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Primary Sjögren's syndrome and high type I interferon signalling in a kindred with C2 deficiency.
Willemsen M, Van Nieuwenhove E, Seyed Tabib NS, Staels F, Schrijvers R, De Somer L, Liston A, Humblet-Baron S, Wouters C
n/a
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Rheumatology advances in practice,
6,
1,
2022
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AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model.
Marino M, Zhou L, Rincon MY, Callaerts-Vegh Z, Verhaert J, Wahis J, Creemers E, Yshii L, Wierda K, Saito T, Marneffe C, Voytyuk I, Wouters Y, Dewilde M, Duqué SI, Vincke C, Levites Y, Golde TE, Saido TC, Muyldermans S, Liston A, De Strooper B, Holt MG
Single domain antibodies (VHHs) are potentially disruptive therapeutics, with important biological value for treatment of several diseases, including neurological disorders. However, VHHs have not been widely used in the central nervous system (CNS), largely because of their restricted blood-brain barrier (BBB) penetration. Here, we propose a gene transfer strategy based on BBB-crossing adeno-associated virus (AAV)-based vectors to deliver VHH directly into the CNS. As a proof-of-concept, we explored the potential of AAV-delivered VHH to inhibit BACE1, a well-characterized target in Alzheimer's disease. First, we generated a panel of VHHs targeting BACE1, one of which, VHH-B9, shows high selectivity for BACE1 and efficacy in lowering BACE1 activity in vitro. We further demonstrate that a single systemic dose of AAV-VHH-B9 produces positive long-term (12 months plus) effects on amyloid load, neuroinflammation, synaptic function, and cognitive performance, in the App Alzheimer's mouse model. These results constitute a novel therapeutic approach for neurodegenerative diseases, which is applicable to a range of CNS disease targets.
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EMBO molecular medicine,
14,
4,
07 Apr 2022
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Role for G-CSF in neutrophilic extramedullary myelopoiesis in a murine model of systemic juvenile idiopathic arthritis.
Malengier-Devlies B, Bernaerts E, Ahmadzadeh K, Filtjens J, Vandenhaute J, Boeckx B, Burton O, De Visscher A, Mitera T, Berghmans N, Verbeke G, Liston A, Lambrechts D, Proost P, Wouters C, Matthys P
Systemic juvenile idiopathic arthritis (sJIA) is a systemic inflammatory disease of childhood-onset. sJIA is associated with neutrophilia, including immature granulocytes, potentially driven by the growth factor granulocyte-colony stimulating factor (G-CSF). This study aimed to unravel the role of G-CSF in the pathology of sJIA.
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Arthritis & rheumatology (Hoboken, N.J.),
1,
1,
03 Mar 2022
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