Hassan, Yara Refaat Amin Ibrahim;
(2022)
Investigations of Tominersen (RG6042) as a potential therapeutic for Huntington’s disease and studying the safety and tolerability of the lumbar puncture procedure in patients with Huntington’s disease.
Doctoral thesis (Ph.D), UCL (University College London).
Abstract
Huntington’s disease (HD) is a progressive neurodegenerative disease, for which to date, no single therapy has proven effective in slowing the disease progression over time. However, there is a tremendous effort by scientists worldwide to investigate and develop effective disease-modifying therapy. Tominersen (RG6042) program by F. Hoffmann–La Roche therapeutics is one of the global clinical trials that is based on developing Antisense Oligonucleotide (ASO) therapy to lower the mutant Huntington protein which when accumulates leads to the characteristic neuronal cell toxicity and degeneration observed in the brains of patients with Huntington’s disease. An essential part of this program was the HD Natural History Study (HD NHS) (NCT03664804), to investigate the natural progression of the disease and to act as a comparator arm to the open-label extension phase (OLE) of Roche Tominersen program phase I/IIa study (NCT03342053). This thesis documents the recruitment and analysis of the HD Natural History Study at the UCL site, and will present the changes in the clinical and cognitive endpoints over the course of the study (approximately 15 months) in patients with early HD recruited at the UCL site. Another important part of the Roche Tominersen program was phase III study (also known as Generation HD1 study) (NCT03761849) to assess the safety and efficacy of tominersen. In this thesis, I document the recruitment and analysis of the GenerationHD1 Study at the UCL site, and I will present deep clinical phenotypic data of the two Huntington's disease participants enrolled at the UCL site. In this thesis, I will also discuss the results of the phase III study which was presented and shared by Roche. I will discuss my views on why tominersen failed to prove efficacy. Given that lumbar puncture (LP) was an essential procedure in my work in the above two studies, to administer tominersen drug intrathecally and to collect cerebrospinal fluid (CSF), I will present in this thesis my work to study the safety and the tolerability of the LP procedure in patients with Huntington’s disease.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigations of Tominersen (RG6042) as a potential therapeutic for Huntington’s disease and studying the safety and tolerability of the lumbar puncture procedure in patients with Huntington’s disease |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10160603 |
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