Exploration of GCase Activity to Identify a Subpopulation Eligible for a Therapeutic Trial in Dementia with Lewy Bodies
- Conditions
- Dementia with Lewy Bodies
- Interventions
- Diagnostic Test: GlucocerebrosidaseGenetic: GBA gene
- Registration Number
- NCT05304195
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 236
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description DLB patients Glucocerebrosidase Dementia with lewy bodies according to the revised criteria of Mc Keith 2017 DLB patients GBA gene Dementia with lewy bodies according to the revised criteria of Mc Keith 2017 Control Glucocerebrosidase Absence of cognitive impairment and clinical element for a neurodegenerative disease Control GBA gene Absence of cognitive impairment and clinical element for a neurodegenerative disease
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (1)
Centre de neurologie Cognitive
🇫🇷Paris, France