TeeleOstin Pharmaceuticals has tested the activity of fish PTH using both in vitro and in vivo assays.

In vitro Assays

The adenylate cyclase bioassay was used to test fPTH in vitro. This assay is used to measure the ability of an osteoblast cell line to produce cAMP when exposed to parathyroid hormone and is the gold standard in vitro assay for the measurement of bone formation. fPTH was found to have greater maximal effect than hPTH. However, hPTH reached this maximal efficacy at lower concentrations than fPTH.

In vivo Studies

Teeleostin Pharmaceuticals has completed a preliminary animal study in juvenile rats to compare the ability of fPTH to hPTH in relation to the formation of new bone. These studies revealed that rats treated with fPTH had an increase in the amount and thickness of trabecular bone and trabecular number. This effect was seen at low doses and an higher doses, the secondary spongiosa was also increased. fPTH was shown to be less effective than the equivalent dose of hPTH. However, because of the maximal effect of fPTH in the adenylate cyclase assay, TeeleOstin Pharmaceuticals believes that fPTH has the ability to outperform hPTH at higher doses (than those that were used in this preliminary study). TeeleOstin Pharmaceuticals has commenced a further animal study to optimise the dose of fPTH.

Bone sections from juvenile rat study

TeeleOstin Pharmaceuticals ongoing R&D program will focus on the completion of certain pre-clinical tests and moving as quickly as possible into clinical trials:

• Acute IV toxicology studies • Acute subcutaneous toxicology studies • 7 day continuous IV toxicology studies • 4 week IV bolus studies • 2 week oral study in rats • Buehler Sensitisation test • Mutagenic activity with S.Typhimurium and E. Coli • Clastogenic activity ± 59 activation • Micronucleus test in bone marrow of CD-1 mice

• Long term carcinogenicity tests • Long term toxicology tests