Visualization of the therapeutic efficacy of a gene correction approach in Wilson’s disease by laser-ablation inductively coupled mass spectrometry

Laser Ablation Inductively Coupled Plasma Spectrometry: Metal Imaging in Experimental and Clinical Wilson Disease

“…progression of WD, and further verifies that LA-ICP-MSI is a highly potent technology, strengthening the explanatory power of therapeutic success in such curative studies [43]. In addition, these findings fully confirm the previous atomic absorption spectroscopic measurements and the Timm's sulfide silver stainings showing a reduction in hepatic Cu accumulation after treatment with AAV8-AAT-ATP7B [49].…”

“…The removal of Cu was further associated with a simultaneous decrease in hepatic Fe, a slight loss in hepatic Zn, reduced urinary copper excretion, increased ceruloplasmin activity, and lower activity of alanine aminotransaminase. All these parameters indicate that this gene therapeutic approach is suitable to abrogate and reverse hepatic alterations occurring during the progression of WD, and further verifies that LA-ICP-MSI is a highly potent technology, strengthening the explanatory power of therapeutic success in such curative studies [43]. In addition, these findings fully confirm the previous atomic absorption spectroscopic measurements and the Timm's sulfide silver stainings showing a reduction in hepatic Cu accumulation after treatment with AAV8-AAT-ATP7B [49].…”

“…Similarly, a significant flush-out of Cu from hepatic tissue in Atp7b −/− mice was observed after therapeutic treatment with an adeno-associated virus serotype 8 encoding a therapeutically effective mini version of the human ATP7B gene placed under transcriptional control of the liver-specific α1-antitrypsin gene promoter [43]. A single treatment with this gene vector was already sufficient to decrease the Cu content to 43.3 ± 3.6 µg/g, while the untreated controls had values of 112.7 ± 13.3 µg/g liver tissue ( Figure 7) with coefficient of variation (CV) in measurements that were in the range of 8.3-11.8% [43]. The removal of Cu was further associated with a simultaneous decrease in hepatic Fe, a slight loss in hepatic Zn, reduced urinary copper excretion, increased ceruloplasmin activity, and lower activity of alanine aminotransaminase.…”

“…Additional samples from brain and liver of mice subjected to gene therapy (Figures 7 and 8) were kindly provided by Gloria González-Aseguinolaza and Ruben Hernández-Alcoceba from the University of Navarra, Pamplona, Spain. For this review, new images were generated from data sets published before [38,43,44]. Therefore, no additional animal experimentation was required for this review.…”

“…For orientation, light microscopic (LM) images of respective cryosections before subjecting to LA-ICP-MSI procedure are depicted. More details of this study are given elsewhere[43,49].Inorganics 2019, 7, x FOR PEER REVIEW 12 of 20…”