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CD-RAP and Palovarotene

CD-RAP and Palovarotene. Lab Meeting 3/18/2014. Palovarotene. A retinoic acid receptor gamma (RAR γ ) agonist Inhibits cartilage formation During development, new bone formation is stimulated by a drop in retinoid signaling

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CD-RAP and Palovarotene

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

  2. 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

  3. A B n = 16 0 0 1.47 1.47 2.94 2.94 n = 8 n = 9 Palovarotene (mg/kg) Palovarotene (mg/kg) C n = 8 n = 9 n = 16

  4. 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

  5. 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

  6. Methods • Plasma samples from mice and patients • ELISA • Mouse: Kit from CUSABIO • Human: Kits from Roche and CUSABIO

  7. Palovarotene treatment results in lower CD-RAP levels * *

  8. Human CD-RAP ELISA

  9. 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

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