Investigation of intrathecal transport of NPT002, a prospective therapeutic based on phage M13, in nonhuman primates
- Mikhail I. PapisovAffiliated withMassachusetts General HospitalHarvard Medical SchoolShriners Hospitals for Children—Boston Email author
- , V. BelovAffiliated withMassachusetts General HospitalHarvard Medical SchoolShriners Hospitals for Children—Boston
- , E. BelovaAffiliated withMassachusetts General HospitalHarvard Medical SchoolShriners Hospitals for Children—Boston
- , A. J. FischmanAffiliated withHarvard Medical SchoolShriners Hospitals for Children—Boston
- , R. FisherAffiliated withNeuroPhage Pharmaceuticals, Inc.
- , J. L. WrightAffiliated withNeuroPhage Pharmaceuticals, Inc.
- , K. S. GannonAffiliated withNeuroPhage Pharmaceuticals, Inc.
- , J. TitusAffiliated withMassachusetts General Hospital
- , M. GagneAffiliated withMassachusetts General Hospital
- and 1 more
- , C. A. GilloolyAffiliated withMassachusetts General Hospital
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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, resulting in potentially therapeutic cortical and subcortical exposure.
KeywordsBacteriophage M13, NPT002, PET imaging Pharmacokinetics Brain Iodine-124
- Investigation of intrathecal transport of NPT002, a prospective therapeutic based on phage M13, in nonhuman primates
Drug Delivery and Translational Research
Volume 2, Issue 3 , pp 210-221
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- Springer US
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- Bacteriophage M13, NPT002, PET imaging
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- Author Affiliations
- 1. Massachusetts General Hospital, Bartlett Hall 500R, 55 Fruit Street, Boston, MA, 02114, USA
- 2. Harvard Medical School, Boston, MA, USA
- 3. Shriners Hospitals for Children—Boston, Boston, MA, USA
- 4. NeuroPhage Pharmaceuticals, Inc., Cambridge, MA, USA