CD-RAP and Palovarotene Lab Meeting 3/18/2014

Palovarotene A retinoic acid receptor gamma (RARγ) agonist Inhibits cartilage formation During development, new bone formation is stimulated by a drop in retinoid signaling RARγ agonists maintain retinoid signaling preventing new bone formation Has been shown to prevent HO formation

B Palovarotene (mg/kg) C A Palovarotene (mg/kg) n = 16 n = 8 n = 16 n = 8n = 9

CD-RAP CD-Rap is expressed during chondrogenesis A plasma biomarker for cartilage formation – Observed to be elevated in patients with: Neurofibromatosis type I Rheumatoid Arthritis During fracture healing Marathon runners

Rationale – A circulating biomarker provides an additional metric for the efficacy of a treatment – A particular drug may not improve function but may result in lower biomarker levels suggesting that the class of drug may hold promise

Methods Plasma samples from mice and patients ELISA – Mouse: Kit from CUSABIO – Human: Kits from Roche and CUSABIO

D0D2D5D7D10D14 CON PAL * * Palovarotene treatment results in lower CD-RAP levels

Human CD-RAP ELISA

Conclusion and continuing work CD-RAP shows promise as a circulating biomarker for HO formation Repeat mouse CD-RAP ELISA – Increase number of samples to 8 at each time point Repeat human CD-RAP ELISA – More samples for each group – Repeat with first kit tested at higher plasma concentration