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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number117358
Pages (from-to)1-6
Number of pages6
JournalJournal of the Neurological Sciences
Volume423
DOIs
Publication statusPublished - 15 Apr 2021

Keywords

  • ALS
  • Amyotrophic lateral sclerosis
  • Antiretroviral
  • HERV-K
  • HML-2

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