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

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...

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Veröffentlicht in:Journal of the neurological sciences 2021-04, Vol.423, p.117358-117358, Article 117358
Hauptverfasser: Garcia-Montojo, M., Fathi, S., Norato, G., Smith, B.R., Rowe, D.B., Kiernan, M.C., Vucic, S., Mathers, S., van Eijk, R.P.A., Santamaria, U., Rogers, M.-L., Malaspina, A., Lombardi, V., Mehta, P.R., Westeneng, H.-J., van den Berg, L.H., Al-Chalabi, A., Gold, J., Nath, A.
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •Antiretroviral therapy for 24 weeks decreased HERV-K (HML-2) levels in most patients with ALS.•A rebound in HML-2 levels occurred after discontinuation of the antiretroviral drugs.•Patients that had an antiviral effect against HML-2 showed a trend for slower progression in several clinical parameters.
ISSN:0022-510X
1878-5883
DOI:10.1016/j.jns.2021.117358