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

doi:10.1016/j.jns.2021.117358

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

College of Medicine and Public Health

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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.

Original language	English
Article number	117358
Number of pages	6
Journal	Journal of the Neurological Sciences
Volume	423
DOIs	https://doi.org/10.1016/j.jns.2021.117358
Publication status	Published - 15 Apr 2021

Keywords

ALS
Amyotrophic lateral sclerosis
Antiretroviral
HERV-K
HML-2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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. (2021). Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy. Journal of the Neurological Sciences, 423, Article 117358. https://doi.org/10.1016/j.jns.2021.117358

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

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",

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

year = "2021",

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Garcia-Montojo, M, Fathi, S, Norato, G, Smith, BR, Rowe, DB, Kiernan, MC, Vucic, S, Mathers, S, van Eijk, RPA, Santamaria, U, Rogers, ML, Malaspina, A, Lombardi, V, Mehta, PR, Westeneng, HJ, van den Berg, LH, Al-Chalabi, A, Gold, J & Nath, A 2021, 'Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy', Journal of the Neurological Sciences, vol. 423, 117358. https://doi.org/10.1016/j.jns.2021.117358

TY - JOUR

T1 - Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy

AU - Garcia-Montojo, M.

AU - Fathi, S.

AU - Norato, G.

AU - Smith, B. R.

AU - Rowe, D. B.

AU - Kiernan, M. C.

AU - Vucic, S.

AU - Mathers, S.

AU - van Eijk, R. P.A.

AU - Santamaria, U.

AU - Rogers, M. L.

AU - Malaspina, A.

AU - Lombardi, V.

AU - Mehta, P. R.

AU - Westeneng, H. J.

AU - van den Berg, L. H.

AU - Al-Chalabi, A.

AU - Gold, J.

AU - Nath, A.

PY - 2021/4/15

Y1 - 2021/4/15

N2 - 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.

AB - 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.

KW - ALS

KW - Amyotrophic lateral sclerosis

KW - Antiretroviral

KW - HERV-K

KW - HML-2

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DO - 10.1016/j.jns.2021.117358

M3 - Article

C2 - 33653604

AN - SCOPUS:85101675733

SN - 0022-510X

VL - 423

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

M1 - 117358

ER -

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

Abstract

Keywords

UN SDGs

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