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1.144 PARKINSON SUMMER SCHOOL III, WARSAW JULY 2011
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Monday, 12 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S1–S79
experiments show that co use of some serotonergic compounds may be useful in extending therapeutics in schizophrenia and Parkinson’s disease. 1.142 COST ANALYSIS OF THE TREATMENTS FOR PATIENTS WITH COMPLICATED PARKINSON’S DISEASE: SCOPE STUDY F. Valldeoriola1 , J. Puig-Junoy2 , R. Puig-Peiro´ 2,3 , P. Gonzalez ´ 4, Workgroup of the SCOPE Study. 1 Neurology Services; Movement Disorders Unit, Hospital Clinic i Provincial, 2 Centre de Recerca en Economia i Salut (CRES-UPF), Pompeu Fabra University, Barcelona, Spain; 3 Office of Health Economics, London, UK; 4 Health Economics & Reimbursement Dept, Medtronic Ib´erica S.A., Madrid, Spain Introduction: Three therapeutic options exist for Complicated Parkinson’s Disease (CPD): deep brain stimulation (DBS), continuous duodenal levodopa-carbidopa Infusion (CDLCI) and continuous subcutaneous apomorphine infusion (CSAI). This is the first economic analysis to compare the costs of the three therapies, offering payers and physicians useful information to support the decision making in CPD. Methods: Spanish national healthcare system resources consumption was measured with a Healthcare Resources Questionnaire (nine CPD centres). Unit costs (Euro-Spain 2010) were applied in a microcosting approach to obtain the average total cost for each therapy over 5 years. Results: Mean cumulative 5-year cost per patient was significantly lower with DBS (€88,014) versus CSAI (€141,393) and CDLCI (€233,986) (p < 0.0001). DBS was associated with the lowest cumulative costs from year 2, with a yearly average cost of €17,603 versus €46,797 for CDLCI (p = 0.001) and €28,279 for CSAI (p = 0.008). The initial DBS investment (32.2% of the total 5-year costs) was offset by decreases in antiparkinsonian drugs and followup costs. CDLCI and CSAI required constant drug use (i.e. levodopa and carbidopa for CDLCI, apomorphine for CSAI), representing around 95% of their total 5-year cost. Conclusions: Despite being perceived as costly, the initial DBS investment was offset at year 2 by reductions in the ongoing consumption of antiparkinsonian medication. For every patient treated annually with CDLCI, two could be treated with DBS (or €29,194 could be saved) and for every patient treated with CSAI, €10,676 could be saved with DBS. Overall, CDLCI and CSAI require more use of health resources, mostly pharmacological. 1.143 DEVELOPMENT OF A TIME-RESOLVED FRET IMMUNOASSAY FOR a-SYNUCLEIN QUANTIFICATION SUITABLE FOR CLINICAL SAMPLE ANALYSIS AND HIGH-THROUGHPUT TRANSLATIONAL RESEARCH M. Bidinosti1 , D. Shimshek1 , M. Schlossmacher2 , A. Weiss1 . 1 Neuroscience Discovery, Novartis Institutes for BioMedical Research, Basel, Switzerland; 2 OHRI-Neuroscience, University of Ottawa, Ottawa, ON, Canada a-Synuclein is intimately linked to the pathophysiology of Parkinson’s Disease as it is the principle component Lewy bodies and Lewy neurites found in the PD brain. Importantly, missense mutations and multiplication of the a-synuclein (SNCA) locus give way to famial forms of PD with high penetrance. Recent studies suggest that altered levels of a-synuclein in cerebrospinal fluid (CSF) may serve as a proximal disease marker for lewy-body positive forms of PD. However, cross-comparison of the reported absolute a-synuclein levels in the CSF of PD patients shows a ~100-fold difference between studies, likely due to differences in the quantification technology and variations in detection protocols. We developed a sensitive and robust assay based on the use of Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) to quantify a-synuclein levels in biological samples. This method relies on the simultaneous binding of two fluorophore-conjugated monoclonal antibodies to C-terminal a-synuclein epitopes, followed
by coincident energy transfer and fluorescence upon excitation. We optimized assay conditions and determined the Limit of Detection (LoD) (0.07 pg/ml) and dynamic range (0.07–50 pg/ml). The method was verified on CSF samples of a-synuclein transgenic, wild type and knock-out mice for specificity. Notably, the assay requires 10fold less sample volume (5 ml) than previous methods and involves only two pipetting steps, thus minimizing processing time. The assay has been applied to PD patient CSF samples to assess the biomarker potential of a-synculein. Further, given the suitability of this homogeneous assay to drug discovery applications, it was adapted to a high-throughput siRNA library screening format with the aim of identifying genetic regulators of a-synuclein expression levels. Control experiments demonstrated an excellent ‘screening window’, thus a pilot screen of a focused siRNA library was undertaken. Replicate screens exhibited good concordance and preliminary hits were selected for re-testing. A reduced hit-list was then compiled based on changes of alpha-synuclein level by1 SD (or 25%) and confirmation by a second TR-FRET assay (unique antibody pair). Hit triaging is ongoing. It is anticipated that this work will identify cellular mechanisms that control a-synuclein levels and which may be exploited for the development of novel PD therapies. 1.144 PARKINSON SUMMER SCHOOL III, WARSAW JULY 2011 M. Maliia1 , P. de Roos2 . 1 University of Medicine and Pharmacy, ‘Carol Davila’, Bucharest, Bucharest, Romania; 2 Neurology, L¨ anssjukhuset Ryhov, J¨ onk¨ oping, Sweden Parkinson Summer School is an original, creative approach to the education into the field of Neurology, more precisely Parkinson Disease combined with Human Skills training, initiated by Paul de Roos and Krzysztof Nesterowicz. Already at its third edition, it invites medical and non-medical students who have a connection with this pathology (psychologist, social scientists, physical therapists) to interact for 9 days and come up with an original idea of research that could bring light into the current view over this debilitating disease. Based on our preferences and our previous knowledge we segregated into 3 groups that tackled different problems, meaning Pathophysiology, Pharmaceutical Treatment and Psycho-Social Aspects. The first author of this poster took part in the first group and proposed and presented in front of Prof. Dr. E. Wolters (Netherlands) and Prof. Dr. H. Steinbusch (Netherlands) “Investigation of the Neurofunctional Substrates behind Preserved Bicycling Abilities in Parkinsons Disease Patients with Severe Gait Disturbances”. Our idea was highly appreciated and commented upon in the end. During the congress, the concepts as well as the potential educational role of the summer school was discussed, and it was agreed upon that such translational programs could play an essential role in the further professionalisation of younger doctors and scientists.
Related Disorders 1.201 CLINICAL FEATURES AND DIFFERENTIATION OF ATYPICAL PARKINSONIAN SYNDROMES L. Chen1 , B. Zhang2 . 1 Neurology Department, Tianjin Neurological Central (Huanhu) Hospital, 2 Tianjin Medical University General Hospital, Tianjin, China Objective: To explore the clinical features and differentiation of atypical Parkinsonian Syndromes. Methods: 73 IPD patients, 68 MSA patients, 10 DLB patients, 15 PSP patients and 6 CBD patients were incruited between January 1, 2004 and April 30, 2009 from neurology department of Tianjin general hospital and Tianjin Huan Hu Hospital. All patients were given detailed investigation, physical examination, mini-mental
Monday, 12 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S1–S79
experiments show that co use of some serotonergic compounds may be useful in extending therapeutics in schizophrenia and Parkinson’s disease. 1.142 COST ANALYSIS OF THE TREATMENTS FOR PATIENTS WITH COMPLICATED PARKINSON’S DISEASE: SCOPE STUDY F. Valldeoriola1 , J. Puig-Junoy2 , R. Puig-Peiro´ 2,3 , P. Gonzalez ´ 4, Workgroup of the SCOPE Study. 1 Neurology Services; Movement Disorders Unit, Hospital Clinic i Provincial, 2 Centre de Recerca en Economia i Salut (CRES-UPF), Pompeu Fabra University, Barcelona, Spain; 3 Office of Health Economics, London, UK; 4 Health Economics & Reimbursement Dept, Medtronic Ib´erica S.A., Madrid, Spain Introduction: Three therapeutic options exist for Complicated Parkinson’s Disease (CPD): deep brain stimulation (DBS), continuous duodenal levodopa-carbidopa Infusion (CDLCI) and continuous subcutaneous apomorphine infusion (CSAI). This is the first economic analysis to compare the costs of the three therapies, offering payers and physicians useful information to support the decision making in CPD. Methods: Spanish national healthcare system resources consumption was measured with a Healthcare Resources Questionnaire (nine CPD centres). Unit costs (Euro-Spain 2010) were applied in a microcosting approach to obtain the average total cost for each therapy over 5 years. Results: Mean cumulative 5-year cost per patient was significantly lower with DBS (€88,014) versus CSAI (€141,393) and CDLCI (€233,986) (p < 0.0001). DBS was associated with the lowest cumulative costs from year 2, with a yearly average cost of €17,603 versus €46,797 for CDLCI (p = 0.001) and €28,279 for CSAI (p = 0.008). The initial DBS investment (32.2% of the total 5-year costs) was offset by decreases in antiparkinsonian drugs and followup costs. CDLCI and CSAI required constant drug use (i.e. levodopa and carbidopa for CDLCI, apomorphine for CSAI), representing around 95% of their total 5-year cost. Conclusions: Despite being perceived as costly, the initial DBS investment was offset at year 2 by reductions in the ongoing consumption of antiparkinsonian medication. For every patient treated annually with CDLCI, two could be treated with DBS (or €29,194 could be saved) and for every patient treated with CSAI, €10,676 could be saved with DBS. Overall, CDLCI and CSAI require more use of health resources, mostly pharmacological. 