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. 2021 Apr 15:423:117358.
doi: 10.1016/j.jns.2021.117358. Epub 2021 Feb 23.

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

M Garcia-Montojo  1 , S Fathi  1 , G Norato  1 , B R Smith  1 , D B Rowe  2 , M C Kiernan  3 , S Vucic  4 , S Mathers  5 , R P A van Eijk  6 , U Santamaria  1 , M-L Rogers  7 , A Malaspina  8 , V Lombardi  8 , P R Mehta  9 , H-J Westeneng  10 , L H van den Berg  10 , A Al-Chalabi  9 , J Gold  11 , A Nath  12
Affiliations

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

M Garcia-Montojo et al. J Neurol Sci. .

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.

Keywords: ALS; Amyotrophic lateral sclerosis; Antiretroviral; HERV-K; HML-2.

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Conflict of interest statement

DISCLOSURES

Authors declare no conflict of interests.

Figures

Fig. 1.
Fig. 1.
Flow diagram of participant enrollment in the Lighthouse trial and HML-2 analysis.
Figure 2:
Figure 2:. Antiretroviral combination therapy decreases HML-2 levels, which correlates with a deceleration in clinical progression.
A) Mean HML-2 ratio as measured by ddPCR at baseline/screening (Pre-treatment) (n=29), at week 4 (n=26), week 8 (n=24), week 16 (n=26), week 20 (n=9) and week 24 of treatment (n=22), and one week after stopping treatment (Post-treatment) (n=23). B) HML-2 ratio at baseline/screening and at week 24. Blue lines represent responders and red lines represent non-responders. C, D and E) Comparison of the percent change in clinical scores from pre-treatment (mean baseline/screening) to week 24 between responders and non-responders. C) Percent change in NPI in responders and non-responders (*P=0.01). D) Percent change in FVC (% predicted) in responders and non-responders. E) Percent change in ALSFRS-R in responders and non-responders.
See this image and copyright information in PMC

Comment in

References

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