Publications

A selection of publications from the management of AlzeCure Pharma:

NeuroRestore

Safety, Tolerability, Pharmacokinetics and Quantitative Electroencephalography Assessment of ACD856, a Novel Positive Allosteric Modulator of Trk-Receptors Following Multiple Doses in Healthy Subjects
Önnestam, K., Nilsson, B., Rother, M. Rein-Hedin E., Bylund J., Anderer P., Kemethofer M., Halldin, M., Sandin J., Segerdahl M. J Prev Alzheimers Dis (2023).

Antidepressant effects of novel positive allosteric modulatorsof Trk receptor mediated signaling – a potential therapeutic concept?
Madjid N, Lidell V, Nordvall G, Lindskog M, Ögren SO, Forsell P, Sandin J. Psychopharmacology 240, 1789–1804 (2023).

Neuroprotective and Disease-Modifying Effects of the Triazinetrione ACD856, a Positive Allosteric Modulator of Trk-Receptors for the Treatment of Cognitive Dysfunction in Alzheimer’s Disease
Parrado Fernandez, C.; Juric, S.; Backlund, M.; Dahlström, M.; Madjid, N.; Lidell, V.; Rasti, A.; Sandin, J.; Nordvall, G.; Forsell, P. Int. J. Mol. Sci. 2023.

Effects on neuroprotection and neuro plasticity by the clinical compound ACD856, a novel positive modulator of Trk-receptors from the NeuroRestore® platform
Authors : Johan Sandin, Sanja Juric, Cristina Parrado-Fernández, Nather Madjid, Gunnar Nordvall, Maria Backlund, Märta Dahlström, and Pontus Forsell.
AD/PD 2023, March 28 – April 1, 2023.

Preclinical characterization of ACD856
Authors : Cristina Parrado-Fernández1, Gunnar Nordvall1, Sanja Juric1, Nather Madjiid1, Maria Backlund1, Märta Dahlström1, Johan Sandin1, Pontus Forsell1
1AlzeCure Pharma AB- Huddinge (Sweden) CTAD 29 nov–2 dec 2022.

Quantitative EEG results from a multiple ascending dose study
Authors : Martin Jönsson1, Kristin Önnestam1, Boel Nilsson1, Matthias Rother1, Erik Rein- Hedin2, Peter Anderer3, Manuel Kemethofer3, Magnus Halldin1, Pontus Forsell1, Gunnar Nordvall1, Johan Sandin1, Märta Segerdahl1.
1AlzeCure Pharma AB- Huddinge (Sweden) 2CTC Clinical Trial Consultants AB- Uppsala (Sweden) 3The Siesta Group Schlafanalyse GmbH- Vienna (Austria) CTAD 29 nov–2 dec 2022.

The Trk-pam Acd856 Improves Mitochondrial Function And Increases Bdnf Levels In Primary Cortical Neurons Cristina Parrado, Sanja Juric, Märta Dahlström1, Johan Sandin, Pontus Forsell,  AlzeCurePharma AB, Hälsovägen7, Huddinge, Sweden.

Neurotrophin targeted therapeutics – a gateway to cognition and more? By Dr. Gunnar Nordvall, Head of Chemistry, Dr. Pontus Forsell, Head of Research and Discovery and Dr. Johan Sandin, CSO, 2022, Aug 16.

Results From a Multiple Ascending Dose Study in Healthy Volunteers of ACD856, a Positive Modulator of Neurotrophin Trk-Receptors, AAIC, July – Aug., 2022
Kristin Önnestam1 MSc, Matthias Rother1 MD, PhD, Erik Rein-Hedin2 MD, Johan Bylund2 PhD, Magnus M Halldin1 PhD, Boel Nilsson1 MSc, Pontus Forsell1 PhD, Gunnar Nordvall1 PhD, Johan Sandin1 PhD, Märta Segerdahl1 MD, PhD. AlzeCure Pharma AB, Hälsovägen 7, Huddinge, Sweden  2. CTC Clinical Trial Consultants AB, Dag Hammarskjölds väg 10B, Uppsala, Sweden.

Characterization of positive allosteric modulators of TrkB for the treatment of depression  Sandin, J., Nordvall, G., Madjid, N., Dahlström, M., Parrado, C., Backlund, M., Lidell, V., Halldin, M. and Forsell, P., ECNP 2021, October 2-5.

