Ladislav Mrzljak

Study protocol for the iMarkHD study in individuals with Huntington's disease

Daniel J. van Wamelen, Naomi H. Martin, Orsolya Makos, James Badenoch et autres

Background: Huntington's disease (HD) is still often defined by the onset of motor symptoms, inversely associated with the size of the CAG repeat expansion in the huntingtin gene. Although the cause of HD is known, much remains unknown about mechanisms underlying clinical …

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Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington’s disease

Tamara Vasilkovska, Somaie Salajeghe, Verdi Vanreusel, Johan Van Audekerke et autres

BACKGROUND: Huntington's disease (HD) is marked by a CAG-repeat expansion in the huntingtin gene that causes neuronal dysfunction and loss, affecting mainly the striatum and the cortex. Alterations in the neurovascular coupling system have been shown to lead to dysregulated energy supply …

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Development of a ligand for in vivo imaging of mutant huntingtin in Huntington’s disease

Daniele Bertoglio, Jonathan Bard, Manuela Heßmann, Longbin Liu et autres

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion in the huntingtin ( HTT ) gene that encodes the pathologic mutant HTT (mHTT) protein with an expanded polyglutamine (polyQ) tract. Whereas several therapeutic programs targeting mHTT …

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Longitudinal preclinical evaluation of the novel radioligand [11C]CHDI-626 for PET imaging of mutant huntingtin aggregates in Huntington’s disease

Daniele Bertoglio, Jeroen A.J. Verhaeghe, Alan Miranda, Leonie Wyffels et autres

Abstract Purpose As several therapies aimed at lowering mutant huntingtin (mHTT) brain levels in Huntington’s disease (HD) are currently being investigated, noninvasive positron emission tomography (PET) imaging of mHTT could be utilized to directly evaluate therapeutic efficacy and monitor disease progression. Here …

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Synaptic Vesicle Glycoprotein 2A Is Affected in the Central Nervous System of Mice with Huntington Disease and in the Brain of a Human with Huntington Disease Postmortem

Daniele Bertoglio, Jeroen A.J. Verhaeghe, Leonie Wyffels, Alan Miranda et autres

Synaptic dysfunction is a primary mechanism underlying Huntington’s Disease (HD) progression. This study investigated changes in synaptic vesicle glycoprotein 2A (SV2A) density by means of 11C-UCB-J microPET imaging in the central nervous system (CNS) of HD mice. METHODS: Dynamic 11C-UCB-J microPET imaging …

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Longitudinal Preclinical Evaluation of the Novel Radioligand [11C]CHDI-626 for PET Imaging of Mutant Huntingtin Aggregates in Huntington’s Disease

Daniele Bertoglio, Jeroen A.J. Verhaeghe, Alan Miranda, Leonie Wyffels et autres

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[11C]CHDI-626, a PET Tracer Candidate for Imaging Mutant Huntingtin Aggregates with Reduced Binding to AD Pathological Proteins

Longbin Liu, Peter Johnson, Michael E. Prime, Vinod K. Khetarpal et autres

The expanded polyglutamine-containing mutant huntingtin (mHTT) protein is implicated in neuronal degeneration of medium spiny neurons in Huntington’s disease (HD) for which multiple therapeutic approaches are currently being evaluated to eliminate or reduce mHTT. Development of effective and orthogonal biomarkers will ensure …

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A novel imaging ligand as a biomarker for mutant huntingtin-lowering in Huntington’s disease

Daniele Bertoglio, Jonathan Bard, Manuela Heßmann, Longbin Liu et autres

Abstract Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion in the huntingtin ( HTT ) gene that encodes the pathologic mutant HTT (mHTT) protein with an expanded polyglutamine (PolyQ) tract. While several therapeutic programs targeting …

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Imaging Mutant Huntingtin Aggregates: Development of a Potential PET Ligand

Longbin Liu, Michael E. Prime, Matt R. Lee, Vinod K. Khetarpal et autres

Abstract Mutant huntingtin (mHTT) protein carrying the elongated N-terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates characteristic of Huntington’s disease (HD) pathology. A high-affinity ligand specific for mHTT aggregates could serve as a positron emission tomography (PET) imaging biomarker for HD …

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PET Molecular Imaging of Phosphodiesterase 10A: An Early Biomarker of Huntington's Disease Progression

Patrik Fazio, Cheryl J. Fitzer‐Attas, Ladislav Mrzljak, Juliana Bronzova et autres

Abstract Background Changes in phosphodiesterase 10A enzyme levels may be a suitable biomarker of disease progression in Huntington's disease. Objectives To evaluate phosphodiesterase 10A PET imaging as a biomarker of HD progression using the radioligand, [18F]MNI‐659. Methods The cross‐sectional study (NCT02061722) included …

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Elevated Type 1 Metabotropic Glutamate Receptor Availability in a Mouse Model of Huntington’s Disease: a Longitudinal PET Study

Daniele Bertoglio, Jeroen A.J. Verhaeghe, Špela Korat, Alan Miranda et autres

Abstract Impairment of group I metabotropic glutamate receptors (mGluRs) results in altered glutamate signalling, which is associated with several neurological disorders including Huntington’s Disease (HD), an autosomal neurodegenerative disease. In this study, we assessed in vivo pathological changes in mGluR1 availability in …

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In vitro and In vivo Assessment of Suitable Reference Region and Kinetic Modelling for the mGluR1 Radioligand [11C]ITDM in Mice

Daniele Bertoglio, Jeroen A.J. Verhaeghe, Špela Korat, Alan Miranda et autres

Abstract Purpose This study aimed at investigating binding specificity, suitability of reference region-based kinetic modelling, and pharmacokinetics of the metabotropic glutamate receptor 1 (mGluR1) radioligand [11C]ITDM in mice. Procedures We performedin vivoblocking as well as displacement of [11C]ITDM during positron emission tomography …

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