Manfred Windisch

Randomized phase 2a trial assessing a novel septin molecular glue in Alzheimer's disease

Mieke Nuytten, Marieke Voets, Eveline Debroux, Katrien Princen et autres

INTRODUCTION: Pharmacological restoration of septin filament integrity has the potential to provide symptomatic benefit and disease modification in Alzheimer's disease (AD). METHODS: REM127, a septin modulator, was assessed in mild-to-moderate AD (EudraCT: 2022-000080-43) in a phase 2a trial (n = 14). PRIMARY …

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p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial

Hayley R. C. Shanks, Kewei Chen, Eric M. Reiman, Kaj Blennow et autres

Abstract p75 neurotrophin receptor (p75 NTR ) signaling pathways substantially overlap with degenerative networks active in Alzheimer disease (AD). Modulation of p75 NTR with the first-in-class small molecule LM11A-31 mitigates amyloid-induced and pathological tau-induced synaptic loss in preclinical models. Here we conducted …

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Wie werden langwirksame Wachstumshormonpräparate in Österreich von Ärzt*innen und Patienteneltern wahrgenommen?

Jelena Belic, Theresa Zekoll, Stefan Riedl, Manfred Windisch

Zusammenfassung Rekombinantes humanes Wachstumshormon muss aufgrund seiner kurzen Halbwertszeit täglich injiziert werden. Dieses Behandlungsregime kann für Patient*innen und ihre Familien eine ganz erhebliche Belastung darstellen. Langwirksame Wachstumshormone (LAGH) sind eine neuartige Behandlungsoption, die durch eine 1‑mal wöchentliche Verabreichung eine reduzierte Injektionsfrequenz ermöglicht. …

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Age‐dependent effects of the p75 neurotrophin receptor modulator LM11A‐31 on Alzheimer’s disease biomarkers in a 26‐week safety and exploratory endpoint trial

Hayley R. C. Shanks, Anne Börjesson‐Hanson, Manfred Windisch, Stephen M. Massa et autres

Abstract Background The p75 neurotrophin receptor (p75NTR) modulates pro‐ and anti‐apoptotic pathways as well as neurite and neuritic spine integrity. This receptor is expressed in cells vulnerable to aging and disease, including basal forebrain cholinergic neurons and hippocampal pyramidal neurons. It is …

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Phase 1 Trials in Alzheimer’s Disease Drug Development

Manfred Windisch

Phase 1 clinical trials are the entrance to the further clinical development of new compounds. The chapter describes the regulatory background and highlights most important issues about selection of the maximum recommended starting dose, dose escalation steps, and definition of maximum tolerated …

Development of an orally bioavailable stress kinase inhibitor with brain exposure that targets the neuroinflammation‐synaptic dysfunction pathophysiology axis

Daniel Martin Watterson, Ottavio Arancio, Manfred Windisch, Jeffrey C. Pelletier et autres

Abstract Background An ambitious primary goal of NAPA is to identify disease modifying interventions, a goal complicated by the nearly complete failure of all clinical trials. However, a common yet neglected target is the pathophysiology progression theme of synaptic dysfunction associated with …

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Clinical phase I data of the first orally available anti‐aβ‐prionic drug PRI‐002 that reverses behavioral and cognitive deficits, and decelerates neurodegeneration in AD animal models

Dieter Willbold, Janine Kutzsche, Antje Willuweit, Manfred Windisch et autres

Abstract Background More and more data suggest that the toxic protein assemblies of Aβ and TAU behave prion like. The drug candidate PRI‐002 has been developed to directly disassemble and destroy toxic Aβ oligomer prions. The anti‐prionic compound PRI‐002 (alias “RD2”) is …

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Safety and pharmacokinetics of the orally available antiprionic compound PRI‐002: A single and multiple ascending dose phase I study

Janine Kutzsche, Dagmar Jürgens, Antje Willuweit, Knut Adermann et autres

INTRODUCTION: PRI-002 is an orally available anti-amyloid beta (Aβ) prionic compound developed for direct disassembly of toxic Aβ oligomers relevant to Alzheimer's disease. METHODS: Two placebo-controlled clinical phase I trials with oral dosing of PRI-002 were conducted in healthy young subjects: A …

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Translational animal models for Alzheimer's disease: An Alzheimer's Association Business Consortium Think Tank

Michael Peter Vitek, Joseph A. Araujo, Michael Fossel, Barry Greenberg et autres

Over 5 million Americans and 50 million individuals worldwide are living with Alzheimer's disease (AD). The progressive dementia associated with AD currently has no cure. Although clinical trials in patients are ultimately required to find safe and effective drugs, animal models of …

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Diffusion kurtosis imaging detects brain microstructural alterations in three mouse models of Parkinson’s disease

Jana Rudá, Eva Dražanová, Alžběta Šejnoha Minsterová, Anas Arab et autres

The aim of this research is to test the ability of diffusion kurtosis imaging (DKI) to detect Parkinson´s disease-like pathology at an early stage when a neuroprotective treatment may still be effective.

BACE1-cleavage of Sez6 and Sez6L is elevated in Niemann-Pick type C disease mouse brains

Mirsada Čaušević, Kristina Dominko, Martina Malnar, Lea Vidatic et autres

It is intriguing that a rare, inherited lysosomal storage disorder Niemann-Pick type C (NPC) shares similarities with Alzheimer's disease (AD). We have previously reported an enhanced processing of β-amyloid precursor protein (APP) by β-secretase (BACE1), a key enzyme in the pathogenesis of …

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Development of GMP ‐1 a molecular chaperone network modulator protecting mitochondrial function and its assessment in fly and mice models of Alzheimer's disease

Pavel F. Pavlov, Birgit Hutter‐Paier, Daniel Havas, Manfred Windisch et autres

Abstract Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD) and may play an important role in the pathogenesis of disease. It has been shown that amyloid beta peptide (Aβ) and amyloid precursor protein (APP) interact with mitochondria contributing to the …

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