Supplement (online only): Proceedings of the 14th Göttingen Meeting of the German Neuroscience Society 2021
Year: 2021
Type: article
Abstract: There are no effective disease-modifying therapies for neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS) or Huntington's disease (HD).Huntington's disease (HD) is a devastating autosomal dominantly inherited neurodegenerative disease and the genetic predictability of HD provides an opportunity for early therapeutic intervention many years before overt symptom onset and at a time when reversal or prevention of neural dysfunction may still be possible.As HD is monogenetic, fully penetrant, and characterised by a long premanifest phase, it is emerging as a potential model for studying therapeutic intervention in other neurodegenerative conditions such as Alzheimer's or Parkinson's disease where no preclinical diagnostic tests exist.In addition, HD manifests with a broad range of clinical symptoms and signs, many of them common to these other diseases, and involves widespread pathology throughout most of the brain involving similar protein misfolding.Understanding of HD pathogenesis is evolving, and I will present an overview of important approaches in development for targeting mutant HTT DNA and RNA, the cause of HD pathogenesis (Tabrizi Neuron 2019), and in particular I will present our recent successful phase 1b/2a clinical trial testing the effects of antisense oligonucleotide therapy (ASO) with Tominersen (formerly known as IONIS HTT Rx) in patients with early Huntington's Disease and present the results of the first successful HTT-lowering drug trial (Tabrizi et al New England Journal of Medicine 2019).This study is the first to demonstrate antisense-mediated protein suppression in patients with a neurodegenerative disease.While this ASO has potential for HD, our findings have broader implications.These data suggest that antisense technology has the potential to provide disease-modifying benefits in other neurodegenerative diseases associated with aberrant production of proteins, including ALS, Alzheimer's disease and many other diseases that currently lack adequate treatments (Tabrizi Science 2020).In my talk I will review ASO approaches in development for CNS diseases.
Source: e-Neuroforum
DOI: 10.1515/nf-2021-2003
Authors: Steponaitis, Giedrius, Kučinskas, Vytautas, Saudargienė, Aušra, Tamašauskas, Arimantas
Institutions: University of Copenhagen, University of Freiburg, King's College London, Washington University in St. Louis, University of Würzburg, John Radcliffe Hospital, University of Oxford, UCL Queen Square Institute of Neurology, University College London, University of Tübingen, Ludwig-Maximilians-Universität München
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Awards: G1129793973, G1136968976, G1163571418, G122987265, G1473407238, G1480874411, G1543164668, G1595975132, G2104224606, G2269957163, Die Funktion und Verbindungen der NeocortikalenSchicht 7 und weitreichenden Eingaben zu somatosensorichen Kortex., G2707994935, G2760294848, G3160699921, G3315589503, G3333728379, SFB 1315: Mechanismen und Störungen der Gedächtniskonsolidierung: Von Synapsen zur Systemebene, G3936970252, Human Brain Project Specific Grant Agreement 1, G4223297884, G4236712713, G434337789, Prospektive Kodierung bei kortikalen Pyramidenzellen, G4937468798, G5045127959, G5193558347, G5216280409, Cognitive Interaction in Motion, Human Brain Project Specific Grant Agreement 2, G6542926802, G6607577419, G7114870094, G7420846792, G7882196468, Hierarchische Koordination komplexer Bewegungen, Dendritische Dynamik und die Wahrnehmungsschwelle, G8580271377, G8683586189, Human Brain Project Specific Grant Agreement 3
OpenAlex ID: W4285508578