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An Amyloid beta (Abeta) vaccine that safely drives immunity to a key pathological species in Alzheimer’s disease: pyroglutamate Abeta

M. Vukicevic, E. Fiorini, S. Siegert, R. Carpintero, M. Rincon, P. Lopez-Deber, N. Piot, M. Ayer, I. Rentero, C. Babolin, S. Bravo-Veyrat, V. Giriens, C. Morici, M. Beuzelin, A. Gesbert, S. Rivot, S. Depretti, P. Donati, J. Streffer, A. Pfeifer, M. H. Kosco-Vilbois

Preclinical results of our wholly owned anti-Abeta vaccine program ACI-24 show that the optimized formulation generates a potent and sustained immune response. Antibodies showed binding to pyroglutamate Abeta, a highly neurotoxic form of Abeta, which, following recent proof-of-concept from a monoclonal antibody, is a promising target for Alzheimer therapy.

Brain Communications, https://doi.org/10.1093/braincomms/fcac022

Published: 04 February 2022

AC Immune's scientific publications

20/02/2023 Afroz T et al., Neurobiology of Disease, 2023

Immunotherapy targeting the C-terminal domain of TDP-43 decreases neuropathology and confers neuroprotection in mouse models of ALS/FTD

Afroz T, Chevalier E, Audrain M, Dumayne C, Ziehm T, Moser R, Egesipe AL, Mottier L, Ratnam M, Neumann M, Havas D, Ollier R, Piorkowska K, Chauhan M, Silva AB, Thapa S, Stöhr J, Bavdek A, Eligert V, Adolfsson O, Nelson PT, Porta S, Lee VMY, Pfeifer A, Kosco-Vilbois M, Seredenina T  
24/12/2022 Njavro JR et al., Cells, 2023, 12, 79

Beneficial Effect of ACI-24 Vaccination on Aβ Plaque Pathology and Microglial Phenotypes in an Amyloidosis Mouse Model

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09/05/2022 Rafii M et al., JAMA Neurology, 2022

Safety, Tolerability, and Immunogenicity of the ACI-24 Vaccine in Adults With Down Syndrome: A Phase 1b Randomized Clinical Trial

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04/02/2022 Vukicevic M et al., Brain Communications, 2022

An Amyloid beta (Abeta) vaccine that safely drives immunity to a key pathological species in Alzheimer’s disease: pyroglutamate Abeta

Vukicevic M, Fiorini E, Siegert S, Carpintero R, Rincon M, Lopez-Deber P, Piot N,  Ayer M, Rentero I, Babolin C, Bravo-Veyrat S, Giriens V, Morici C, Beuzelin M, Gesbert A, Rivot S, Depretti S, Donati P, Streffer J, Pfeifer A, Kosco-Vilbois MH
15/12/2021 Kroth H et al., Bioorg. Med. Chem., 2021

Structure-activity relationship around PI-2620 highlights the importance of the nitrogen atom position in the tricyclic core

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29/08/2021 Kroth H et al., J. Med. Chem. 2021

PI-2620 lead optimization highlights the importance of off-target assays to develop a pet tracer for the detection of pathological aggregated tau in Alzheimer’s disease and other tauopathies

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12/05/2021 Ayalon G et al., Sci. Transl. Med., 2021

Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease

Ayalon G, Lee S-H, Adolfsson O, Foo-Atkins C, Atwal JK, Blendstrup M,  Booler H, Bravo J, Brendza R, Brunstein F, Chan R, Chandra P, Couch JA, Datwani A, Demeule B, DiCara D, Erickson R, Ernst JA, Foreman O, He D, Hötzel I, Keeley M, Kwok MCM, Lafrance-Vanasse J, Lin H, Lu Y,  Luk W, Manser P, Muhs A, Ngu H, Pfeifer A, Pihlgren M, Rao GK, Scearce-Levie K, Schauer SP, Smith WB, Solanoy H, Teng E, Wildsmith KR, Bumbaca Yadav  D, Ying Y, Fuji RN, Kerchner GA
15/10/2020 Gabellieri E et al. , Eur. J. Med. Chem., 2020

Discovery of 2-(4-(2-fluoroethoxy)piperidin-1-yl)-9-methyl-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2014) as PET tracer for the detection of pathological aggregated Tau in Alzheimer's disease and other tauopathies

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11/11/2019 Bullich S et al., J. Nucl. Med., 2019

