Blood RNA biomarkers for ALS using neuron-derived extracellular vesicles

Identifying Biomarkers in ALS Patients Using Neuronal Derived Extracellular Vesicles

This will try to see if RNA signatures in neuron-derived extracellular vesicles from blood can identify biomarkers in adults with suspected sporadic ALS compared with healthy volunteers.

Quick facts

• Study type: Observational
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fondation Ophtalmologique Adolphe de Rothschild (Research network)
• Locations: 1 site (Paris)
• Trial ID: NCT07334743 on ClinicalTrials.gov

What this trial studies

Researchers will collect blood from 30 adults with suspected sporadic ALS and 30 age- and sex-matched healthy volunteers and immuno-isolate neuron-derived extracellular vesicles for RNA sequencing. They will compare RNA expression patterns to discover NVEC-borne biomarkers that differ between patients and controls. Candidate biomarkers will be tested for EN1 modulation in En1+/- mouse models and in induced pluripotent stem cell–derived motor neurons from ALS patients to seek Prentice-style surrogate endpoints. The prospective cohort design aims to identify circulating markers that could enable and de-risk early-phase EN1 therapy trials.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) undergoing diagnostic work-up for suspected sporadic ALS who can give informed consent and attend inpatient evaluations at the study center, with matched healthy adults without neurological disease serving as controls.

Not a fit: People with familial/genetic ALS, active infection within 4 weeks, ongoing cancer treatment, pregnant or breastfeeding individuals, or those unable to provide informed consent are excluded and are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, identified biomarkers could enable earlier, less invasive monitoring and speed up development of EN1-based therapies for ALS.

How similar studies have performed: Prior studies using neuron-derived extracellular vesicles and RNA profiling have reported promising biomarker signals in neurodegenerative disorders, but applying EN1-responsive NVEC biomarkers specifically to ALS remains relatively novel.

Eligibility criteria

Inclusion Criteria:

For patients :

Age ≥ 18 years. Diagnostic suspicion of amyotrophic lateral sclerosis (ALS). Planned inpatient admission in the HFAR neurology department for the standard diagnostic work-up as part of routine care: clinical evaluation, neuropsychological assessment, nerve conduction studies/EMG, motor evoked potentials (TMS/MEP), brain and spinal MRI, pulmonary function testing, lumbar puncture, and standard blood tests.

Explicit written informed consent to participate in the study. Affiliation with or beneficiary of a social security system.

Non-inclusion criteria:

Patient under legal protection/guardianship. Pregnant or breastfeeding woman. Active infection within the 4 weeks preceding biological sampling. Ongoing diagnosis and management of cancer.

Secondary exclusion criterion:

ALS diagnosis not confirmed.

For Healthy Controls :

Age ≥ 18 years. Explicit written informed consent to participate in the study. Affiliation with or beneficiary of a social security system.

Exclusion Criteria:

* Patient under legal protection/guardianship.
* Pregnant or breastfeeding woman.
* Diagnosed neurological disease.
* Self-reported cognitive impairment.
* Active infection within the 4 weeks prior to biological sampling.
* Current diagnosis and management of cancer.

Where this trial is running

Paris

• Hopital Fondation Adolphe de Rothschild — Paris, France (Recruiting)

Conditions Amyotrophic Lateral Sclerosis; ENGRAILED1