Targeted Bone Regeneration via Activation of Resident Stem Cells

National Center For Advancing Translational Sciences

Investigators

Abstract

Recombinant proteins have short half-lives, requiring large doses that can lead to inflammation and other unwanted side effects. To overcome the limitations of current treatments, the lead collaborators developed a new technology, called SonoHeal, that attracts and activates endogenous tissue stem cells to regenerate bone and heal fractures. First, a biodegradable scaffold is implanted into the fracture site, which recruits the patients own mesenchymal stem cells (MSCs). At a second step, BMP-6 plasmid is delivered to the MSCs via sonoporation the use of transcutaneous ultrasound to transfer plasmid DNA across the cell membrane resulting in BMP-6 protein expression at a physiological level to induce cell differentiation and promote the formation of new bone and fracture healing. TDB scientists are continuing preclinical development efforts to advance the SonoHeal technology to clinical evaluation. The team completed an in vivo efficacy study, developed a human BMP-6 bioanalytical method, and manufactured the clinical grade injectable drug product (pCMV-BMP-6) to be used in subsequent human trials. Ongoing activities include continued development of additional bioanalytical methods and analyses of samples to support GLP toxicology studies, pharmacokinetic biodistribution studies, and evaluation of anti-drug antibodies. Completion of these activities will enable the collaborators to file an Investigational New Drug (IND) application to the Food and Drug Administration (FDA).