PIPELINE | CV-07
CP-BMP2, Bone Healing
No Carrier! Only Simple Injection For Bone Regeneration!
Bone is the only organ that dynamically undergoes continuous tissue remodeling throughout life and is one of the few organs that retains regenerative potential on adult life. Severe damages in bone tissue require local supply of osteogenic growth factors of TGF-β family including bone morphogenetic proteins (BMPs) during regenerative process. Mainly, BMP2 plays an important role in skeletal development and bone formation. Clinical trials with recombinant human (rh) BMP2 protein-based approaches have been applied to promote the healing of severe fractures (e.g., long-bone non-union, tibial fracture implant) and spinal fusion. However, there are a few drawbacks with the use of rhBMP2. Due to short retention time and low tissue integration in a body, ? use of rhBMP2 is expensive with multiple or high-dose of treatment. In addition, rhBMP2 protein-based approaches have numerous side-effects (e.g., ectopic bone formation) at pharmacological dosage and sometimes requires surgical procedure, because it does not have an effective delivery method.
Cell-Permeable BMP2 (CP-BMP2), our TSDT-applied rhBMP2, can be rapidly delivered into neighboring cells and tissues near the injured site by local injection, without a carrier/scaffold or any surgical procedure, and reside in the damaged bone tissue for a longer period, addressing rapid degradation and clearance rate issues that exist with rhBMP2. CP-BMP2 significantly activated Smad osteogenic signaling and induced ALP strongly. In addition, CP-BMP2 showed great persistency and enhanced stability in blood plasma. We also found that CP-BMP significantly promoted bone-regeneration (8 folds higher) in murine calvaria critical-sized defect (Figure 1) and equine hind limb defect models. Utilizing bio-better therapeutics with TSDT, we are developing CP-BMP2 as a next-generation osteogenesis agent to enhance local bone healing in a cost-/patient-friendly way. Shortly, the preclinical studies of CP-BMP2 including toxicity and pharmaco-kinetics/-dynamics are going to proceed.
Figure 1. X-ray result shows the osteogenic efficacy of CP-BMP2 in the mouse calvarial bone defect model