Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Cluster of Excellence NeuroCure, Berlin, Germany.
Sci Rep. 2018 Apr 4;8(1):5648. doi: 10.1038/s41598-018-23949-4.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disorder, which causes progressive sensory and motor deficits and often results in severe disability. Knockout of the co-stimulatory protein CD86 in mice of the non-obese diabetic background (NoD.129S4-Cd86 /JbsJ) results in the development of a spontaneous autoimmune peripheral polyneuropathy (SAPP). We used this previously described transgenic model to study the effects of the sphingosine-1-phosphate receptor agonist fingolimod on SAPP symptoms, functional and electrophysiological characteristics. Compared to two control strains, knockout of CD86 in NOD mice (CD86 NOD) resulted in progressive paralysis with distinct locomotor deficits due to a severe sensory-motor axonal-demyelinating polyneuropathy as assessed by electrophysiological measurements. We started fingolimod treatment when CD86 NOD mice showed signs of unilateral hind limb weakness and continued at a dose of 1 mg/kg/day for eight weeks. We did not observe any beneficial effects of fingolimod regarding disease progression. In addition, fingolimod did not influence the functional outcome of CD86 NOD mice compared to vehicle treatment nor any of the electrophysiological characteristics. In summary, we show that fingolimod treatment has no beneficial effects in autoimmune polyneuropathy, which is in line with recent clinical data obtained in CIDP patients.
慢性炎症性脱髓鞘性多发性神经病（CIDP）是一种自身免疫性疾病，可导致进行性感觉和运动功能障碍，常导致严重残疾。敲除非肥胖型糖尿病（NOD）背景下的小鼠协同刺激蛋白 CD86（NoD.129S4-Cd86 /JbsJ）可导致自发性自身免疫性周围多发性神经病（SAPP）的发生。我们使用这种先前描述的转基因模型来研究鞘氨醇-1-磷酸受体激动剂 fingolimod 对 SAPP 症状、功能和电生理特征的影响。与两种对照品系相比，NOD 小鼠的 CD86 敲除（CD86 NOD）导致进行性瘫痪，由于严重的感觉运动轴突脱髓鞘多发性神经病，导致明显的运动缺陷，通过电生理测量进行评估。当 CD86 NOD 小鼠出现单侧后肢无力迹象时，我们开始使用 fingolimod 治疗，每天剂量为 1mg/kg，持续 8 周。我们没有观察到 fingolimod 在疾病进展方面有任何有益的影响。此外，与 vehicle 治疗相比，fingolimod 对 CD86 NOD 小鼠的功能结果没有影响，也没有影响任何电生理特征。总之，我们表明 fingolimod 治疗在自身免疫性多发性神经病中没有有益的影响，这与最近 CIDP 患者的临床数据一致。