ACD856, a novel cognitive enhancer targeting neurotrophin signaling for the treatment of Alzheimer’s Disease  Forsell, P., Halldin, M., Dahlström, M., Madjid, N., Rother, M., Van Es-Johansson, A., Lundkvist, J., Eriksdotter, M., Jönsson, M., Winblad, B. and Sandin, J., CTAD 2020, Nov 4-7.

Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction
Märta Dahlström; Nather Madjid; Gunnar Nordvall; Magnus M. Halldin; Erika Vazquez-Juarez; Maria Lindskog; Johan Sandin; Bengt Winblad; Maria Eriksdotter; Pontus Forsell Cells 2021, Volume 10, Issue 8, 1871.

ACD856 – a novel positive allosteric modulator of Trk-receptors in clinical development for the treatment of Alzheimer’s disease
Nordvall, G., Madjid, N., Backlund, M., Halldin, M., Rother., M., Nilsson, B., Sandin, J.* and Forsell, P., AAIC 2021, July 26-30.

ACD856, a positive modulator of neurotrophin signaling reverses scopolamine- or age-induced cognitive deficits
Pontus Forsell, Gunnar Nordvall, Nather Madjid, Märta Dahlström, Magnus Halldin, Johan Lundkvist, Bengt Winblad, Prof Maria Eriksdotter, Prof Johan Sandin, Martin Jönsson., 2020 April 2-5; AAT-ADPD.

Stimulating Neurotrophin Receptors in the Treatment of Neurodegenerative Disorders
Nordvall G & Forsell P. Annual Reports in Medicinal Chemistry, 2014.

The Use of TrkA-PathHunter Assay in High-Throughput Screening to Identify Compounds That Affect Nerve Growth Factor Signaling
Forsell P, Almqvist H, Hillertz P, Akerud T, Otrocka M, Eisele L, Sun K, Andersson H, Trivedi S, Wollberg AR, Dekker N, Rottici D & Sandberg K. J. Biomol. Screen., 2013 Jul.

Cholinesterase inhibitors improve both memory and complex learning in aged beagle dogs
Araujo JA, Greig NH, Ingram DK, Sandin J, de Rivera C & Milgram NW. J. Alzheimers Dis., 2011.

Alzstatin

Gamma-secretase modulators: a promising route for the treatment of Alzheimer’s disease
Gunnar Nordvall1,2* Johan Lundkvist1,2,3 Johan Sandin1,2
1AlzeCure Pharma AB, Huddinge, Sweden, 2Department of Neurobiology, Care Sciences, and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden, 3Sinfonia Biotherapeutics AB, Huddinge, Sweden

In vitro and in vivo profile of AC-0027875 (Alzstatin ACD680), a novel gamma-secretase modulator for the prevention and treatment of Alzheimer’s disease
Authors : Märta Dahlström, Lotta Agholme, Maria Backlund, Veronica Lidell, Azita Rasti, Pontus Forsell, Sanja Juric, Magnus M. Halldin, Johan Sandin, Johan Lundkvist, Henrik Zetterberg, Gunnar Nordvall.
AD/PD 2023, March 28 – April 1, 2023.

AC-0027875, a novel gamma-secretase modulator
Authors : Johan Sandin1, Märta Dahlström1, Veronica Lidell1, Azita Rasti1, Pontus Forsell1, Sanja Juric1, Magnus Halldin1, Maria Backlund1, Gunnar Nordvall1
1AlzeCure Pharma AB- Huddinge (Sweden) CTAD 29 nov–2 dec 2022.

γ-Secretase modulators show selectivity for γ-secretase–mediated amyloid precursor protein intramembrane processing Tobias A. Weber, Johan Lundkvist, Johanna Wanngren, Hlin Kvartsberg, ShaoBo Jin, Pia Larssen, Dan Wu, Daniel V. Oliveira, Karolina Minta, Gunnar Brinkmalm, Henrik Zetterberg, Kaj Blennow, Gunnar Nordvall, Bengt Winblad, Erik Portelius, Helena Karlström., Journal of Cellular and Molecular Medicine,  December 20, 2021.

Gamma-secretase modulators show selectivity for gamma-secretase mediated Ab production Lundkvist, J., Weber, TA., Wanngren, J., Kvartsberg, H., Larssen, P., Wu, D., Oliviera, DW., Sandin, J, Zetterberg, H., Blennow, K., Nordvall, G., Winblad, B., Portelius E. and Karlström H., CTAD 2020, CTAD 2020, Nov 4-7.

