NeuroTrans™ Program: Designed to Deliver Therapeutics Across the Blood-brain Barrier

Nearly 1,000 known genetic and neurodegenerative diseases affect the brain. Drugs often have difficulty reaching these disease-affected areas because the brain has evolved a protective barrier, commonly referred to as the blood-brain barrier.

Part of the solution to the medical problem of neurodegenerative diseases is the creation of effective brain targeting and delivery technologies. One of the most obvious ways of delivering therapeutics to the brain is via the brain's extensive vascular network. Treating these diseases by delivering therapeutics into the brain in a minimally invasive way, including through a natural receptor mediated transport mechanism called transcytosis (see sidebar), is a vision shared by both scientists and physicians.

Learn more about NeuroTrans™:

NeuroTrans™ Delivery Across the Blood-brain Barrier

NeuroTrans™ is our proprietary RAP-based technology program to research the delivery of therapeutics across the blood-brain barrier. We believe our NeuroTrans™ platform may provide therapies that will be safer, less intrusive and more effective than current approaches in treating a wide variety of brain disorders.

In preclinical studies, NeuroTrans™ has been conjugated to a variety of protein drugs, including enzymes and growth factors, without interfering with the function of either fusion partner.1 Studies indicate that radio-labeled NeuroTrans™ may be transcytosed across the blood-brain barrier and, that fusions between NeuroTrans™ and therapeutic proteins may be manufactured economically.2

Research Collaboration and License Agreement with Roche

In June 2009, Raptor entered a collaboration and licensing agreement with Roche to evaluate therapeutic delivery of select molecules attached to Raptor’s proprietary NeuroTrans™ blood-brain barrier (“BBB”) transporter platform. The license gives Roche an exclusive worldwide license to NeuroTrans™ for use in the delivery of diagnostic and therapeutic molecules across the blood-brain barrier. Roche’s and Raptor’s scientists will actively collaborate on the project. Raptor received an initial upfront payment to fund the initial stage of the collaboration and is eligible for future collaboration support, development milestone payments and net sales royalties from Roche.

Research Collaboration with Stanford University

We worked with Dr. William Mobley, while he was professor and Chairman of the Department of Neurology and Neurological Sciences, and his lab at Stanford University to study the brain transport behavior of NeuroTrans™ candidates.

In the first year of our collaboration, a number of RAP-based peptide transport candidates were tested for their ability to bind to receptors that are thought to reside on the cells that line the blood-brain barrier. From these experiments, a lead candidate peptide was selected. In the second year of our collaboration, we completed preclinical evaluations which we believe support that NeuroTrans™ conjugates injected into the blood stream have the ability to seek out, bind to, and rapidly enter the cells that line the blood-brain barrier. These experiments support the NeuroTrans™ peptide's ability to enhance the transport of cargo molecules into the cells that line the blood-brain barrier. This collaboration has lapsed.

Learn more about Raptor's other preclinical programs:

References:

  1. Prince WS, McCormick LM, Wendt DJ, Fitzpatrick PA, Schwartz KL, Aguilera AI, Koppaka V, Christianson TM, Vellard MC, Pavloff N, Lemontt JF, Qin M, Starr CM, Bu G, Zankel TC. Lipoprotein receptor binding, cellular uptake, and lysosomal delivery of fusions between the receptor-associated protein (RAP) and alpha-L-iduronidase or acid alpha-glucosidase. J Biol Chem. 2004 Aug 13;279(33):35037-46.
  2. Pan W, Kastin AJ, Zankel TC, van Kerkhoff P, Terasaki T, Bu G. Efficient transfer of RAP across the blood-brain barrier. J Cell Sci. 2004;117:5071-5078.