Evaluation of dosimetry, quantitative methods and test-retest variability of 18F-PI-2620 PET for the assessment of Tau deposits in the human brain

Bullich S, Barret O, Constantinescu C, Sandiego C, Mueller A, Papin C, Perrotin A, Koglin N, Kroth H, Pfeifer A, Madonia J, Seiby JP, Marek K, de Santi, Dinkelborg LM, Berndt M, Tamagnan G, Stephens AW
11/11/2019 Mueller A et al., J. Nucl. Med., 2019

Tau PET imaging with 18F-PI-2620 in patients with Alzheimer's disease and healthy controls: a first-in-human study

Mueller A, Bullich S, Barret O, Madonia J, Berndt M, Papin C, Perrotin A, Koglin N, Kroth H, Pfeifer A, Tamagnan G, Seibyl JP, Marek K, de Santi S, Dinkelborg LM, Stephens AW
20/09/2019 Sreenivasachary N et al., Org. Process Res. Dev., 2019

A Short Synthesis of the 2-Bromo-N,9-dimethyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indol-6-amine Building Block

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01/07/2019 Kroth H et al., Eur. J. Nucl. Med. Mol. Imaging , 2019

Discovery and preclinical characterization of [18F]PI-2620, a next-generation tau PET tracer for the assessment of tau pathology in Alzheimer’s disease and other tauopathies

Kroth H, Oden F, Molette J, Schieferstein H, Capotosti F, Mueller A, Berndt M, Schmitt-Willich H, Darmency V, Gabellieri E, Boudou C, Juergens T, Varisco Y, Vokali E, Hickman DT, Tamagnan G, Pfeifer A, Dinkelborg L, Muhs A, Stephens AW
13/11/2018 Chen H-H et al., Scientific Reports, 2018

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Motifs in the tau protein that control binding to microtubules and aggregation determine pathological effects

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15/03/2017 Sreenivasachary N et al., Bioorganic & Medicinal Chemistry Letters, 2017

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02/11/2016 Theunis C et al., J. Alzheimer. Dis., 2016

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09/08/2016 Lee S-H et al., Cell Reports, 2016

Antibody-mediated targeting of Tau in vivo does not require effector function and microglial engagement

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15/07/2016 Kroth H et al., Bioorganic & Medicinal Chemistry Letters, 2016

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Froestl W, Muhs A, Pfeifer A
25/03/2014 Froestl W et al., Journal of Alzheimer's disease, 2014

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Froestl W, Muhs A, Pfeifer A
21/10/2013 Papassotiropoulos A et al., PNAS, 2013

Human genome-guided identification of memory-modulating drugs

Papassotiropoulos A, Gerhards C, Heck A, Ackermann S, Aerni A, Schicktanz N, Auschra B, Demougin P, Mumme E, Elbert T, Ertl V, Gschwind L, Hanser E, Huynh KD, Jessen F, Kolassa IT, Milnik A, Paganetti P, Spalek K, Vogler C, Muhs A, Pfeifer A, de Quervain DJ
23/08/2013 Koers E et al., Angewandte Chemie International Edition, 2013

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19/08/2013 Theunis C et al., PLoS One, 2013

Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy

Theunis C, Crespo-Biel N, Gafner V, Pihlgren M, Lopez-Deber P, Reis P, Hickman D, Adolfsson O, Chuard N, Mlaki Ndao D, Borghgraef P, Devijver H, Van Leuven F, Pfeifer A, Muhs A
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06/02/2013 Froestl W et al., Journal of Alzheimer's disease, 2013

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Froestl W, Muhs A, Pfeifer A
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Pihlgren M, Silva AB, Madani R, Giriens V, Waeckerle-Men Y, Fettelschloss A, Hickman D, Lopez-Deper MP, Mlaki Ndao D, Vukicevic M, Bucarello AL, Gafner V, Chuard N, Reis P, Piorkowska K, Pfeifer A, Kündig TM, Muhs A, Johansen P
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15/08/2022 Capotosti F et al., AAIC 2022

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18/03/2022 Smith R et al., AD/PDTM 2022

Initial scans using [18F]ACI-12589, a novel PET-tracer for a-synuclein

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Discovery of [18F]ACI-12589, a novel and promising PET-tracer for a-synuclein

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15/03/2022 Seredenina T et al., AD/PDTM 2022

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15/03/2022 Afroz T et al., AD/PDTM 2022

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