γ-Secretase: An Unusual Enzyme with Many Possible Disease Targets, Including Alzheimer’s Disease
Lundkvist J. Lendahl U.
(2011), Book chapter 12 in Aspartic Acid Proteases as Therapeutic Targets: 45 (Methods and Principles in Medicinal Chemistry) eds R. Mannhold, H. Kubinyi, G. Folkers and A.K. Ghosh.

Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production
Wanngren J, Ottervald J, Parpal S, Portelius E, Strömberg K, Borgegård T, Klintenberg R, Juréus A, Blomqvist J, Blennow K, Zetterberg H, Lundkvist J, Rosqvist S, Karlström H. J. Biol. Chem., 2012 Sep.

Characterization of intermediate steps in Abeta production under near-native conditions
Olsson F, Schmidt S, Althoff V, Munter M, Jin S, Rosqvist S, Lendahl U, Multhaup G & Lundkvist J. The Journal of Biological Chemistry, 2014.

First and second generation gamma-secretase modulators (GSMs) modulate Abeta production through different mechanisms.
Borgegard T, Jureus A, Olsson F, Rosqvist S, Sabirsh A, Rotticci D, Paulsen K, Klintenberg R, Yan H, Waldman M, Stromberg K, Nord J, Johansson J, Regner A, Parpal S, Malinowsky D, Radesater AC, Li T, Singh R, Eriksson H, Lundkvist J. J. Biol. Chem., 2012 Apr.

Has inhibition of Aβ production adequately been tested as therapeutic approach in mild AD? A model-based meta-analysis of γ-secretase inhibitor data
Niva C, Parkinson J, Olsson F, van Schaick E, Lundkvist J, Visser SA. Eur. J. Clin. Pharmacol., 2013 Jun.

Alzheimer’s disease: Presenilin 2-sparing γ-secretase inhibition is a tolerable Abeta peptide lowering strategy
Borgegård T, Gustavsson S, Nilsson C, Parpal S, Klintenberg R, Berg A-L, Rosqvist S, Serneels L, Svensson S, Olsson F, Jin S, Yan H, Johanna Wanngren J, Jureus A, Ridderstad-Wollberg A, Wollberg P, Stockling K, Karlström H, Malmberg Å, Lund J, Arvidsson PI, De Strooper B, Lendahl U & Lundkvist J. J. Neurosc., 2012 Nov.

Decreased axonal transport rates in the TG2576 APP transgenic mouse: improvement with the gamma-secretase inhibitor MRK-560 as detected by manganese-enhanced MRI
Wang FH, Appelkvist P, Klason T, Gissberg O, Bogstedt A, Eliason K, Martinsson S, Briem S, Andersson A, Visser SAG, Ivarsson M, Lindberg M, Agerman K & Sandin J. Eur. J. Neurosci., 2012.

Sulfonimidamides as Sulfonamides Bioisosteres: Rational Evaluation through Synthetic, in Vitro, and in Vivo Studies with γ-Secretase Inhibitors
Sehgelmeble F, Janson J, Ray C, Rosqvist S, Gustavsson S, Nilsson LI, Minidis A, Holenz J, Rotticci D, Lundkvist J & Arvidsson PI. ChemMedChem., 2012 Mar.

Changed membrane integration and catalytic site conformation are two mechanisms behind the increased Aβ42/Aβ40 ratio by presenilin 1 familial Alzheimer-linked mutations
Wanngren J, Lara P, Ojemalm K, Maioli S, Moradi N, Chen L, Tjernberg LO, Lundkvist J, Nilsson I & Karlström H. FEBS Open Bio., 2014 Apr.

In vivo analysis using a presenilin1-specific inhibitor: presenlin1-containing γ-secretase complexes mediate the majority of CNS Aβ production in the mouse
Borgegård T, Minidis A, Jureus A, Malmborg J, Rosqvist S, Gruber S,Almqvist H, Yan H, Bogstedt A, Olsson F, Dahlström J, Ray C, Närhi K, Malinowsky D, Hagström E, Jin S, Malmberg Å, Lendahl U and Lundkvist J. Alzheimer’s Disease Research Journal. 2011.

Painless

AlzeCure ACD440 TRPV1 antagonist_ Ph 2 data, EFIC 2023 Adriana Miclescu2, MD, PhD, M. Halldin1, MSc Pharm, PhD, Karin Ellström3, MSc Pharm, Rolf Karlsten2, MD, PhD, Märta Segerdahl1,4, MD, PhD, Assoc Prof.

