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

Garcia-Montojo, M; Fathi, S; Smith, BR; Rowe, DB; Kiernan, MC; Vucic, S; Mathers, S; ... Nath, A; + view all (2021) Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy. JOURNAL OF THE NEUROLOGICAL SCIENCE Journal of the Neurological Sciences S , 423 , Article 117358. 10.1016/j.jns.2021.117358. Green open access

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Abstract

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.

Type: Article
Title: Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jns.2021.117358
Publisher version: http://dx.doi.org/10.1016/j.jns.2021.117358
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Amyotrophic lateral sclerosis, ALS, HERV-K, HML-2, Antiretroviral
UCL classification: UCL
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 > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10190008
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