Ett urval av artiklar publicerade av ledningen av AlzeCure Pharma.
NeuroRestore
Further investigation on the immunomodulatory and anti-inflammatory effects of NeuroRestore ACD856, a Trk-PAM in clinical development for the treatment of Alzheimer’s disease
Cristina Parrado-Fernández, Ruchi Gera, Veronica Lidell, Azita Rasti, Sumonto Mitra, Maria Backlund, Gunnar Nordvall, Johan Sandin, Maria Eriksdotter, Pontus Forsell, AD/PD 2025
Preclinical evidence for anti-inflammatory and immunomodulatory effects of NeuroRestore ACD856, a Trk-PAM in clinical development for the treatment of Alzheimer’s disease.
Cristina Parrado-Fernández, Ruchi Gera, Veronica Lidell, Azita Rasti, Sumonto Mitra, Maria Backlund, Gunnar Nordvall, Martin Jönsson, Johan Sandin, Maria Eriksdotter, Pontus Forsell, CTAD 2024
Positive Allosteric Modulators of Trk Receptors for the Treatment of Alzheimer’s Disease
Pontus Forsell, PhD and Head of Discovery and Research at AlzeCure Pharma. Co-authors are Cristina Parrado Fernández, Boel Nilsson, Johan Sandin, Gunnar Nordvall and Märta Segerdahl. Pharmaceuticals, ;17(8):997, 28 July 2024
ACD856 is a biased positive allosteric modulator of Trk-receptors – Enhances neurite outgrowth but do not affect pain signaling
Pontus Forsell, Veronica Lidell, Azita Rasti, Gunnar Nordvall och Johan Sandin. AD/PD March 2024.
ACD856, a novel positive allosteric modulator of Trk receptors, single ascending doses in healthy subjects: Safety and pharmacokinetics
Nilsson B, Bylund J, Halldin MM, Rother M, Rein-Hedin E, Önnestam K, Segerdahl M. Eur J Clin Pharmacol. 2024 Feb 14.
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
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
Cristina Parrado-Fernández, Gunnar Nordvall, Sanja Juric, Nather Madjiid, Maria Backlund, Märta Dahlström, Johan Sandin, Pontus Forsell CTAD 29 nov–2 dec 2022.
Quantitative EEG results from a multiple ascending dose study
Martin Jönsson, Kristin Önnestam, Boel Nilsson, Matthias Rother, Erik Rein- Hedin, Peter Anderer, Manuel Kemethofer, Magnus Halldin, Pontus Forsell, Gunnar Nordvall, Johan Sandin, Märta Segerdahl. 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 Dahlström, Johan Sandin, Pontus Forsell.
Neurotrophin targeted therapeutics – a gateway to cognition and more? Dr. Gunnar Nordvall, Head of Chemistry, Dr. Pontus Forsell, Head of Research and Discovery and Dr. Johan Sandin, CSO, Aug 16, 2022.
Results From a Multiple Ascending Dose Study in Healthy Volunteers of ACD856, a Positive Modulator of Neurotrophin Trk-Receptors
Kristin Önnestam MSc, Matthias Rother MD, PhD, Erik Rein-Hedin MD, Johan Bylund PhD, Magnus M Halldin PhD, Boel Nilsson MSc, Pontus Forsell PhD, Gunnar Nordvall PhD, Johan Sandin PhD, Märta Segerdahl MD, PhD. AAIC, July – Aug., 2022
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 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.
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.
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.
Characterization of positive allosteric modulators of TrkB for the treatment of depression; Scientific presentation at ECNP
Sandin, J., Nordvall, G., Madjid, N., Dahlström, M., Parrado, C., Backlund, M., Lidell, V., Halldin, M. and Forsell, P., 2021 October 2-5.
Alzstatin
γ-Secretase modulation inhibits amyloid plaque formation and growth and stimulates plaque regression in amyloid precursor protein/presenilin-1 mice
Gunnar Nordvall, Ping Yan, Lotta Agholme, Johan Lundkvist, Johan Sandin , Henrik Biverstål, Bengt Winblad, Henrik Zetterberg, Rebecka Klintenberg, Mats Ferm, John R. Cirrito, Jin-Moo Lee , JPET, April 2025
Gamma-secretase modulators: a promising route for the treatment of Alzheimer’s disease
Gunnar Nordvall1, Johan Lundkvist1, Johan Sandin
AlzeCure Pharma AB, Huddinge, Sweden, Department of Neurobiology, Care Sciences, and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, 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
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
Johan Sandin, Märta Dahlström, Veronica Lidell, Azita Rasti, Pontus Forsell, Sanja Juric, Magnus Halldin, Maria Backlund, Gunnar Nordvall. 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, 20 December 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
Pharmacological Effects of ACD137, a Small Molecule Negative Allosteric Modulator of TrkA
Forsell, P., Nordvall, G., Backlund, M., Lidell, V., Rasti, A., Parrado-Fernandez, C., Sandin, J. and Segerdahl, M., IASP August 2024, World Congress on Pain, Amsterdam
Topically applied novel TRPV1 receptor antagonist, ACD440 Gel, reduces evoked pain in healthy volunteers, a randomized, double-blind, placebo-controlled, crossover study
M. Segerdahl, M. Rother, M. M. Halldin, T. Popescu, K. Schaffler, EUR. J Pain, June 2024
AlzeCure ACD440 TRPV1 antagonist_ Ph 2 data Adriana Miclescu, MD, PhD, M. Halldin, MSc Pharm, PhD, Karin Ellström, MSc Pharm, Rolf Karlsten, MD, PhD, Märta Segerdahl1, MD, PhD, Assoc Prof., EFIC 2023
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., Scientific presentation at 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., Scientific presentation at IASP, 2021 June 27-July 1.
The use of TrkA-PathHunterTM assay in high throughput screening to identify compounds that intervene with nerve growth factor signaling Pontus Forsell, Helena Almqvist, Magdalena Otrocka, Lina Eisele, Kai Sun, Henrik Andersson, Shephali Trivedi, Niek Dekker and Kristian Sandberg, 2013, Journal of Biomolecular screening, 2013 Jul;18(6):659-569.
Drug discovery & development
Pharmacological Effects of ACD137, a Potent and Selective Negative Allosteric Modulator of TrkA
Pontus Forsell, project leader and Head of Discovery and Research at AlzeCure. The other authors include Gunnar Nordvall, Maria Backlund, Veronica Lidell, Azita Rasti, Cristina Parrado-Fernandez, Johan Sandin and Märta Segerdahl. IASP 2024 World Congress on Pain on August 5-9
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.