De-risking R&D of neurodegenerative drugs by versatile biomarker utility

Aggregated proteins are pathological hallmarks of CNS diseases. It is well-established that small oligomers and protofibrils act as the toxic drivers behind these disorders. Consequently, numerous drugs have been formulated to interfere with protein aggregation with the ultimate goal of curing the disease.

sFIDA, endowed with sub-femtomolar sensitivity, can quantify oligomers at the single-particle level. This makes it an invaluable tool in both pre-clinical and clinical applications. These applications include patient selection and stratification, therapy monitoring, and validation of Mechanism of Action (MoA) and target engagement.

How it works

❶ Wells are chemically modified to bind a capture antibody and sample is added.

❷ Both, oligomers and monomers are bound by the capture antibody.

❸ Using the same epitope for capture and detection, only oligomers are probed – but no monomers.

❹ Individual oligomers are detected and counted by highly sensitive fluorescence microscopy.

Aβ aggregate quantification in stool samples

Synthetic Aβ aggregates

Synthetic Aβ aggregates

Aβ aggregates in AD stool samples

Aβ aggregates in AD stool samples

Buffer control

Buffer control

Publications

  • Disrupted-in-schizophrenia 1 protein aggregates in cerebrospinal fluid are elevated in patients with first-episode psychosis

    Pils, M. et al.

    Psychiatry Clin Neurosci (2023) Online ahead of print.

    https://doi.org/10.1111/pcn.13594

  • Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool

    Schaffrath, A. et al.

    NPJ Parkinsons Dis 9, 14 (2023).

    https://doi.org/10.1038/s41531-023-00458-4

  • Development and Implementation of an Internal Quality Control Sample to Standardize Oligomer-Based Diagnostics of Alzheimer’s Disease

    Pils, M. et al.

    Diagnostics (Basel) 13 (2023).

    https://doi.org/10.3390/diagnostics13101702

  • Oral treatment with the all-d-peptide RD2 enhances cognition in aged beagle dogs – A model of sporadic Alzheimer’s disease

    Kutzsche, J. et al.

    Heliyon 9, e18443 (2023).

    https://doi.org/10.1016/j.heliyon.2023.e18443

  • Tau protein aggregation associated with SARS-CoV-2 main protease

    Eberle, R. J. et al.

    PLoS One 18, e0288138 (2023).

    https://doi.org/10.1371/journal.pone.0288138

  • Abeta oligomer concentration in mouse and human brain and its drug-induced reduction ex vivo

    Kass, B. et al.

    Cell Rep Med 3, 100630 (2022).

    https://doi.org/10.1016/j.xcrm.2022.100630

  • Quantitative detection of alpha-Synuclein and Tau oligomers and other aggregates by digital single particle counting

    Blomeke, L. et al.

    NPJ Parkinsons Dis 8, 68 (2022).

    https://doi.org/10.1038/s41531-022-00330-x

  • Abeta Oligomer Elimination Restores Cognition in Transgenic Alzheimer’s Mice with Full-blown Pathology

    Schemmert, S. et al.

    Mol Neurobiol 56, 2211-2223 (2019).

    https://doi.org/10.1007/s12035-018-1209-3

  • Advancements of the sFIDA method for oligomer-based diagnostics of neurodegenerative diseases

    Kulawik, A., Heise, H., Zafiu, C., Willbold, D. & Bannach, O.

    FEBS Lett 592, 516-534 (2018).

    https://doi.org/10.1002/1873-3468.12983

  • Analysis of anticoagulants for blood-based quantitation of amyloid beta oligomers in the sFIDA assay

    Kravchenko, K. et al.

    Biol Chem 398, 465-475 (2017).

    https://doi.org/10.1515/hsz-2016-0153

  • sFIDA automation yields sub-femtomolar limit of detection for Abeta aggregates in body fluids

    Herrmann, Y. et al.

    Clin Biochem 50, 244-247 (2017).

    https://doi.org/10.1016/j.clinbiochem.2016.11.001

  • Nanoparticle standards for immuno-based quantitation of alpha-synuclein oligomers in diagnostics of Parkinson’s disease and other synucleinopathies

    Herrmann, Y. et al.

    Chim Acta 466, 152-159 (2017).

    https://doi.org/10.1016/j.cca.2017.01.010

  • Application of an Amyloid Beta Oligomer Standard in the sFIDA Assay

    Kuhbach, K. et al.,

    Front Neurosci 10, 8 (2016).

    https://doi.org/10.3389/fnins.2016.00008

  • The amyloid-beta oligomer count in cerebrospinal fluid is a biomarker for Alzheimer’s disease.

    Wang-Dietrich, L. et al.,

    J Alzheimers Dis 34, 985-994 (2013).

    https://doi.org:10.3233/JAD-122047

  • Biofunctionalized Silica Nanoparticles: Standards in Amyloid-beta Oligomer-Based Diagnosis of Alzheimer’s Disease

    Hulsemann, M. et al.,

    J Alzheimers Dis 54, 79-88 (2016).

    https://doi.org/10.3233/JAD-160253