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Article

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

1
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK
2
California Movement Disorders Center, Los Gatos, CA 95032, USA
3
Retrotope, Los Altos, CA 94022, USA
4
Laboratory of Regenerative Medicine–Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, via F. Sforza 35, 20122 Milano, Italy
*
Authors to whom correspondence should be addressed.
Academic Editors: Tawfeeq Shekh-Ahmad and Ron Kohen
Antioxidants 2021, 10(7), 1021; https://doi.org/10.3390/antiox10071021
Received: 27 May 2021 / Revised: 18 June 2021 / Accepted: 22 June 2021 / Published: 25 June 2021
(This article belongs to the Special Issue Reactive Oxygen Species in Central Nervous System Disorders)
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. View Full-Text
Keywords: PSP; lipid peroxidation; RT001; PUFA; mesenchymal stem cells; deuteration PSP; lipid peroxidation; RT001; PUFA; mesenchymal stem cells; deuteration
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MDPI and ACS Style

Angelova, P.R.; Andruska, K.M.; Midei, M.G.; Barilani, M.; Atwal, P.; Tucher, O.; Milner, P.; Heerinckx, F.; Shchepinov, M.S. RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations. Antioxidants 2021, 10, 1021. https://doi.org/10.3390/antiox10071021

AMA Style

Angelova PR, Andruska KM, Midei MG, Barilani M, Atwal P, Tucher O, Milner P, Heerinckx F, Shchepinov MS. RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations. Antioxidants. 2021; 10(7):1021. https://doi.org/10.3390/antiox10071021

Chicago/Turabian Style

Angelova, Plamena R., Kristin M. Andruska, Mark G. Midei, Mario Barilani, Paldeep Atwal, Oliver Tucher, Peter Milner, Frederic Heerinckx, and Mikhail S. Shchepinov. 2021. "RT001 in Progressive Supranuclear Palsy—Clinical and In-Vitro Observations" Antioxidants 10, no. 7: 1021. https://doi.org/10.3390/antiox10071021

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