Evaluation of efficacy and bio-distribution of AAV5-miHTT in HD minipig brain

0472243 - ÚŽFG 2017 RIV CZ eng V - Výzkumná zpráva
Bohuslavová, Božena - Juhás, Štefan - Juhásová, Jana - Ellederová, Zdeňka - Motlík, Jan
Evaluation of efficacy and bio-distribution of AAV5-miHTT in HD minipig brain.
Liběchov: UniQure, 2016. 204 s.
Zdroj financování: N - neveřejné zdroje
Klíčová slova: minipig * Huntington´s disease
Kód oboru RIV: EB - Genetika a molekulární biologie

Healthy minipigs (n=29) were pre-screened for serum AAV5 neutralizing antibodies (NABs) in serum by uniQure. Conclusions: Intrastriatal/intrathalamic bilateral application of AAV5-CAG-miHtt(3e13/1e13gctotal) or PBS/Sucrose (54μl/216μl) similarly to AA5-CAG-GFP didn´t cause any neurological deficit in transgenic as well as wild type animals. The body weight increased in all animals 84 days after AAV5-CAG-miHtt/PBS-Sucroseintrastriatal/intrathalamic delivery with two exceptions TGanimal L616 (AAV5-CAG-miHtt1e 13g ctotal) and WTanimal L485 (AAV5-CAG-miHtt3e13gc total). The TG boar N176 from group VII (PBS/Sucrose) died during narcosis 56 days after IP/IT application), shortly after CSF and blood collection.The boar breathed heavily and intermittently, then the heart stopped beat and resuscitation failed. We immediately flushed them by 20 L of PBS with heparin and collect all tissues. All animals had normal food consumption. Inflammatory proces in AAV5-CAG-miHtt (1e13 gc total) seems to be similar to PBS/Sucrose injected animals accompanied with no detectable histological pathologies.
Trvalý link: http://hdl.handle.net/11104/0269546