Optimization of extracellular production of recombinant human bone morphogenetic protein-7 (rhBMP-7) with Bacillus subtilis.
OBJECTIVE To review the uses of bone morphogenetic proteins (BMPs) and BMP gene therapy for the treatment of neurosurgical disorders. METHODS Literature review. RESULTS BMPs are members of the transforming growth factor beta superfamily, and they play an important role in the growth and development of numerous tissues, including bone, brain, and spinal cord. Although the majority of previous studies have focused on the regulatory functions of BMPs in the normal growth and differentiation of the skeletal system, BMPs also seem to be exquisitely involved in the regulation of cellular proliferation, survival, differentiation, apoptosis, and lineage commitment in the central nervous system. When specific BMPs are delivered on biological matrices, they have the capacity to induce bone, cartilage, ligament, and tendon at both heterotopic and orthotopic sites, suggesting that they may play a major role in the future treatment of spinal and craniofacial pathology. For example, recent studies have clearly demonstrated the usefulness of BMPs and BMP gene therapy for the induction of spinal arthrodesis in several animal models. In addition, several BMPs have been shown to have a neuroprotective effect in animal models of head injury, cerebral ischemia, and Parkinson's disease and may therefore have direct clinical applications for the treatment of central nervous system disorders. CONCLUSION As the physiological activity of BMPs in the development and pathology of the central nervous system and spine are more fully elucidated, BMP therapeutics and gene therapy will probably have numerous applications in neurological surgery.