NATIONAL NEWS (NATICK, Mass.) — — NeuroDex, a precision diagnostics company specializing in the isolation and analysis of neuron-derived extracellular vesicles (NDEs) from blood, today announced new findings supporting NDE-associated TDP-43 as a treatment-responsive biomarker in amyotrophic lateral sclerosis (ALS).
TDP-43 mislocalization and aggregation occur in more than 97% of ALS cases, about 40% of frontotemporal dementia and a substantial proportion of Alzheimer’s-spectrum disease, either as co-pathology or primary pathology (Limbic-predominant Age-related TDP-43 Encephalopathy,LATE). Despite its central role across neurodegenerative diseases, reliable biofluid biomarkers capable of measuring TDP-43 pathology in living patients have been elusive.
Conventional plasma TDP-43 measurements are limited by substantial biological background, as TDP-43 is expressed throughout the body and detected from numerous peripheral cell types. NeuroDex’s proprietary ExoSORT™ platform addresses this challenge by selectively enriching neuron-derived extracellular vesicles from blood, providing a minimally invasive window into molecular processes occurring within neurons of the brain and spinal cord.
Across multiple independent cohorts, ExoSORT-based analysis demonstrated that NDE-associated TDP-43 distinguished sporadic ALS from healthy controls. These findings were reproduced across three cohorts: 75 sporadic ALS versus healthy controls (44% increase, P=0.0003); 25 sporadic ALS versus 30 healthy controls (52% increase, P=0.002); and a third cohort of 52 ALS versus 37 healthy controls, in which NDE-associated TDP-43 was markedly elevated in disease (more than twofold higher; P<0.0001).
Longitudinal analyses further showed that NDE-associated TDP-43 increases over time as disease progresses. In the most recent cohort, NDE-associated TDP-43 rose over time in sporadic ALS and tracked clinical status. Within-patient longitudinal modeling estimated an increase of approximately 45% per year in sporadic ALS, and TDP-43 levels were associated with disease severity as measured by the ALSFRS-R.
“TDP-43 is emerging as a central pathology in neurodegeneration, yet measuring it in biofluids has been a long-standing challenge. A blood-based readout of TDP-43 could enable better patient selection and treatment monitoring and make clinical trials more efficient. These data are encouraging and support moving into clinical validation,” said Dr. Ajay Verma, CEO of Twilight, which works with NeuroDex to develop TDP43 biomarkers for ALS and FTD.
TDP43 can also serve as a treatment response biomarker. In a recent phase 2b randomized, placebo- controlled clinical trial (PARADIGM) conducted by NeuroSense Therapeutics (Nasdaq: NRSN) with its lead product candidate PrimeC (Cudkowicz et al. 2026), NeuroDex applied its ExoSORT workflow to serial samples collected longitudinally from study participants across all scheduled study visits. NDE-associated TDP-43 was measured in serial blood samples obtained throughout the trial, enabling assessment of biomarker trajectories over time in both placebo-treated and actively treated participants.
In this trial, NDE-associated TDP-43 increased over time in the placebo group, consistent with the natural-history pattern observed in NeuroDex’s prior studies. In contrast, participants receiving PrimeC demonstrated a statistically significant reduction in NDE-associated TDP-43 from baseline over the 6-month treatment period.
Notably, the biomarker analyses were derived from the same randomized clinical dataset that demonstrated favorable effects on functional decline, survival, and additional disease-relevant biomarkers. Taken together with NeuroDex’s prior work, these findings strengthen the evidence linking NDE-associated TDP-43 to ALS disease biology and support its continued evaluation in clinical studies as a pharmacodynamic biomarker.
The analysis was performed using NeuroDex’s ExoSORT platform, the first automated and scalable technology designed specifically for enrichment of neuron-derived extracellular vesicles from blood samples “In our Phase 2b PARADIGM clinical trial, PrimeC demonstrated a meaningful slowing of disease progression and an improvement in survival. The opportunity to pair that clinical effect with a blood-based measure of TDP-43 pathology is an important step toward understanding treatment effects on the underlying biology,” said Alon Ben-Noon, Chief Executive Officer of NeuroSense Therapeutics.
Dr. Erez Eitan, NeuroDex CEO added “We are excited to see NDE-associated TDP-43 distinguish disease from healthy controls and change over time in ALSThese results demonstrate the power of our NDE technology to take pathological proteins with broad tissue expression and transform them into neuron-specific biomarkers.”
ABOUT EXOSORT™ AND NEURON-DERIVED EVS
ExoSORT™ is NeuroDex’s proprietary automated platform for the enrichment of neuron-derived extracellular vesicles (NDEs) from blood samples. Using a combination of highly specific neuronal antibodies and a scalable 96-well workflow, ExoSORT™ selectively isolates extracellular vesicles originating from the brain, increasing the neuronal signal by more than 50-fold compared with conventional plasma analyses. By enriching for brain-derived vesicles, ExoSORT™ enables detection of disease-associated proteins that are also present in other tissues, such as TDP-43.
ABOUT NEURODEX
NeuroDex is a precision diagnostics company focused on unlocking the central nervous system through the analysis of neuron-derived extracellular vesicles isolated from blood. Its proprietary ExoSORT™ platform enables researchers and drug developers to measure brain-specific proteins and biomarkers from a routine blood draw, supporting earlier detection, target-engagement readouts, and treatment-response monitoring across neurodegenerative diseases including ALS, Alzheimer’s disease, and Parkinson’s disease.
ABOUT ALS
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that causes progressive paralysis and is typically fatal within 2-5 years of diagnosis. More than 5,000 people are diagnosed with ALS each year in the U.S. alone, with an estimated annual disease burden of $1 billion. The number of people living with ALS is expected to grow by approximately 24% by 2040 across the U.S. and EU.
ABOUT NEUROSENSE PRIMEC
PrimeC, NeuroSense Therapeutics’ lead drug candidate, is a novel extended-release oral formulation combining two FDA-approved drugs, ciprofloxacin and celecoxib, in a unique fixed-dose combination. PrimeC is designed to synergistically target several mechanisms implicated in ALS, including neuroinflammation, iron accumulation, and impaired RNA regulation, with the goal of slowing disease progression.
LEARN MORE: https://neurodex.co
Forward-Looking Statements
This press release contains “forward-looking statements” that are subject to risks and uncertainties. Statements regarding the future application of the ExoSORT™ platform, the development of PrimeC, the timing and outcome of clinical trials including a potential Phase 3 (PARAGON) study, and regulatory engagement are forward-looking and based on current expectations. Biomarker findings described herein are exploratory, were generated in part in collaboration with NeuroSense Therapeutics Ltd., and require confirmation in additional studies. Actual results could differ materially from those anticipated. For additional information regarding NeuroSense, PrimeC, and the PARADIGM study, refer to NeuroSense’s filings with the U.S. Securities and Exchange Commission. NeuroDex undertakes no duty to update forward-looking statements except as required by law.
CITATION: https://pubmed.ncbi.nlm.nih.gov/41837970/
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