The Rowett nude rat ([Crl:NIH-Foxn1.sup.rnu]) has no thymus and therefore does not raise a Tcell-dependent antibody response against foreign proteins .
The purpose of the current studies was to evaluate the long-term toxicity of N8-GP when administered intravenously once every fourth day to Rowett nude rats for 52 weeks (followed by a 12-week recovery period).
The Rowett nude rats ([Crl:NIHFoxn1.sup.rnu]) were supplied by Charles River (USA and Germany) and were acclimatized for >12 days before dosing began.
For each assay, a cut point value was calculated as the mean + [t(0.05; 1-sided; df) * SD] of 18 plasma samples from untreated healthy Rowett nude rats.
No PEG was detected in the choroid plexus using IHC staining and, in the absence of any adverse findings in these studies, the level of no observed adverse effect in Rowett nude rats was considered to be N8GP 1200 IU/kg, dosed every fourth day.
The immune-deficient Rowett nude rat has been proven to be a suitable model for long-term toxicity studies in the current studies and in our previous study with N9-GP .
The Rowett nude rat was used because of its impaired ability to mount an immune response and hence generate ADAs that could alter the clearance of N8-GP and reduce N8-GP exposure.
These findings expand our knowledge of the N8-GP molecule, the safety of glycoPEGylation as a protraction technology, and the Rowett nude rat as a model for long-term toxicity studies.
Offenberg, "Evaluation of nonacog beta pegol long-term safety in the immune-deficient rowett nude rat (Crl:NIH-Foxn1rnu)," Toxicologic Pathology, vol.