Comprehensive Biomarker Profiling of the IFN-α Pathway in Amyotrophic Lateral Sclerosis Patient Biofluids

NCT07260981 | Completed

• 1 other identifier: UNL074
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

ALS is characterized by significant genetic, clinical, and biological heterogeneity. The heritability of ALS is approximately 50%, and variants in more than 200 genes have been associated with the disease. Clinical features are highly variable for most variants, likely due to interactions with other modifier genes and environmental factors. Mutations in groups of genes belonging to specific ALS pathomechanisms may be associated with distinct phenotypes, but better correlations with clinical and biomarker profiles are still needed. Clinically, patients show significant variability in disease onset and progression, as well as in motor and cognitive phenotypes. Several clinical, neurophysiological, neuropsychological, and neuroradiological measures have been developed to account for this variability, but neurochemical biomarkers may represent an ideal tool to identify homogeneous patient subgroups. The most extensively studied neurochemical biomarkers in ALS are neurofilaments, which are released from degenerating motor neurons into biological fluids and have diagnostic and prognostic value. Other potential biomarkers of neuronal damage in ALS include tau (associated with shorter survival), UCHL1, and TDP-43 (both elevated in ALS patients). Microglial and astrocytic involvement in ALS pathogenesis can be investigated by measuring MCP-1 and GFAP, respectively. Considering the growing evidence implicating IFN-alpha involvement in ALS pathogenesis, we aim to comprehensively profile cytokines, neuroinflammatory markers, and analytes related to neurodegeneration in the plasma and cerebrospinal fluid (CSF) of clinically characterized ALS patients and matched healthy controls. This study will support the validation of IFN-alpha pathway activation as a therapeutic target and explore its association with disease phenotype and progression. Furthermore, correlations between biomarker levels and available clinical data will provide insights into potential diagnostic and prognostic biomarkers for ALS, thereby facilitating future therapeutic development.

Conditions

ALS - Amyotrophic Lateral Sclerosis

Keywords

ALS; Nf-L; GFAP; pTau (T181)

Outcome Measures

Primary Outcomes (1)

• Profiling of neurodegenerative and inflammatory markers in in ALS plasma and CSF

  Ulysses Neuroscience Ltd. will perform electrochemiluminescence sandwich ELISA using the Meso-Scale Discovery platform (MESO QuickPlex SQ 120 instrument and analyzed by Discovery Workbench 4.0 software). Data will be analysed as ALS vs healthy control as raw values of each analyte in the samples (pg/mL) and graphed using GraphPad Prism v.9. Specific analytes to be measured include: IFN-α2a, IFN-β, IL-12/IL-23p40, CXCL10/IP10, CCL2/MCP1, IFN-γ, IL-6, IL-8, IL-13, TNF-α, CCL5/RANTES, TDP-43, GFAP, Neurofilament L, Tau \[Total\], pTau T181, pTau T217, pTau T231

  As it is a retrospective study and only biomarker analyses will take place, we plan to start the analysis in October and conclude it in December 2025.

Study Arms (2)

ALS patients

ALS patients, diagnosed accordingly to the revised El Escorial Criteria

Healthy controls

Subjects without a diagnosis of neurodegenerative disease or neuromuscular disorder.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. 30 ALS patients - 30 healthy controls 2. \> 18 years old 3. Age- and sex-matched controls 4. Inclusion/Exclusion criteria (see above) 5. ALS patients have been recruited and blood samples collected by Angelo Quattrini's team (UO neurology, UO Experimental pathology-INSPE) 6. Healthy control samples were purchased from BioIVT.

You may qualify if:

• Age equal or over 18 years old
• ALS patients, diagnosed accordingly to the revised El Escorial Criteria Disease duration \<24 months from symptom onset.
• Age equal or over 18 years old
• Subjects without a diagnosis of neurodegenerative disease or neuromuscular disorder.

You may not qualify if:

• FVC \<60%;
• nutritional or respiratory failure; Significant hepatic or chronic renal failure or any intervening infective (pneumonia, flu-like syndromes, urinary tract infections) or metabolic (acute renal failure, hyperosmolar hyperglycaemic state, severe hyponatremia) conditions present at the time of assessment that could potentially affect biomarker levels.
• ALS patients exhibiting any of these conditions at the time of biofluid sampling as per the Case Report From (CRF) will be excluded from sample selection.
• Significant hepatic or chronic renal failure or any intervening infective (pneumonia, flu-like syndromes, urinary tract infections) or metabolic (acute renal failure, hyperosmolar hyperglycaemic state, severe hyponatremia) conditions present at the time of assessment that could potentially affect biomarker levels.
• Controls exhibiting any of these conditions at the time of biofluid sampling as per the Case Report From (CRF) will be excluded from sample selection.

Sponsors & Collaborators

• Ulysses Neuroscience LTD: lead

Study Sites (1)

Pioneer Life Sciences Cherrywood

Dublin, Ireland

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma and CSF

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

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

Study Officials

• Massimiliano Bianchi

  Ulysses Neuroscience LTD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: October 1, 2025
• First Posted: December 3, 2025
• Study Start: March 1, 2023
• Primary Completion: January 18, 2025
• Study Completion: January 18, 2025
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)