analysis of the prognostic role of epigenetic biomarkers in relation to the motor decline in parkinson's disease

Conditions: Parkinson Disease

Summary: biogenparkinson is an observational, prospective cohort study evaluating biomarkers of parkinson's disease (pd) progression in community-dwelling subjects aged 65 years or more, consecutively referring to inrca outpatient clinic of the neurology unit. selected patients will undergo clinical and laboratory evaluations at the baseline, and will be followed up after 6 and 12 months. the biological evaluation will include the determination of i) routine biological parameters ii) advanced biomarkers such as epigenetic analysis of dna methylation, genetic analysis on multiple loci associated with pd progression and specific proteins associated with motor and non-motor decline. after obtaining all data, multiple statistical analysis will be performed to evaluate the most accurate prognostic biomarkers of pd progression at this stage of disease.

the objective of the biogenparkinson study is the evaluation of the prognostic accuracy of epigenetic, genetic and protein biomarkers in relation to parkinson's disease (pd) motor symptoms progression (assessed by changes in unified parkinson's disease rating scale part iii (updrs iii)) in biological samples of 103 pd patients aged 65 or more. changes of quality of life (assessed by parkinson's disease questionnaire 39 item (pdq-39)) and cognitive performance (assessed by the mini-mental state examination (mmse)) will be also investigated. the characterization of the pd patients' phenotypes and genotypes will allow the investigation on the predisposition to a severe progression of the disease, in order to early predict the progression of the disease and improving the accuracy of personalized interventions. the evidence collected will inform multidisciplinary and personalized interventions in the future. among the advanced biomarkers that will be evaluated in the study, epigenetic analysis of cpg loci such as cg17445913 in kcnb1 gene, cg02920897 in dleu2 gene and cg01754178 in ptprn2 gene are expected to improve the prognostic accuracy of motor and cognitive decline of pd patients at hoehn and yahr stage ii/iii after 12 months of follow up. genetic analysis in purified genomic dna samples will be performed on multiple loci associated with pd progression such as rs2230288 and rs75548401 in order to confirm their association with motor decline over time, and to assess their association with non-motor decline. protein analysis on bone sialoprotein (bsp), osteomodulin (omd), aminoacylase-1 (acy1), and growth hormone receptor (ghr) will be also evaluated with respect to motor and non-motor decline in pd patients in order to be compared with the other biomarkers. scores on updrs parts iii, obtained by using using the published cut-offs classification of mds-updrs severity, will be drawn at the baseline, at 6-month and at 12-month follow-up visits, in order to assess pd motor progression. additional assessments include demographic and clinical data, parkinson disease questionnaire 39 item (pdq-39) hoehn and yahr stage, mmse, frontal assessment battery (fab), list of disease and medication, falls, functional status, quality of life and socio-economic characteristics.

Eligibility criteria:
inclusion criteria: * pd at hoehn and yahr stage ≤3 * mmse test ≥24 score exclusion criteria: * mmse score \< 24 * severe cardiovascular diseases (including congestive heart failure nyha=4, acute coronary syndrome, stroke) * history of traumatic brain injury, previous deep brain surgery * current substance or alcohol abuse * reduced life expectancy less than six months

Keywords: parkinson disease aging biomarkers dna methylation precision medicine epigenomics genetics disease progression