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dc.contributor.authorFlor, Raul de la
dc.contributor.authorRobertson, Janette
dc.contributor.authorShevchenko, Rostislav V.
dc.contributor.authorAlavijeh, Mo
dc.contributor.authorBickerton, Sean
dc.contributor.authorFahmy, Tarek
dc.contributor.authorMetcalfe, Su M.
dc.date.accessioned2021-04-21T05:13:31Z
dc.date.available2021-04-21T05:13:31Z
dc.date.issued2021-04-07
dc.date.submitted2020-12-11
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/321372
dc.description.abstractMultiple sclerosis (MS) is a demyelinating autoimmune disease that attacks the brain, with year-on-year loss of brain volume, starting late teens and becoming manifest late twenties. There is no cure, and current therapies are immunosuppressive only. LIF is a vital stem cell growth factor active throughout life—and essential for health of the central nervous system (CNS), being tolerogenic, myelinogenic, and neuroprotective. Nano-formulation of LIF (LIFNano) using FDA-approved PLGA captures LIF's compound therapeutic properties, increasing potency 1,000-fold when targeted to CD4 (LIFNano-CD4). Moreover, circulating CD4+ lymphocytes are themselves regulated by LIF to express the Treg phenotype, known to release T cell-derived LIF upon engagement with cognate antigen, perpetuating antigen-specific self-tolerance. With the longer-term aim of treating inflammatory lesions of MS, we asked, does LIFNano-CD4 cross the blood–brain barrier (BBB)? We measure pK and pD using novel methodologies, demonstrate crossing of the BBB, show LIF-cargo-specific anti-inflammatory efficacy in the frontal cortex of the brain, and show safety of intravenous delivery of LIFNano-CD4 at doses known to provide efficacious concentrations of LIF cargo behind the BBB.
dc.languageen
dc.publisherFrontiers Media S.A.
dc.subjectMedical Technology
dc.subjectLIF
dc.subjectBBB
dc.subjectCD4+ T lymphocyte
dc.subjectPLGA nanoparticles
dc.subjectpK/pD
dc.subjectEAE
dc.subjectmultiple sclerosis
dc.titleMultiple Sclerosis: LIFNano-CD4 for Trojan Horse Delivery of the Neuro-Protective Biologic “LIF” Into the Brain: Preclinical Proof of Concept
dc.typeOther
dc.date.updated2021-04-21T05:13:31Z
prism.publicationNameFrontiers in Medical Technology
prism.volume3
dc.identifier.doi10.17863/CAM.68493
dcterms.dateAccepted2021-01-26
rioxxterms.versionofrecord10.3389/fmedt.2021.640569
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn2673-3129


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