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RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations

Progressive supranuclear palsy (PSP) is a progressive movement disorder associated with lipid peroxidation and intracerebral accumulation of tau. RT001 is a deuterium reinforced isotopologue of linoleic acid that prevents lipid peroxidation (LPO) through the kinetic isotope effect. The effects of RT...

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Autores principales: Angelova, Plamena R., Andruska, Kristin M., Midei, Mark G., Barilani, Mario, Atwal, Paldeep, Tucher, Oliver, Milner, Peter, Heerinckx, Frederic, Shchepinov, Mikhail S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300819/
https://www.ncbi.nlm.nih.gov/pubmed/34202031
http://dx.doi.org/10.3390/antiox10071021
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author Angelova, Plamena R.
Andruska, Kristin M.
Midei, Mark G.
Barilani, Mario
Atwal, Paldeep
Tucher, Oliver
Milner, Peter
Heerinckx, Frederic
Shchepinov, Mikhail S.
author_facet Angelova, Plamena R.
Andruska, Kristin M.
Midei, Mark G.
Barilani, Mario
Atwal, Paldeep
Tucher, Oliver
Milner, Peter
Heerinckx, Frederic
Shchepinov, Mikhail S.
author_sort Angelova, Plamena R.
collection PubMed
description Progressive supranuclear palsy (PSP) is a progressive movement disorder associated with lipid peroxidation and intracerebral accumulation of tau. RT001 is a deuterium reinforced isotopologue of linoleic acid that prevents lipid peroxidation (LPO) through the kinetic isotope effect. The effects of RT001 pre-treatment on various oxidative and bioenergetic parameters were evaluated in mesenchymal stem cells (MSC) derived from patients with PSP compared to controls. In parallel, 3 patients with PSP were treated with RT001 and followed clinically. MSCs derived from PSP patients had a significantly higher rate of LPO (161.8 ± 8.2% of control; p < 0.001). A 72-h incubation with RT001 restored the PSP MSCs to normal levels. Mitochondrial reactive oxygen species (ROS) overproduction in PSP-MSCs significantly decreased the level of GSH compared to control MSCs (to 56% and 47% of control; p < 0.05). Incubation with RT001 significantly increased level of GSH in PSP MSCs. The level of mitochondrial DNA in the cells was significantly lower in PSP-MSCs (67.5%), compared to control MSCs. Changes in mitochondrial membrane potential, size, and shape were also observed. Three subjects with possible or probable PSP were treated with RT001 for a mean duration of 26 months. The slope of the PSPRS changed from the historical decline of 0.91 points/month to a mean decline of 0.16 points/month (+/−0.23 SEM). The UPDRS slope changed from an expected increase of 0.95 points/month to an average increase in score of 0.28 points/month (+/−0.41 SEM). MSCs derived from patients with PSP have elevated basal levels of LPO, ROS, and mitochondrial dysfunction. These findings are reversed after incubation with RT001. In PSP patients, the progression of disease may be reduced by treatment with RT001.
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spelling pubmed-83008192021-07-24 RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations Angelova, Plamena R. Andruska, Kristin M. Midei, Mark G. Barilani, Mario Atwal, Paldeep Tucher, Oliver Milner, Peter Heerinckx, Frederic Shchepinov, Mikhail S. Antioxidants (Basel) Article Progressive supranuclear palsy (PSP) is a progressive movement disorder associated with lipid peroxidation and intracerebral accumulation of tau. RT001 is a deuterium reinforced isotopologue of linoleic acid that prevents lipid peroxidation (LPO) through the kinetic isotope effect. The effects of RT001 pre-treatment on various oxidative and bioenergetic parameters were evaluated in mesenchymal stem cells (MSC) derived from patients with PSP compared to controls. In parallel, 3 patients with PSP were treated with RT001 and followed clinically. MSCs derived from PSP patients had a significantly higher rate of LPO (161.8 ± 8.2% of control; p < 0.001). A 72-h incubation with RT001 restored the PSP MSCs to normal levels. Mitochondrial reactive oxygen species (ROS) overproduction in PSP-MSCs significantly decreased the level of GSH compared to control MSCs (to 56% and 47% of control; p < 0.05). Incubation with RT001 significantly increased level of GSH in PSP MSCs. The level of mitochondrial DNA in the cells was significantly lower in PSP-MSCs (67.5%), compared to control MSCs. Changes in mitochondrial membrane potential, size, and shape were also observed. Three subjects with possible or probable PSP were treated with RT001 for a mean duration of 26 months. The slope of the PSPRS changed from the historical decline of 0.91 points/month to a mean decline of 0.16 points/month (+/−0.23 SEM). The UPDRS slope changed from an expected increase of 0.95 points/month to an average increase in score of 0.28 points/month (+/−0.41 SEM). MSCs derived from patients with PSP have elevated basal levels of LPO, ROS, and mitochondrial dysfunction. These findings are reversed after incubation with RT001. In PSP patients, the progression of disease may be reduced by treatment with RT001. MDPI 2021-06-25 /pmc/articles/PMC8300819/ /pubmed/34202031 http://dx.doi.org/10.3390/antiox10071021 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Angelova, Plamena R.
Andruska, Kristin M.
Midei, Mark G.
Barilani, Mario
Atwal, Paldeep
Tucher, Oliver
Milner, Peter
Heerinckx, Frederic
Shchepinov, Mikhail S.
RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations
title RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations
title_full RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations
title_fullStr RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations
title_full_unstemmed RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations
title_short RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations
title_sort rt001 in progressive supranuclear palsy—clinical and in-vitro observations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300819/
https://www.ncbi.nlm.nih.gov/pubmed/34202031
http://dx.doi.org/10.3390/antiox10071021
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