Dementia With Lewy Bodies
Conditions
Keywords
Glucocerebrosidase, GBA gene
Brief summary
This research focuses on the activity of an enzymatic protein: glucocerebrosidase, in dementia with lewy bodies (DLB). Indeed, the mutation of the GBA gene responsible for a decrease in the activity of glucocerebrosidase is the most frequent known genetic risk factor in DLB. However, mutations of the GBA gene are known in another pathology, Gaucher disease, in which treatments have been developed. The objective of this research is to determine if glucocerebrosidase activity is decreased in DLB. This hypothesis could open up a therapeutic perspective, with treatments already used in Gaucher disease.
Detailed description
Population: 118 patients and 118 control subjects Act of research: blood test Objectifs : * Comparison of glucocerebrosidase activity between patients and controls * Search for variants or mutations of the GBA gene and correlation with glucocerebrosidase activity * Correlation between clinical characteristics (UPDRS motor scale, MMSE cognitive scale) and GCase activity in patients * Identification of macrophage abnormalities and the impact of treatments targeting the GBA pathway on the deregulation of biomarkers in patient macrophages.
Interventions
DIAGNOSTIC_TESTGlucocerebrosidase
Blood sample (10ml) for GCase activity
GENETICGBA gene
Blood sample (10ml) for variants or mutations of the GBA gene
DIAGNOSTIC_TESTMacrophage biomarkers
Blood sample (20ml) for macrophage biomarkers
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for patients : * Male or female aged ≥ 50 years old * Presence of an accompanying person * Dementia with lewy bodies according to the revised criteria of Mc Keith 2017 Inclusion Criteria for controls: * Male or female aged ≥ 50 years old * Absence of cognitive impairment and clinical element for a neurodegenerative disease
Exclusion criteria
for patients: * Other neurodegenerative disease * Gaucher disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| GCase activity in patients and control by fluorometry | through study competion, an average of 1 year | difference in measurement of glucocerebrosidase enzyme activity (by fluorometry method) between DLB patients and control subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GBA gene and GCase activity | through study competion, an average of 1 year | correlation between the presence of GBA gene mutation and the measurement of glucocerebrosidase enzymatic activity |
| MMSE score and GCase activity | through study competion, an average of 1 year | correlation between the measurement of glucocerebrosidase enzymatic activity and MMSE score (Mini-Mental State Examination from 0-severe to 30-normal) of DLB patients |
| motor sub-score of UPDRS score and GCase activity | through study competion, an average of 1 year | correlation between the measurement of glucocerebrosidase enzymatic activity and motor sub-score of UPDRS score (motor sub-score of Unified Parkinson Disease Rating Scale from) of DLB patients The score is between 0 and 55. The score increases proportionally to the severity of the extrapyramidal syndrome. |
| GBA gene and macrophage abnormalities | through study competion, an average of 1 year | Correlation between the presence of a GBA gene mutation and abnormal macrophage activation reflecting a specific inflammatory profile and biomarker variation. |
| Treatment and macrophage biomarkers | through study competion, an average of 1 year | Identification of the impact of treatments targeting the GBA pathway on the deregulation of biomarkers in macrophages. |
Countries
France
Outcome results
None listed