Disease Biosignatures in ALS/FTD Spectrum: New Impactful Biological Perspectives Beyond Clinical Approaches

NCT06856850 | Recruiting

• 1 other identifier: PNRR MCNT2-2023-12377336
• Study Type: observational
• Target: 230
• Locations: 1 country
• Sites: 4

Brief Summary

Diagnosis of ALS/FTD disease spectrum is challenging because it largely relies on clinical symptoms. Identifying novel biomarkers is essential for a paradigm shift towards a more precise biological-based diagnosis. To achieve this aim, having access to proper specimens and analytical methods is crucial. Our team of experts in neurology, biology, chemistry, physics, and AI will explore ALS/FTD from novel perspectives using transcriptomics, proteomics, genomics and other innovative approaches to analyzing easily accessible tissues. The seed amplification assay (SAA) will be also exploited to detect pathological TDP-43. This project aims to create disease fingerprints useful for patient stratification and monitoring of disease progression, and to evaluate the therapeutic efficacy in clinical trials, thus overcoming the limits of clinical interpretation. Discovering new biomarkers and cellular pathways will improve the diagnosis and treatment of these devastating diseases.

Conditions

ALS (Amyotrophic Lateral Sclerosis); FTD; Neuropathic; Psychiatric Disorders; Idiopathic Intracranial Hypertension; Frontotemporal Dementia (FTD)

Keywords

Amyotrophic lateral sclerosis; frontotemporal dementia; microbiota; miRNA; protein-NMR; TDP-43; endocytic disfunction; seed amplification assay; peripheral biomarker

Outcome Measures

Primary Outcomes (1)

• Evaluation of SAA accuracy in detecting misfolded TDP-43 in CSF, skin, OM, and tears of ALS and FTD patients.

  the primary outcome of the study will involve investigating the distribution of misfolded TDP-43, a protein associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), using ultrasensitive techniques namely Seed Amplification Assays (SAA). These assays will be employed to detect minute amounts of misfolded TDP-43 in cerebrospinal fluid (CSF), olfactory mucosa (OM), serum, skin, and tears from patients, with a clinical diagnosis of bulbar ALS (bALS; n=32), spinal ALS (sALS; n=105), FTD (n=66), and other non-neurodegenerative neurological conditions (NNC; n=27). By analyzing multiple peripheral tissues from the same patients, the generation of a disease biological fingerprint, obtained by integrating SAA analysis, other biochemical tests together with clinical and instrumental findings will be attempted. We aim to explore the reliability of this approach to improve the clinical diagnosis of ALS and FTD by allowing patient stratification.

  24 months

Secondary Outcomes (5)

• Diagnostic and prognostic peripheral biomarkers identification through Simoa

  18 months

• Diagnostic and prognostic peripheral biomarkers identification through Microfluidic analysis

  18 months

• Diagnostic and prognostic peripheral biomarkers identification through multiplex immunoassays

  18 months

• Metagenomic analysis to evaluate the microbiota composition

  12 months

• Biochemical and structural characterization of selected SAA end products by Western blot and solid-state NMR analysis

  12 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Spinal-ALS (sALS, n=60), Bulbar-ALS (Bals,n=20), FTD (n=36), and NNC (n=10)

You may qualify if:

• Clinical criteria for ALS (Brooks et al., 2000; de Carvalho M., 2008), FTD (GornoTempini et al., 2011; Rascovsky et al., 2011)

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead

Study Sites (4)

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

RECRUITING

Università degli Studi di Napoli "Federico II"

Naples, 80131, Italy

NOT YET RECRUITING

Azienda Ospedaliero Universitaria di Sassari

Sassari, 07100, Italy

NOT YET RECRUITING

Consorzio Interuniversitario Risonanze Magnetiche Metallo Proteine (CIRMMP)

Sesto Fiorentino, 50019, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Mental Disorders; Pseudotumor Cerebri; Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Intracranial Hypertension; Brain Diseases; Frontotemporal Lobar Degeneration; Dementia; Neurocognitive Disorders

Central Study Contacts

Fabio Moda, phd

CONTACT

0223942770; fabio.moda@istituto-besta.it

Arianna Ciullini, phd

CONTACT

0223942249; arianna.ciullini@istituto-besta.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2025
• First Posted: March 4, 2025
• Study Start: February 27, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF

Locations

IT (4)