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Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy

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M. Garcia-Montojo, S. Fathi, G. Norato, B. R. Smith, D. B. Rowe, M. C. Kiernan, S. Vucic, S. Mathers, R. P.A. van Eijk, U. Santamaria, M. L. Rogers, A. Malaspina, V. Lombardi, P. R. Mehta, H. J. Westeneng, L. H. van den Berg, A. Al-Chalabi, J. Gold, A. Nath

Original languageEnglish
Article number117358
JournalJournal of the Neurological Sciences
Accepted/In press2021
Published15 Apr 2021

Bibliographical note

Funding Information: We would like to thank all the patients who participated in the study. This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at NIH (NS 003130) and the ALS Association (20-SI-559). This is in part an EU Joint Programme - Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND - (United Kingdom, Medical Research Council (MR/L501529/1; MR/R024804/1)) and through the Motor Neuron Disease Association. This study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The Lighthouse trial in Australia was supported by FightMND and the MND Research Institute of Australia. Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Reactivation of Human Endogenous Retrovirus K (HERV-K), subtype HML-2, has been associated with pathophysiology of amyotrophic lateral sclerosis (ALS). We aimed to assess the efficacy of antiretroviral therapy in inhibiting HML-2 in patients with ALS and a possible association between the change in HML-2 levels and clinical outcomes. We studied the effect of 24-weeks antiretroviral combination therapy with abacavir, lamivudine, and dolutegravir on HML-2 levels in 29 ALS patients. HML-2 levels decreased progressively over 24 weeks (P = 0.001) and rebounded within a week of stopping medications (P = 0.02). The majority of participants (82%), defined as “responders”, experienced a decrease in HML-2 at week 24 of treatment compared to the pre-treatment levels. Differences in the evolution of some of the clinical outcomes could be seen between responders and non-responders: FVC decreased 23.69% (SE = 11.34) in non-responders and 12.71% (SE = 8.28) in responders. NPI score decreased 91.95% (SE = 6.32) in non-responders and 53.05% (SE = 10.06) in responders (P = 0.01). Thus, participants with a virological response to treatment showed a trend for slower progression of the illness. These findings further support the possible involvement of HML-2 in the clinical course of the disease.

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