Naslov
New way to treat bone loss: a novel anabolic targeted therapy – BONE6-BIS

Autori
Pećina M, Verbanac D, Martinić M, Grgurević L, Brkljačić J, Vukičević S.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Skup
34th SICOT Orthopaedic World Congress

Mjesto i datum
Hyderābād, Indija, 17.10.2013. - 19.10.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
osteoporosis; BMP6; bisphosphonate

Sažetak
We have developed a new therapeutic concept for the treatment of osteoporosis namedBONE6-BIS. This new therapeutic option will have better efficacy and safety profile in respect to the existing therapies. Novelty is related to “chimeric” molecule consisting of bone morphogenetic protein 6 (BMP6) and a bisphosphonate, linked by specific coupling chemistry. Bisphosphonate (BP), as a small molecule, directs BMP6 toward the site of action –bone surface, where BMP6 acts as anabolic factor. We have produced BMP6 in mammalian cell culture as a dimer with a large pro-domain. The pro-domain itself has neither bone inducing activity nor does it block the osteogenic activity of mature BMP6, but is stable and is used for purification of the mature BMP6 protein. The respective coupling chemistry involves conjugation of the bisphosphonate to the aminogroups of lysine residues in the BMP6. By applying newly, in-house developed techniques we were able to confirm 5 out of 14 potential BP coupling sites in the pro-domain and all 7 potential coupling sites in the mature domain of the BMP6. In addition, we have shown that trypsin readily generates BMP6 peptides which were detected by sophisticated LCMS measurements. Coupling with Alendronate which has been selected as the most suitable BP is currently ongoing, after which the “chimeric” molecule will be ready for preliminary testing. In parallel, we thoroughly investigate by in vitro and in vivo experiments, specific molecular mechanisms and mode of action by which BMP6 induces formation of new

Izvorni jezik
Engleski

POVEZANOST RADA