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Barriers & Molecular Regulators

The fourth STEP concentrated on overcoming barriers for regeneration and repair. As our scientific knowledge has progressed, it is clear that various molecules originating from inflammatory cells or the breakdown of myelin may inhibit axonal growth and lead to unsuccessful regeneration. Thus, Miami Project scientists have focused on identifying molecules that may help to overcome or target these inhibitory factors in both cell culture as well as animal models. In 2006, we organized a High Content Screening core to help identify novel molecules that promote successful axonal growth under conditions where inhibitory factors normally retard that growth. Indeed, lead compounds have now been translated to more complex models of SCI and are providing exciting information regarding what molecules are responsible for successful and unsuccessful axonal growth and which may be targets for treatment strategies. Junior, established, and senior scientists are working together to help understand the basic science of axon repair with the long term goal of using this knowledge to define the future of repairing the nervous system after injury.

The Miami Project continues to grow by recruiting the next generation of outstanding scientists dedicated to paralysis research. New technologies and approaches are allowing our programs to branch out into different areas of human medicine that may help provide answers to this complex problem. For example, in addition to the importance of studying extrinsic mechanisms underlying the control of successful regeneration, new research is targeting endogenous or intrinsic mechanisms that may limit reparative processes in the mature nervous system. Novel molecules and molecular targets are being identified that appear to be are critical regulators of axonal growth that have never been investigated.

In addition, new information is being obtained on the molecular control mechanisms for promoting neurogenesis and neovascularization in the injured brain and spinal cord. Ultimately, the use of cell therapies combined with clinically relevant strategies to alter these molecular regulators of regeneration, synaptic function and repair may be an important therapeutic strategy to consider in future FDA applications.