The scientific program for the 10th annual Brains for Brain meeting is now up. Reinhard Gabathuler presents on Saturday March 19th.

ADMINISTRATION OF FUSION PROTEINS INCORPORATING MTFPEP OR MTF IN A LYSOSOMAL ENZYME (I2S) DELIVERS A THERAPEUTICAL CONCENTRATION OF I2S TO THE CNS TO TREAT MPS II (HUNTER SYNDROME)

biOasis Technologies Inc. is a biopharmaceutical company focused on the treatment of CNS diseases and disorders. The Company is developing proprietary peptide vectors based on melanotransferrin (MTf) for the delivery of therapeutics to the CNS, this platform is called “Transcend”.

Drug delivery into the CNS remains a significant challenge for clinical neuroscientists as most drugs show limited penetration in the CNS due to the blood-brain barrier (BBB). The BBB characteristics provide a natural defense against toxic or infective agents circulating in the blood. Therefore, the development of new technologies to cross the BBB for brain parenchyma uptake is of great interest and vital importance for the treatments of neurological disorders and genetic diseases. A family of vectors called Transcend, comprising the full-length MTf and peptides thereof, are developed by biOasis Technologies Inc. to facilitate receptor-mediated drug delivery into the brain to treat CNS disorders.

We have previously shown that lysosomal enzymes, as iduronate 2-sulfatase (I2S), labeled with fluorescent dyes are transported across the BBB in the lysosome of brain cells when incorporating MTf or MTfpep (12 amino-acid peptide) in a fusion protein.

Studies addressing the brain delivery of I2S for the treatment of Hunter Syndrome in k/o mice have shown efficacy in reducing significantly the amount of lysosomal storage in brain cells. Two fusion proteins, composed of I2S incorporating MTf or MTfpep, were administered in k/o mice. High induced I2S activity first shown in an in-vitro assay, was confirmed by the decrease of total GAG content in liver and urine, to wild-type mice level. These data were further confirmed by the analysis of heparan sulfate level in liver, performed by MS technology. Analysis and quantification of organel-les in brain cells have shown significant decrease of the amount of vacuoles and lysosomes demonstrating a therapeutic concentration of lysosomal enzymes reaching the brain parenchyma. These data will be further discussed in the presentation.

Results show additional application of our platform technology and demonstrate that MTfpep can be used as a carrier capable of shuttling a variety of compounds, ranging from small anti-cancer agents to larger biologics, across the BBB into the brain parenchyma in therapeutic doses, enabling treatment of neurological disorders.