Special LMNN SEMINAR // “Biomarkers in Parkinson’s disease”
Event details
| Date | 26.01.2017 |
| Hour | 09:00 › 10:00 |
| Speaker | Brit Mollenhauer, Paracelsus-Elena-Klinik Kassel, Kassel, Germany |
| Location | |
| Category | Conferences - Seminars |
Many fundamental decisions in medicine rely on biomarker, to signal the risk of developing a disease (marker of trait), to indicate manifestation of the disease (marker of state), to monitor the speed of its progression and response to therapy (marker of rate), and to predict its course (marker of fate). The modality of a biomarker ranges from e.g. a clinical measure or a functional test, to biological fluid markers and imaging markers.
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting more than 5 million people worldwide. PD is a highly complex multifactorial disease characterized by a heterogeneous clinical manifestation and variable progression. The diagnosis of PD is largely clinically based with low sensitivity and specificity, especially in the first five years of clinical diagnosis. A major challenge in the field is the lack of insight into the exact underlying biologic mechanisms; thus only symptomatic treatments are available and a neuroprotective approach is lacking. The prevalence of PD is expected to increase dramatically over the next years as the population ages.[1] The field of PD research will greatly benefit from the knowledge of relevant, disease-specific biomarkers in including accepted, easily practiced and validated assays for the quantification as diagnostic and progression biomarker as well as markers to identify subjects at risk to develop PD.
Due to the heterogeneity at the neuropathological level, even when diagnosed as a ‘typical parkinsonian syndrome’ in the clinic by a movement disorder expert a single biomarker is unlikely to correctly identify all forms of parkinsonism. Furthermore, a single laboratory value is unlikely to function as a specific and sensitive indicator trait, state, rate and fate. Optimally different marker modalities (biofluids and structural/functional imaging as in AD research) need to be combined.
As a first step we have shown that intracellular α-synuclein (aSyn), a key protein in PD pathogenesis, is released to the extracellular space and quantification of total aSyn can be useful as diagnostic biomarker in extracellular cerebrospinal fluid (CSF) for PD, shown in different independent cohorts. The clinical diagnostic utility of total aSyn has been limited for a number of reasons, including the finding that changes in the level of total aSyn in PD patients vs. healthy controls are modest, as shown in the multicenter Parkinson Progression Marker Initiative [2]. Therefore there is a need to explore and validate new marker candidates for PD. We have therefore established a new cohort (DeNoPa cohort) of 159 at enrollment recently diagnosed and still drug naïve PD patients and 110 healthy controls and established an algorithm for the improved diagnosis for PD [3]. Following this cohort biannually we explored multimodal progression markers [4]. CSF aSyn is longitudinally in the first two years after the clinical diagnosis relatively stable [4] [5] and to explore the possibly more active phase of the disease before the onset of motor symptoms we extended the DeNoPa cohort to premotor subjects with idiopathic REM sleep behavior disorder (RBD).
Our investigations include clinical investigations, imaging and biochemically in biological fluids untargeted proteome analysis, targeted proteome in search of posttranslational forms of aSyn, metabolome, microbiome and genome analyses.
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting more than 5 million people worldwide. PD is a highly complex multifactorial disease characterized by a heterogeneous clinical manifestation and variable progression. The diagnosis of PD is largely clinically based with low sensitivity and specificity, especially in the first five years of clinical diagnosis. A major challenge in the field is the lack of insight into the exact underlying biologic mechanisms; thus only symptomatic treatments are available and a neuroprotective approach is lacking. The prevalence of PD is expected to increase dramatically over the next years as the population ages.[1] The field of PD research will greatly benefit from the knowledge of relevant, disease-specific biomarkers in including accepted, easily practiced and validated assays for the quantification as diagnostic and progression biomarker as well as markers to identify subjects at risk to develop PD.
Due to the heterogeneity at the neuropathological level, even when diagnosed as a ‘typical parkinsonian syndrome’ in the clinic by a movement disorder expert a single biomarker is unlikely to correctly identify all forms of parkinsonism. Furthermore, a single laboratory value is unlikely to function as a specific and sensitive indicator trait, state, rate and fate. Optimally different marker modalities (biofluids and structural/functional imaging as in AD research) need to be combined.
As a first step we have shown that intracellular α-synuclein (aSyn), a key protein in PD pathogenesis, is released to the extracellular space and quantification of total aSyn can be useful as diagnostic biomarker in extracellular cerebrospinal fluid (CSF) for PD, shown in different independent cohorts. The clinical diagnostic utility of total aSyn has been limited for a number of reasons, including the finding that changes in the level of total aSyn in PD patients vs. healthy controls are modest, as shown in the multicenter Parkinson Progression Marker Initiative [2]. Therefore there is a need to explore and validate new marker candidates for PD. We have therefore established a new cohort (DeNoPa cohort) of 159 at enrollment recently diagnosed and still drug naïve PD patients and 110 healthy controls and established an algorithm for the improved diagnosis for PD [3]. Following this cohort biannually we explored multimodal progression markers [4]. CSF aSyn is longitudinally in the first two years after the clinical diagnosis relatively stable [4] [5] and to explore the possibly more active phase of the disease before the onset of motor symptoms we extended the DeNoPa cohort to premotor subjects with idiopathic REM sleep behavior disorder (RBD).
Our investigations include clinical investigations, imaging and biochemically in biological fluids untargeted proteome analysis, targeted proteome in search of posttranslational forms of aSyn, metabolome, microbiome and genome analyses.
Practical information
- Informed public
- Free
Organizer
- Laboratory of Molecular and Chemical Biology of Neurodegeneration (LMNN) Host : H. Lashuel