Assessing prion infectivity of human urine in sporadic Creutzfeldt-Jakob disease.

Prion diseases are neurodegenerative conditions associated with a misfolded and infectious protein, scrapie prion protein (PrP(Sc)). PrP(Sc) propagate prion diseases within and between species and thus pose risks to public health. Prion infectivity or PrP(Sc) presence has been demonstrated in urine of experimentally infected animals, but there are no recent studies of urine from patients with Creutzfeldt-Jakob disease (CJD). We performed bioassays in transgenic mice expressing human PrP to assess prion infectivity in urine from patients affected by a common subtype of sporadic CJD, sCJDMM1. We tested raw urine and 100-fold concentrated and dialyzed urine and assessed the sensitivity of the bioassay along with the effect of concentration and dialysis on prion infectivity. Intracerebral inoculation of transgenic mice with urine from 3 sCJDMM1 patients failed to demonstrate prion disease transmission, indicating that prion infectivity in urine from sCJDMM1 patients is either not present or is <0.38 infectious units/mL.

Batch-to-batch consistency of human-derived gonadotrophin preparations compared with recombinant preparations.

Different gonadotrophin preparations derived from human urine or manufactured by recombinant technology are currently used in clinical practice for the treatment of infertility. It has been widely assumed that gonadotrophin products manufactured by recombinant technology have better batch-to-batch consistency compared with human-derived preparations and that this potentially will be shown to provide a more constant clinical response, but there is little evidence for either statement. This study compared the batch-to-batch consistency between urinary-derived and recombinant manufactured gonadotrophin preparations using standard analytical techniques, as well as a novel in-vitro follicle bioassay to evaluate the consistency of the biological response at the target organ. Oligosaccharide isoform profiling, immunoassay testing, size exclusion chromatography analysis and in-vitro bioassay testing of urinary derived gonadotrophin preparations (MENOPUR and BRAVELLE) confirm that these products display a high degree of batch-to-batch consistency, similar to recombinant FSH (GONAL-f) either filled by mass or bioassay. The data also suggest that the batch-to-batch variation is independent of the manufacturing procedure (filled-by-bioassay or filled-by-mass) for the recombinant preparation (Gonal-f), but that the total FSH bioactivity delivered from a single dose preparation after reconstitution differs between the two manufacturing procedures.