Identifying Biomarkers in ALS Patients Using Neuronal Derived Extracellular Vesicles

Sponsor
Fondation Ophtalmologique Adolphe de Rothschild
Study ID
NCT07334743
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Accepted

Study Details

Rationale. ENGRAILED1 (EN1) is under consideration as a therapeutic approach for amyotrophic lateral sclerosis (ALS). To assess EN1 target engagement in patients, we aim to identify EN1-responsive biomarkers suitable as Prentice-style surrogate endpoints. We will discover candidates by RNA-seq of neuron-derived extracellular vesicles (NVEC) immuno-isolated from blood. Establishing such biomarkers would enable and de-risk early-phase (I/II) EN1 trials. Primary endpoint. Discovery: RNA-seq identification of circulating NVEC-borne biomarkers that differ between sporadic ALS patients and healthy controls. EN1 modulation: Demonstration that these biomarkers are modulated by EN1 in En1+/- mouse models and in ALS patient iPSC-derived motor neurons. Design. Prospective cohort, N=60 (30 sporadic ALS; 30 healthy controls matched on age/sex). Population. Adults undergoing diagnostic work-up for suspected sporadic ALS; healthy volunteers without neurological disease. Key procedures and timeline. Baseline (M0, inpatient): ALSFRS-R, MRC, hand dynamometry, eye-movement recording (MOC); NCS/EMG (NUMIX), TMS/MEP with cortical excitability; neuropsychology; brain \& spinal MRI; pulmonary function testing; CSF (10 mL) and blood (15 mL) for clinical labs and research (NVEC immunocapture → RNA-seq; proteomics). Follow-up: M6 clinic visit (repeat clinical/electrophysiology/neuropsychology/PFTs as per care) with blood (15 mL); additional routine follow-ups at M12, M18, M24 (clinical; MOC at M12 and M24). Controls: single visit with blood (3×5 mL EDTA) and cortical excitability; brain MRI for targeting. Sample size. 60 participants total (30 ALS, 30 controls).

Key Dates

First listed
Jan 12, 2026
Start date
Sep 17, 2025
Status verified
Dec 2025
Primary completion
Sep 30, 2029
Completion
Sep 30, 2029

Study Design

Enrollment
60 participants (estimated)

Arms

  • Arm: patients with ALS
  • Arm: controls without ALS

Primary Outcome Measure

Identification by RNA-seq of biomarkers carried by neuron-derived extracellular vesicles (NVEC) present in the blood of ALS patients [ Time Frame: at inclusion visit, month 6 ]

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