Clinical trial NCT03918616: P2X7 Receptor, Inflammation and Neurodegenerative Diseases
Official title: P2X7 Receptor, Inflammation and Pathophysiology of Neurodegenerative Diseases
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neuro-Degenerative Disease
Keywords: Alzheimer disease
Parkinson disease
P2X7 receptor
Lead sponsor: University of Pisa
Sponsor class: OTHER
First posted: 2019-04-17
Enrollment: 50
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study consecutively enrolled 50 newly-diagnosed, treatment-naive PD or AD individuals among those referring to the Neurology Unit, University Hospital in Pisa, Italy.

Brief summary: Parkinson disease (PD) is a chronic degenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Its pathophysiological mechanisms are still partially unknown; a main role seems to be played by chronic neuroinflammation. A few reports have addressed the possible involvement of the inflammasome in PD, just describing the protective effect of P2X7 purinergic receptor (P2X7R) blockers in murine models of the disease and in microglial cells, where NLRP3 is activated by α-Synuclein, triggering a neuroinflammation that contributes to degeneration of dopaminergic neurons. It is still unclear whether, in addition to the increased brain expression and function of the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing type 3 (NLRP3) inflammasome platform, a systemic activation of such complex might participate in the pathogenesis of PD, which could be the role of the P2X7R in this scenario, and whether such patterns undergo any specific epigenetic regulation. The present study has been designed to address these issues.

Detailed description: The day of the study patientes underwent a complete clinical evaluation and assessment of psycho-physical abilities using specific test such as Mini-Mental State Examination (MMSE), Cognitive Alzheimer's Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS). Blood samples were collected from an antecubital vein to assess serum and plasma aliquots for blood routine analysis and RNA and protein extraction from circulating lymphomonocytes.

To explore a putative epigenetic regulation of such complex scenario some circulating miRNAs likely involved in the pathogenesis of neurological diseases and neuro-inflammation will be measured.

Expression and functional activity of P2X7R-inflammasome complex will be measured by PCR and WB. Acute phase cytokines inflammasome-related levels will be determined by ELISA. Biochemical parameters (fasting glucose, lipid profile, serum creatinine, uric acid) will be measured by standard methods in the biochemistry laboratory of the University Hospital in Pisa. The same determinations will be repeated after one year from the first visit.

Eligibility criteria: Inclusion Criteria:

* newly-diagnosed PD or AD;
* no previous specific treatment;
* no systemic inflammatory or immunological disease and/or cancer;
* no anti-inflammatory drugs assumed in the three months preceding the enrolment;
* patients able to consent.

Exclusion Criteria:

* history of strokes or any neurological disease;
* patients assuming neuroleptic drugs;
* atypical symptoms at onset.

Primary outcomes:
measure: Change from baseline in P2X7R-inflammasome activity
timeFrame: each patient will be assessed one year after diagnosis
measure: Change from baseline in NFkB activity
timeFrame: each patient will be assessed one year after diagnosis
measure: Change from baseline in serum α-synuclein
timeFrame: each patient will be assessed one year after diagnosis
measure: Change from baseline in serum IL-1β
timeFrame: each patient will be assessed one year after diagnosis
measure: Change from baseline in serum IL-18
timeFrame: each patient will be assessed one year after diagnosis
measure: Change from baseline in circulating levels of microRNA miR-30 and miR-7
timeFrame: each patient will be assessed one year after diagnosis
Secondary outcomes:
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: University of Pisa
Study officials:
affiliation: Univeristy of Pisa
name: Anna Solini, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: