Differential diagnosis of Parkinson s Disease (PD), Dementia with Lewy Bodies (DLB) & to other neuropathies with Parkinson-like syndromes

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1 Differential diagnosis of Parkinson s Disease (PD), Dementia with Lewy Bodies (DLB) & to other neuropathies with Parkinson-like syndromes Dr. Carlos Güntner on behalf of PD. Dr. Schneider cguntner@sciencebridge.de BioVaria May

2 MBM ScienceBridge GmbH 100% daughter of the Georg-August-Universität Göttingen Public Law Foundation Evaluating, protecting and commercializing academic inventions Geography of license portfolio Serving as technology transfer provider to 9 research institutions -2-

3 The Challenge Currently, no assay or imaging method is available that differentiate between PD, atypic Parkinson syndromes like DLB and to other neuropathies with Parkinson-like syndromes. Early and accurate diagnosis is important because a variety of drugs, including antipsychotic, anticholinergics and some antiparkinsonian medications can for example worsen DLB symptoms. These (wrong) medications can cause severe worsening of movement and a potentially fatal condition known as neuroleptic malignant syndrome (NMS: severe fever, muscle rigidity and breakdown leading to kidney failure). There is a need for methods to differentiate PD, atypic Parkinson syndrome like DLB and other neuropathies with Parkinson-like syndromes! -3-

4 Total -Synuclein A diagnostic biomarker? - Current state Total soluble and aggregated -synuclein was detected in body fluids, such as plasma and CSF. However, conflicting results were reported on the level of total -synuclein compared to controls in CSF and plasma samples. In addition, these conflicting reports had only low sensitivities and specificities to distinguish PD or DLB from non- synuclein related Parkinson syndromes and other neurological controls. Therefore, -synuclein has not been approved as a diagnostic biomarker for clinical applications yet. Our solution: Exosomal -synuclein as a valid diagnostic biomarker! -4-

5 Our solution Scientists at the University of Göttingen, Medical Department developed a new diagnostic approach to differentiate between DLB, PD and other neuropathies by: extracting exosomes from cerebrospinal fluid (CSF patient samples), measuring the amount of exosomal -synuclein, counting number of exosomes, calculating ratio exosomal -synuclein/number of exosomes. -5-

6 Advantages Differential diagnosis based on accepted pathological marker. Robust diagnosis independent of purification protocol by: (a) using pathological sub-population of α-synuclein in exosomes and (b) relating to total number of exosomes in sample. Easy and standardized exosome preparation possible (SEC, density gradient or ultra centrifugation). Differential diagnosis of DLB vs PD with a high sensitivity (>0.85) and high specificity (>0.80) more than twice compared to total CSF α-synuclein. Differential diagnosis of DLB and PD to other neuropathies with Parkinson-like syndromes. Validated on patient's CSF sample in a clinical cohort of >

7 (1) Exosomal -synuclein# & Number of exosomes* Differential diagnosis of DLB & PD. Neurological controls (no PD or dementia): PNP: polyneuropathy (affecting peripheral nerves, symptoms: weakness, numbness, pins-and-needles, burning pain) PSP: progressive supranuclear palsy (affecting part of brain, movement and visual symptoms) analysed by electrochemiluminescence assay (a-syn antibody: MJF-1 clone 12.1, Kruse et al. 2012). * analysed by nanoparticle tracking analysis (NanoSight LM10) # -7-

8 (2) Calculating ratio exosomal -synuclein/exosomes Diagnostic biomarker for DLB & PD & other Neuropathies ratio Differential diagnosis of DLB & PD to other Neuropathies! neurological controls -8-

9 Diagnostic performance of exosomal -synuclein - DLB vs PD Receiver operating characteristic (ROC) curves to determine the diagnostic performance as a diagnostic test. (true positive rate) Exosomal -Synuclein - DLB vs PD (false positive rate) -9-

10 Diagnostic performance of Ratio -Syn/exosomes - PD vs PSP (true positive rate) Ratio -Syn/exosomes - PD vs PSP (false positive rate)

11 Commercial potential Parkinson s disease (PD) is a neurodegenerative disorder with motor symptoms which affects approximately 1% of the population over 65 years. Atypical Parkinson syndrome arise generally from other neurodegenerative diseases like Dementia with Lewy bodies (DLB). Recent studies reporting a prevalence range of DLB up to 22.8% of all dementia cases. The accurate distinction between PD, DLB and other non-αsynuclein variants with Parkinson syndrome is very challenging due to an overlap of both clinical symptoms and neuropathological changes. There is a high unmet need for differential biomarkers!

12 IP & References International PCT patent application: WO A1 Excellent chance for grant of patent: ISR: no X or Y-documents listed! Scientific publication: Stuendl et al.: Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies. Brain 2016; 139(2): We look for a partner to license, develop and commercialize our technology. Thank you for your interest!