Nearly 1,000 known genetic and neurodegenerative diseases affect the brain. Drugs often have difficulty reaching areas of the brain affected by diseases because the brain has evolved a protective barrier, commonly referred to as the blood-brain barrier, preventing the free passage of most blood components into the brain. Part of the solution to the medical problem of neurodegenerative diseases is the creation of effective brain targeting and delivery technologies. Treating these diseases by delivering therapeutics into the brain in a minimally invasive way, through a natural receptor mediated transport mechanism called transcytosis, is a vision widely shared by both scientists and physicians. Initially, because of the unmet clinical need, we will focus resources on targeting the delivery of neurotrophic factors such as glial-cell derived neurotrophic factor (GDNF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF), to the brain for the treatment of neurodegenerative diseases. Neurotrophic factors have already demonstrated their potential in treating neurodegenerative diseases, but have not as yet been developed commercially because of the lack of an effective brain.

In practice, attaching drugs to ligands can interfere with the binding of ligands to receptors and attached ligands can diminish the binding of a drug to its target.  However, we have demonstrated that fusion between receptor-associated protein (RAP) and a variety of protein drugs, including enzymes and growth factors, satisfy the requirement that the ligands and drugs do not interfere with each other.  Peer reviewed research papers have shown that RAP is efficiently transcytosed and fusions between RAP and therapeutic proteins have been manufactured using standard methods. Pan, W. et, al. Efficient transfer of RAP across the blood-brain barrier (2004) J Cell Sci 117, 5071-5078; Prince, W. S.et.al. Lipoprotein receptor binding, cellular uptake, and lysosomal delivery of fusions between the RAP and alpha-L-iduronidase or acid alpha-glucosidase (2004) J Biol Chem 279, 35037-35046.

We have named our proprietary RAP technology, developed as a means of transporting therapeutic proteins from the blood to the brain, NeuroTrans™ platform.  We believe our NeuroTrans™ platform provides therapies that will be safer, less intrusive, and more effective than current approaches in treating a wide variety of brain disorders.

Raptor has been working with Dr. William Mobley's lab at Stanford University to study the brain transport behavior of NeuroTrans™ candidates. In the first year of the collaboration, a number of RAP-based peptides were tested for their ability to cross the blood-brain barrier.  From these experiments, a lead candidate was selected.  Moving forward, we plan to continue to assess biodistribution within various brain compartments, commence testing the potential of NeuroTrans™ peptides to deliver NGF across the blood-brain barrier, and investigate the effects of NGF conjugates on the brain in preclinical models.