RecruitingNCT06803784

Discovery and Validation of Protein Structural Complexes in Circulating Biofluids As Novel Biomarkers for Early Diagnosis, Prognosis and Therapeutic Management of Patients Affected by Neurodegenerative Disorders

Sponsor

Neuromed IRCCS

Enrollment

110 participants

Start Date

Feb 4, 2025

Study Type

OBSERVATIONAL

Conditions

Parkinson Disease Amyotrophic Lateral Sclerosis(ALS)Alzheimer&Amp;#39;s Disease (AD)Frontotemporal Dementia (FTD)

Summary

Neurodegenerative disorders (NDDs), such as Parkinson¿s disease (PD), Alzheimer¿s disease (AD), Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are characterized by aggregation and intracellular accumulation of misfolded proteins, which are believed to play a key role in synaptic dysfunction and neuronal death. Protein structural complexes in biofluids have been proposed to mirror pathological conditions suggesting their use as biomarkers for NDDs characterized by protein aggregation. In this framework, we plan to: i) collect a large cohort of NDD and prodromal patients and healthy subjects using standardized clinical and genetics procedures; ii) apply a novel method based on genomics, proteomics and bioinformatic analysis to map protein complexes in biofluids; iii) identify novel circulating biomarkers and correlate them to genetic profiling and disease endophenotypes, and; iv) validate the biological properties in human brain tissue and dopaminergic cultures.

Eligibility

Min Age: 20 Years

Plain Language Summary

Simplified for easier understanding

This study is searching for new protein-based biomarkers in blood and cerebrospinal fluid that could allow earlier and more accurate diagnosis of Parkinson's disease and other neurodegenerative conditions — potentially replacing or supplementing current diagnostic tools. **You may be eligible if...** - You have been diagnosed with Parkinson's disease showing at least 2 of the 4 classic symptoms (tremor, rigidity, slowness, asymmetric onset), including tremor or slowness - You have responded to levodopa (a standard Parkinson's medication) during a test dose - You are willing to provide blood or fluid samples as part of routine care **You may NOT be eligible if...** - You have atypical features suggesting a different diagnosis (such as very early balance problems, hallucinations, or rapid cognitive decline) - You have other conditions that could explain your symptoms - You are unable to give consent Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

GENETICGenetic: whole genome sequencing

Genetic: whole genome sequencing PD Partecipants will be assessed for disease progression: Stadio di Hoehn and Yahr, MDS-UPDRS part III, MOCA test, no motor symptoms, therapy and LID occurrence, Sleep disorders. Partecipants will be subjected to peripheral blood sampling for the purification of DNA, plasma, serum, PBMC and generation of hiPSC. DNA of each partecipants we will analysed by whole genome sequencing by next generation sequencing to identify any variant in candidate PD genes

GENETICwhole exome sequencing

Genetic: whole genome sequencing AD Partecipants will be assessed for disease progression: * assessment of cognitive disorders (MMSE, MOCA test, clock test); * assessment of language disorders; * current drug therapy (and possible start date of treatment); * date of onset of cognitive disorders; * acquisition and assessment of imaging data where present (MRI, CT, PET). DNA of each partecipants we will analysed by whole genome sequencing by next generation sequencing to identify any variant in candidate AD genes

GENETICwhole exome sequencing

Genetic: whole genome sequencing ALS/FTD Partecipants will be assessed for disease progression: * clinical classification according to El Escorial - revised; * assessment of cognitive disorders (and classification according to Strong criteria, 2017); * assessment of language disorders; * ongoing pharmacological therapy (and possible start date of treatment); * date of onset of motor and cognitive disorders; * acquisition and assessment of imaging data where present (MRI, CT, PET). DNA of each partecipants we will analysed by whole genome sequencing by next generation sequencing to identify any variant in candidate ALS/FTD genes