Single-cell profiling of peripheral nerves to find blood and skin biomarkers and new targets for ALS
Translating Single-cell Vulnerability Into Novel ALS Biomarkers and Therapeutic Targets: Towards a Liquid Nerve Biopsy
This project will try to find proteins in peripheral nerves, blood, and skin that signal early ALS in adults with recent-onset disease, people with genetic risk, and healthy controls.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 400 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta Academic / other |
| Locations | 4 sites (Monserrato, California and 3 other locations) |
| Trial ID | NCT07268833 on ClinicalTrials.gov |
What this trial studies
The project uses single-cell systems biology and histopathology on nerve tissue obtained during diagnostic nerve biopsies from living ALS patients and complementary preclinical mouse models. Investigators will map cell-type–specific molecular changes in peripheral nerves (motor axons, Schwann cells, endothelial cells, fibroblasts, macrophages) to identify early dysfunctional states. Candidate protein biomarkers will be selected from tissue signatures and screened and validated in patient biofluids and minimally invasive skin biopsies to create a 'liquid nerve biopsy' profile. The work aims to generate specific early-stage peripheral biomarkers and nominate molecular targets for future therapeutic development.
Who should consider this trial
Good fit: Ideal candidates are adults (≥18) with ALS diagnosed by the revised El Escorial criteria within 24 months of symptom onset, adults with a known genetic susceptibility to ALS before symptoms, and healthy adult controls.
Not a fit: Patients with advanced respiratory or nutritional failure (including FVC <60%), significant hepatic or chronic renal failure, active infections or metabolic conditions that affect biomarker levels, or unrelated neuromuscular disease are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, this could provide blood- or skin-based biomarkers that detect ALS earlier and improve how patients are selected and monitored in treatment trials.
How similar studies have performed: CSF- and CNS-derived biomarker efforts have shown promise, but a single-cell, peripheral nerve–focused liquid biopsy approach is relatively novel and currently supported mainly by preliminary tissue data.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria for als patients: * Age equal or over 18 years old * ALS patients, diagnosed accordingly to the revised El Escorial Criteria * Disease duration \<24 months from symptom onset. Exclusion Criteria for als patients: * FVC \<60%; * nutritional or respiratory failure; * significant hepatic or chronic renal failure or any interveninginfective or metabolic conditions potentially influencing CBs levels. Inclusion criteria for ALS pre-symptomatic patients * Age equal or over 18 years old * Patients with genetic defined susceptibility to ALS and one or more strict relative affected from ALS Exclusion criteria for ALS pre-symptomatic patients * significant hepatic or chronic renal failure or any interveninginfective or metabolic conditions potentially influencing CBs levels. Inclusion criteria for controls * Age equal or over 18 years old * Subjects without a diagnosis of neurodegenerative disease or neuromuscular disorder. Exclusion criteria for controls • significant hepatic or chronic renal failure or any interveninginfective or metabolic conditions potentially influencing CBs levels. Inclusion criteria for non ALS neurodegenerative patients * Age equal or over 18 years old * For AD: Diagnosis according to 2018 NIA-AA Framework for Alzheimer's Disease * For FTD: Diagnosis according to 2011 International Behavioural Variant FTD Criteria Consortium * For PD: Diagnosis according to 2015 Movement Disorder Society criteria * For DLB: Diagnosis according to 2017 Fourth Consensus Report of the DLB Consortium Exclusion criteria for non ALS neurodegenerative patients * significant hepatic or chronic renal failure or any interveninginfective or metabolic conditions potentially influencing CBs levels. Inclusion criteria for neuromuscular disease patients * Age equal or over 18 years old * Presence of axonal or demyelinating neuropathy Exclusion criteria for neuromuscular patients * significant hepatic or chronic renal failure or any interveninginfective or metabolic conditions potentially influencing CBs levels.
Where this trial is running
Monserrato, California and 3 other locations
- Azienda Ospedaliero Universitaria di Cagliari — Monserrato, California, Italy (Recruiting)
- Fondazione IRCCS Istituto Neurologico Carlo Besta — Milan, Italy (Recruiting)
- IRCCS Ospedale San Raffaele SRL — Milan, Italy (Recruiting)
- Azienda Ospedaliera Universitaria Federico II — Naples, Italy (Recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.