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

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:423

Article

Garcia-Montojo, M.¹  Fathi, S.¹  Smith, B. R.¹  Rowe, D. B.^1,2  Kiernan, M. C.^3,4  Vucic, S.⁵  Mathers, S.⁶  van Eijk, R. P. A.^7,8  Santamaria, U.¹  Rogers, M. -L.⁹  Malaspina, A.¹⁰  Lombardi, V.¹⁰  Mehta, P. R.^11,12  Westeneng, H. -J.⁷  van den Berg, L. H.⁷  Al-Chalabi, A.^11,12  Gold, J.^10,11,13,14  Nath, A.¹ 

[1] NINDS, Sect Infect Nervous Syst, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[2] Macquarie Univ, Ctr Motor Neuron Dis Res, Dept Clin Med, N Ryde, NSW, Australia

[3] Univ Sydney, Brain & Mind Ctr, Sydney, NSW, Australia

[4] Royal Prince Alfred Hosp, Dept Neurol, Sydney, NSW, Australia

[5] Univ Sydney, Westmead Hosp, Dept Neurol, Sydney, NSW, Australia

[6] Calvary Hlth Care Bethlehem, Dept Neurol, Melbourne, Vic, Australia

[7] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol, Utrecht, Netherlands

[8] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Biostat & Res Support, Utrecht, Netherlands

[9] Flinders Univ S Australia, Fac Med & Publ Hlth, Ctr Neurosci, Adelaide, SA, Australia

[10] Queen Mary Univ London, Blizard Inst, London, England

[11] Kings Coll London, Maurice Wohl Clin Neurosci Inst, Dept Basic & Clin Neurosci, London SE5 9RX, England

[12] Kings Coll Hosp London, Dept Neurol, London SE5 9RS, England

[13] Univ Sydney, Albion Ctr, Sydney, NSW, Australia

[14] Univ Sydney, Fac Med & Hlth, Sydney, NSW, Australia

关键词: Amyotrophic lateral sclerosis;    ALS;    HERV-K;    HML-2;    Antiretroviral;   

DOI  :  10.1016/j.jns.2021.117358

来源: Elsevier

【 摘 要 】

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 pretreatment 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.

【 授权许可】

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