, combines two existing prescription drugs: the antibiotic ciprofloxacin and the anti‑inflammatory drug celecoxib. Together, they are thought to target three biological processes linked to ALS: inflammation in the brain, abnormal microRNA activity (small RNA molecules that help regulate how genes function), and iron dysregulation in neurons. Through these processes, PrimeC is speculated by NeuroSense to decrease neuronal damage and slow disease progression. 

On June 29, 2026, NeuroSense Therapeutics announced new findings from its Phase 2 PrimeC trial, including results related to TDP-43, a protein that is abnormally aggregated in more than 97% of ALS cases and is considered one of the defining hallmarks of the disease. TDP-43 is found primarily within the nucleus of a cell, where it helps to regulate essential cell processes, but in ALS, it becomes trapped outside in the cytoplasm forming clumps or aggregates. These clumps, and the loss of TDP-43 cellular function, are theorized to contribute to motor neuron damage and death.

NeuroSense reported that PrimeC significantly reduced TDP-43 levels compared with placebo, making it the first trial to declare a reduction in this protein. However, it is important to understand that researchers still do not know whether changes in this TDP-43 measurement are linked to meaningful improvements in disease progression, function, or survival, and to look at it in context.

PrimeC was investigated in a Phase 2 trial (PARADIGM), enrolling 68 participants living with ALS. Participants were randomized 2:1 to receive either PrimeC or placebo for six months, followed by a six-month open-label extension, meaning all participants received PrimeC.

While the study reported some differences between the PrimeC and placebo groups, there is still not enough evidence to conclude that PrimeC is effective for ALS. However, the findings suggest PrimeC is affecting the biological pathways it was designed to target, which is an encouraging sign and supports further investigation. The next step is determining whether these biological changes translate into meaningful benefits for people living with ALS, as researchers continue to work toward a better understanding of the disease and what drives it.

We discuss the Phase 2 PARADIGM results in more detail in our latest Clinical Research & Trials Update.

In the study, TDP-43 was measured using a specialized blood test that looked at tiny packages released by nerve cells (neuron-derived extracellular vesicles, or NDEs). A recent commentary by Dr. Jenna Gregory, UK, emphasizes that, while this finding is scientifically interesting, researchers do not yet know how to interpret changes in extracellular vesicle TDP-43 in ALS. A decrease could potentially reflect a beneficial biological effect, but it could also reflect other processes, such as simply changes in how TDP-43 is released, retained inside cells, cleared, or transported.

Interpreting these findings is further complicated by the fact that we still do not fully understand the role of the TDP-43 protein in ALS. Although it is closely linked to the disease, it remains unclear whether it is a primary driver of disease progression, a consequence of the disease process, or both.

In other words, the change in TDP-43 suggests that PrimeC is affecting ALS-related biology, which can be noteworthy. However, seeing TDP-43 levels increase or decrease does not, on its own, tell us whether disease progression is improving or remaining unchanged.

This highlights one of the challenges in ALS research and trials – biomarkers can provide important clues, but they must be validated and interpreted alongside clinical outcomes.

NeuroSense first announced plans to advance PrimeC into the larger Phase 3 PARAGON trial in late 2024, with the study expected to begin sometime in 2026. This larger study will help determine the therapy’s efficacy.

On July 22, 2026, NeuroSense Therapeutics also announced that it intends to move forward with a New Drug Submission (NDS) to Health Canada following a pre-submission meeting with the agency. The decision to pursue a Health Canada submission may affect plans for Canadian sites to participate in the upcoming Phase 3 study.

As with all ALS clinical trials, ALS Canada remains hopeful that a larger, well-designed confirmatory trial can demonstrate a meaningful benefit for people living with ALS. We know that many people living with ALS cannot afford to wait years for more answers, and we feel the same urgency. Larger trials remain essential to determine whether early signals seen in smaller studies translate into real clinical benefit, as many ALS therapies have shown encouraging results in Phase 2 studies, but were ultimately unable to demonstrate efficacy in larger confirmatory trials.

For this reason, the next phase of research for PrimeC is important. We will continue to monitor developments and share updates as they become available.

INSIDE THE SCIENCE

Interested in learning more about why Phase 3 clinical trials are important? Explore our Inside the Science article on the journey of clinical trials and off-label treatments.