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dc.contributor.authorKay, Graham W.en
dc.contributor.authorPalmer, David N.en
dc.description.abstractBackground: The neuronal ceroid lipofuscinoses (NCLs; or Batten disease) are fatal inherited human neurodegenerative diseases affecting an estimated 1:12,500 live births worldwide. They are caused by mutations in at least 11 different genes. Currently, there are no effective treatments. Progress into understanding pathogenesis and possible therapies depends on studying animal models. The most studied animals are the CLN6 South Hampshire sheep, in which the course of neuropathology closely follows that in affected children. Neurodegeneration, a hallmark of the disease, has been linked to neuroinflammation and is consequent to it. Activation of astrocytes and microglia begins prenatally, starting from specific foci associated with the later development of progressive cortical atrophy and the development of clinical symptoms, including the occipital cortex and blindness. Both neurodegeneration and neuroinflammation generalize and become more severe with increasing age and increasing clinical severity. The purpose of this study was to determine if chronic administration of an anti-inflammatory drug, minocycline, from an early age would halt or reverse the development of disease. Method: Minocycline, a tetracycline family antibiotic with activity against neuroinflammation, was tested by chronic oral administration of 25 mg minocycline/kg/day to presymptomatic lambs affected with CLN6 NCL at 3 months of age to 14 months of age, when clinical symptoms are obvious, to determine if this would suppress neuroinflammation or disease progression. Results: Minocycline was absorbed without significant rumen biotransformation to maintain pharmacological concentrations of 1 μM in plasma and 400 nM in cerebrospinal fluid, but these did not result in inhibition of microglial activation or astrocytosis and did not change the neuronal loss or clinical course of the disease. Conclusion: Oral administration is an effective route for drug delivery to the central nervous system in large animals, and model studies in these animals should precede highly speculative procedures in humans. Minocycline does not inhibit a critical step in the neuroinflammatory cascade in this form of Batten disease. Identification of the critical steps in the neuroinflammatory cascade in neurodegenerative diseases, and targeting of specific drugs to them, will greatly increase the likelihood of success.en
dc.publisherBioMed Centralen
dc.relationThe original publication is available from - BioMed Central -
dc.rights© 2013 Kay and Palmer; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectAnti-inflammatory drugsen
dc.subjectBatten diseaseen
dc.subjectCerebrospinal fluiden
dc.subjectCortical atrophyen
dc.subjectOvine modelen
dc.subjectNeurology & Neurosurgeryen
dc.subject.meshNeurodegenerative Diseasesen
dc.subject.meshDisease Progressionen
dc.subject.meshGlial Fibrillary Acidic Proteinen
dc.subject.meshAnti-Bacterial Agentsen
dc.subject.meshLiver Function Testsen
dc.subject.meshChromatography, High Pressure Liquiden
dc.subject.meshMacrophage Activationen
dc.subject.meshImage Processing, Computer-Assisteden
dc.subject.meshNeuronal Ceroid-Lipofuscinosesen
dc.titleChronic oral administration of minocycline to sheep with ovine CLN6 neuronal ceroid lipofuscinosis maintains pharmacological concentrations in the brain but does not suppress neuroinflammation or disease progressionen
dc.typeJournal Article
lu.contributor.unitLincoln Universityen
lu.contributor.unitFaculty of Agriculture and Life Sciencesen
lu.contributor.unitDepartment of Wine, Food and Molecular Biosciencesen
lu.contributor.unitResearch Management Officeen
lu.contributor.unit/LU/Research Management Office/2018 PBRF Staff groupen
dc.subject.anzsrc1103 Clinical Sciencesen
dc.subject.anzsrc1109 Neurosciencesen
dc.subject.anzsrc1107 Immunologyen
dc.relation.isPartOfJournal of Neuroinflammationen
pubs.organisational-group/LU/Agriculture and Life Sciences
pubs.organisational-group/LU/Agriculture and Life Sciences/WFMB
pubs.organisational-group/LU/Research Management Office
pubs.organisational-group/LU/Research Management Office/2018 PBRF Staff group

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