1.143 DEVELOPMENT OF A TIME-RESOLVED FRET IMMUNOASSAY FOR a-SYNUCLEIN QUANTIFICATION SUITABLE FOR CLINICAL SAMPLE ANALYSIS AND HIGH-THROUGHPUT TRANSLATIONAL RESEARCH M. Bidinosti1 , D. Shimshek1 , M. Schlossmacher2 , A. Weiss1 . 1 Neuroscience Discovery, Novartis Institutes for BioMedical Research, Basel, Switzerland; 2 OHRI-Neuroscience, University of Ottawa, Ottawa, ON, Canada a-Synuclein is intimately linked to the pathophysiology of Parkinson’s Disease as it is the principle component Lewy bodies and Lewy neurites found in the PD brain. Importantly, missense mutations and multiplication of the a-synuclein (SNCA) locus give way to famial forms of PD with high penetrance. Recent studies suggest that altered levels of a-synuclein in cerebrospinal fluid (CSF) may serve as a proximal disease marker for lewy-body positive forms of PD. However, cross-comparison of the reported absolute a-synuclein levels in the CSF of PD patients shows a ~100-fold difference between studies, likely due to differences in the quantification technology and variations in detection protocols. We developed a sensitive and robust assay based on the use of Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) to quantify a-synuclein levels in biological samples. This method relies on the simultaneous binding of two fluorophore-conjugated monoclonal antibodies to C-terminal a-synuclein epitopes, followed
by coincident energy transfer and fluorescence upon excitation. We optimized assay conditions and determined the Limit of Detection (LoD) (0.07 pg/ml) and dynamic range (0.07–50 pg/ml). The method was verified on CSF samples of a-synuclein transgenic, wild type and knock-out mice for specificity. Notably, the assay requires 10fold less sample volume (5 ml) than previous methods and involves only two pipetting steps, thus minimizing processing time. The assay has been applied to PD patient CSF samples to assess the biomarker potential of a-synculein. Further, given the suitability of this homogeneous assay to drug discovery applications, it was adapted to a high-throughput siRNA library screening format with the aim of identifying genetic regulators of a-synuclein expression levels. Control experiments demonstrated an excellent ‘screening window’, thus a pilot screen of a focused siRNA library was undertaken. Replicate screens exhibited good concordance and preliminary hits were selected for re-testing. A reduced hit-list was then compiled based on changes of alpha-synuclein level by1 SD (or 25%) and confirmation by a second TR-FRET assay (unique antibody pair). Hit triaging is ongoing. It is anticipated that this work will identify cellular mechanisms that control a-synuclein levels and which may be exploited for the development of novel PD therapies. 1.144 PARKINSON SUMMER SCHOOL III, WARSAW JULY 2011 M. Maliia1 , P. de Roos2 . 1 University of Medicine and Pharmacy, ‘Carol Davila’, Bucharest, Bucharest, Romania; 2 Neurology, L¨ anssjukhuset Ryhov, J¨ onk¨ oping, Sweden Parkinson Summer School is an original, creative approach to the education into the field of Neurology, more precisely Parkinson Disease combined with Human Skills training, initiated by Paul de Roos and Krzysztof Nesterowicz. Already at its third edition, it invites medical and non-medical students who have a connection with this pathology (psychologist, social scientists, physical therapists) to interact for 9 days and come up with an original idea of research that could bring light into the current view over this debilitating disease. Based on our preferences and our previous knowledge we segregated into 3 groups that tackled different problems, meaning Pathophysiology, Pharmaceutical Treatment and Psycho-Social Aspects. The first author of this poster took part in the first group and proposed and presented in front of Prof. Dr. E. Wolters (Netherlands) and Prof. Dr. H. Steinbusch (Netherlands) “Investigation of the Neurofunctional Substrates behind Preserved Bicycling Abilities in Parkinsons Disease Patients with Severe Gait Disturbances”. Our idea was highly appreciated and commented upon in the end. During the congress, the concepts as well as the potential educational role of the summer school was discussed, and it was agreed upon that such translational programs could play an essential role in the further professionalisation of younger doctors and scientists.
Related Disorders 1.201 CLINICAL FEATURES AND DIFFERENTIATION OF ATYPICAL PARKINSONIAN SYNDROMES L. Chen1 , B. Zhang2 . 1 Neurology Department, Tianjin Neurological Central (Huanhu) Hospital, 2 Tianjin Medical University General Hospital, Tianjin, China Objective: To explore the clinical features and differentiation of atypical Parkinsonian Syndromes. Methods: 73 IPD patients, 68 MSA patients, 10 DLB patients, 15 PSP patients and 6 CBD patients were incruited between January 1, 2004 and April 30, 2009 from neurology department of Tianjin general hospital and Tianjin Huan Hu Hospital. All patients were given detailed investigation, physical examination, mini-mental