Developing a Nobel Prize winning target in pain.  Segerdahl M, Jönsson M, Sandin J. MedNous 2021.

Negative allosteric modulators of TrkA for the treatment of pain  Nordvall, G., Dahlström, M., Parrado, C., Backlund, M., Lidell, V., Halldin, M., Sandin, J. and Forsell, P., IASP 2021, June 27-July 1.

ACD440 – A Novel TRPV1 Antagonist for the Topical Treatment of Pain  Schaffler, K., Popescu, T., Hellgren, M., Schipper, N., Gripenhall, A., Sandin, J., Forsell, P., Segerdahl, M. and Rother, M., IASP 2021, June 27-July 1.

Drug discovery & development

Neuronal cell-based high-throughput screen for enhancers of mitochondrial function reveals luteolin as a modulator of mitochondria-endoplasmic reticulum coupling
Naia L, Pinho CM, Dentoni G, Liu J, Leal NS, Ferreira DMS, Schreiner B, Filadi R, Fão L, Connolly NMC, Forsell P, Nordvall G, Shimozawa M, Greotti E, Basso E, Theurey P, Gioran A, Joselin A, Arsenian-Henriksson M, Nilsson P, Rego AC, Ruas JL, Park D, Bano D, Pizzo P, Prehn JHM, Ankarcrona M. BMC Biol. 2021 Mar.

The battle of Alzheimer’s Disease – the beginning of the future Unleashing the potential of academic discoveries
Lundkvist J, Halldin MM, Sandin J, Nordvall G, Forsell P, Svensson S, Jansson L, Johansson G, Winblad B & Ekstrand J. Frontiers in Pharmacology, 2014.

Revisiting the peripheral sink hypothesis: Inhibiting BACE1 activity in the periphery does not alter β-amyloid levels in the CNS
Georgievska B, Gustavsson S, Lundkvist J, Neelissen J, Eketjäll S, Ramberg V, Bueters T, Agerman K, Juréus A, Svensson S, Berg S, Fälting J & Lendahl U. J. Neurochem., 2015.

Creation of Novel Cores for β-Secretase (BACE-1) Inhibitors: A Multi-Parameter Lead Generation Strategy
Viklund J, Kolmodin K, Nordvall G, Swahn B-M, Svensson M, Gravenfors Y & Rahm F. ACS Medicinal Chemistry Letters, 2014.

BACE1 Inhibition Induces a Specific Cerebrospinal Fluid β-Amyloid Pattern That Identifies Drug Effects in the Central Nervous System
Mattsson N, Rajendran L, Zetterberg H, Gustavsson M, Andreasson U, Olsson M, Brinkmalm G, Lundkvist J, Jacobson LH, Perrot L, Neumann U, Borghys H, Mercken M, Dhuyvetter D, Jeppsson F, Blennow K & Portelius E. Plos One, 2012.

Endogenous APP accumulates in synapses after BACE1 inhibition
Nigam SM, Xu S, Ackermann F, Gregory JA, Lundkvist J, Lendahl U & Brodin L. Neurosci. Res., 2016 Aug.

Pragmatic Approaches to Determine the Exposures of Drug Metabolites in Preclinical and Clinical Subjects in the MIST Evaluation
Haglund J, Halldin MM, Brunnström Å, Eklund G, Kautiainen A, Sandholm A & Iverson SL. Chem. Res. Toxicol., 2014.

Assessment of free drug concentration in cyclodextrin formulations is essential to determine drug potency in functional in vitro assays
Sjögren E, Andersson S, Sundgren-Andersson AK, Halldin MM & Stålberg O. J. Pharm. Sci., 2016;105:2913-20.
Preclinical characterization of three transient receptor potential vanilloid receptor 1 antagonists for early use in human intradermal microdose analgesic studies
Sjögren E, Halldin MM, Stålberg O & Sundgren-Andersson AK. European Journal of Pain, 2018.

Clinical testing of three novel transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonists in a pharmacodynamic intradermal capsaicin model
Sjögren E, Kullenberg T, Jonzon B, Segerdahl M, Stålberg O, Halldin MM & Sundgren-Andersson AK. European Journal of Pain, 2018.

AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans
Georgievska B, Sandin J, Doherty J, Mörtberg A, Neelissen J, Andersson A, Gruber S, Nilsson Y, Schött P, Arvidsson PI, Hellberg S, Osswald G, Berg S, Fälting J & Bhat RV. J. Neurochem., 2013 May.