GM1-gangliosidosis is a lysosomal disease resulting from a deficiency in the hydrolase β-galactosidase (β-gal) and subsequent accumulation of gangliosides, primarily in neuronal tissue, leading to progressive neurological deterioration and eventually early death. Lysosomal diseases with neurological involvement have limited non-invasive therapies due to the inability of lysosomal enzymes to cross the blood-brain barrier (BBB). A novel fusion enzyme, labeled mTfR-GLB1, was designed to act as a ferry across the BBB by fusing β-gal to the mouse monoclonal antibody against the mouse transferrin receptor and tested in a murine model of GM1-gangliosidosis (β-gal^−/−). Twelve hours following a single intravenous dose of mTfR-GLB1 (5.0 mg/kg) into adult β-gal^−/− mice showed clearance of enzyme activity in the plasma and an increase in β-gal enzyme activity in the liver and spleen. Long-term efficacy of mTfR-GLB1 was assessed by treating β-gal^−/− mice intravenously twice a week with a low (2.5 mg/kg) or high (5.0 mg/kg) dose of mTfR-GLB1 for 17 weeks. Long-term studies showed high dose mice gained weight normally compared to vehicle-treated β-gal^−/− mice, which are significantly heavier than heterozygous controls. Behavioral assessment at six months of age using the pole test showed β-gal^−/− mice treated with mTfR-GLB1 had improved motor function. Biochemical analysis showed an increase in β-gal enzyme activity in the high dose group from negligible levels to 20% and 11% of heterozygous levels in the liver and spleen, respectively. Together, these data show that mTfR-GLB1 is a catalytically active β-gal fusion enzyme in vivo that is readily taken up into tissues.

Despite these indications of bioactivity, behavior tests other than the pole test, including the Barnes maze, inverted screen, and accelerating rotarod, showed limited or no improvement of treated mice compared to β-gal^−/− mice receiving vehicle only. Further, administration of mTfR-GLB1 was insufficient to create measurable increases in β-gal enzyme activity in the brain or reduce ganglioside content (biochemically and morphologically).

GM1神经节苷脂病是一种溶酶体疾病，是由于水解酶β-半乳糖苷酶（β-gal）缺乏和随后神经节苷脂（主要在神经元组织中）蓄积而导致进行性神经学恶化并最终早期死亡。由于溶酶体酶无法穿越血脑屏障（BBB），因此具有神经系统疾病的溶酶体疾病的非侵入性治疗方法受到限制。一种新型的融合酶，标记的mTfR-GLB1，被设计成用作通过融合的β-gal对针对小鼠转铁蛋白受体的鼠单克隆抗体和在GM1神经节苷脂（β半乳糖苷酶的鼠模型测试穿过BBB渡船^{- / −}）。将单次静脉注射mTfR-GLB1（5.0 mg / kg）注入成年β-gal ^-/-后的12小时小鼠表现出血浆中酶活性的清除以及肝脏和脾脏中β-gal酶活性的增加。通过每周两次用低剂量（2.5 mg / kg）或高剂量（5.0 mg / kg）的mTfR-GLB1静脉内治疗β-gal ^-/-小鼠17周来评估mTfR-GLB1的长期疗效。长期研究表明，与经媒介物处理的β-gal ^-/-小鼠相比，高剂量小鼠的体重正常增加，而这些小鼠明显比杂合对照重。使用极点测试在六个月大时进行的行为评估显示，β-gal ^-/-用mTfR-GLB1处理的小鼠的运动功能得到改善。生化分析表明，高剂量组的β-gal酶活性从可忽略不计的水平增加到肝脏和脾脏杂合水平的20％和11％。这些数据在一起表明，mTfR-GLB1是体内具有催化活性的β-gal融合酶，很容易吸收到组织中。

尽管有这些生物活性的指示，但与极点测试不同的行为测试（包括Barnes迷宫，倒置屏幕和加速旋转脚踏车）与仅接受赋形剂的β-gal ^-/-小鼠相比，治疗小鼠的改善有限或没有改善。此外，施用mTfR-GLB1不足以在大脑中产生可测量的β-gal酶活性增加或降低神经节苷脂含量（从生物化学和形态上）。