Investigation of intrathecal transport of NPT002, a prospective therapeutic based on phage M13, in nonhuman primates

Drug Delivery and Translational Research
Mikhail I PapisovC Gillooly

Abstract

Presently, there are no effective treatments for conditions characterized by protein misfolding, such as Alzheimer's, Parkinson's, and other diseases involving CNS. Since misfolding occurs at the earliest stage of the disease, it is likely to be involved in subsequent pathological developments. It has been found that NPT002 (bacteriophage M13) directly dissociates aggregates of misfolded proteins that form amyloid, including amyloid-β, tau and α-synuclein. For CNS applications, NPT002 requires delivery to the brain parenchyma, the target tissue. NPT002 is an elongated ~950 nm particle that cannot penetrate into the brain from the blood. Furthermore, phage particles, due to their size, cannot be effectively transported in vivo by diffusion. Considering the physiology of the leptomeningeal space, intrathecal administration appears to be a promising convection-driven avenue for NPT002 delivery. In this paper, we use positron emission tomography to investigate the transport of NPT002 in Macaca fascicularis. The data suggest that approximately 50 % of the administered dose can reach the cerebral leptomeningeal space after a single lumbar intrathecal injection. A biologically significant fraction of the phage then enters the brain, r...Continue Reading

References

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Mar 3, 2011·Molecular Pharmaceutics·Vasily V BelovMikhail I Papisov
Jun 1, 2012·Drug Delivery and Translational Research·Mikhail I PapisovC Gillooly

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Citations

Jan 16, 2013·Molecular Pharmaceutics·Mikhail I PapisovKimberley S Gannon
Jul 13, 2018·JCI Insight·Geir RingstadPer K Eide
Jun 14, 2019·Frontiers in Neuroscience·Beata DurcanovaMikhail Papisov
Mar 7, 2020·Advanced Drug Delivery Reviews·M J FowlerR W Sirianni
May 4, 2021·Frontiers in Neuroscience·Vasily BelovMikhail Papisov

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