Methods and Compositions for Treating Lysosomal Storage Diseases

Recombinant AAV serotype 6 (rAAV6) is used to deliver the human lysosomal alpha-mannosidase (LAMAN) (MAN2B) cDNA sequence to the choroid plexus epithelia. This approach is designed to replace the missing lysosomal enzyme, LAMAN in the brain and thereby avert lethal neurodegenerative processes that follow from defects in lysosomal storage and metabolism. Preclinical experiments in a mouse model have demonstrated restoration of LAMAN to normal or near-normal levels globally throughout the brain, after specific and selective transduction of choroid plexus. Additional preclinical development, including large animal testing and GMP manufacturing of the viral vector will be needed to support an investigational new drug (IND) application and a first-in-human clinical trial. This technology may be applicable to numerous other lysosomal storage diseases involving the central nervous system (CNS).Researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have demonstrated that lateral ventricle administration of recombinant adeno-associated virus serotype 5 (rAAV5) resulted in selective gene transfer to the choroid plexus epithelia – and provided treatment benefit in a mouse model of Menkes disease, a lethal pediatric disorder of copper transport. Subsequently, we assessed the feasibility of targeting choroid plexus epithelia with rAAV gene therapy vectors for treatment of a broader category of neurometabolic diseases, lysos omal storag...

Source: NIH OTT Licensing Opportunities - July 20, 2018 Category: Research Authors: ajoyprabhu3 Source Type: research