Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6)

TY - JOUR

T1 - Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6)

AU - Ufer, Friederike

AU - Ziegler, Susanne M

AU - Altfeld, Marcus

AU - Friese, Manuel A

N1 - Copyright © 2023 Ufer, Ziegler, Altfeld and Friese.

PY - 2023

Y1 - 2023

N2 - INTRODUCTION: Autosomal dominant mutations in the C-terminal part of TREX1 (pVAL235Glyfs*6) result in fatal retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) without any treatment options. Here, we report on a treatment of a RVCLS patient with anti-retroviral drugs and the janus kinase (JAK) inhibitor ruxolitinib.METHODS: We collected clinical data of an extended family with RVCLS (TREX1 pVAL235Glyfs*6). Within this family we identified a 45-year-old woman as index patient that we treated experimentally for 5 years and prospectively collected clinical, laboratory and imaging data.RESULTS: We report clinical details from 29 family members with 17 of them showing RVCLS symptoms. Treatment of the index patient with ruxolitinib for >4 years was well-tolerated and clinically stabilized RVCLS activity. Moreover, we noticed normalization of initially elevated CXCL10 mRNA in peripheral blood monocular cells (PBMCs) and a reduction of antinuclear autoantibodies.DISCUSSION: We provide evidence that JAK inhibition as RVCLS treatment appears safe and could slow clinical worsening in symptomatic adults. These results encourage further use of JAK inhibitors in affected individuals together with monitoring of CXCL10 transcripts in PBMCs as useful biomarker of disease activity.

AB - INTRODUCTION: Autosomal dominant mutations in the C-terminal part of TREX1 (pVAL235Glyfs*6) result in fatal retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) without any treatment options. Here, we report on a treatment of a RVCLS patient with anti-retroviral drugs and the janus kinase (JAK) inhibitor ruxolitinib.METHODS: We collected clinical data of an extended family with RVCLS (TREX1 pVAL235Glyfs*6). Within this family we identified a 45-year-old woman as index patient that we treated experimentally for 5 years and prospectively collected clinical, laboratory and imaging data.RESULTS: We report clinical details from 29 family members with 17 of them showing RVCLS symptoms. Treatment of the index patient with ruxolitinib for >4 years was well-tolerated and clinically stabilized RVCLS activity. Moreover, we noticed normalization of initially elevated CXCL10 mRNA in peripheral blood monocular cells (PBMCs) and a reduction of antinuclear autoantibodies.DISCUSSION: We provide evidence that JAK inhibition as RVCLS treatment appears safe and could slow clinical worsening in symptomatic adults. These results encourage further use of JAK inhibitors in affected individuals together with monitoring of CXCL10 transcripts in PBMCs as useful biomarker of disease activity.

U2 - 10.3389/fneur.2023.1118369

DO - 10.3389/fneur.2023.1118369

M3 - Case report

C2 - 36895907

VL - 14

JO - FRONT NEUROL

JF - FRONT NEUROL

SN - 1664-2295

M1 - 1118369

ER -