A5020039383- Lysosomal Storage Disorders Research
- Virus-based gene therapy research
- Vector-Borne Animal Diseases
- Cellular transport and secretion
- Retinal Development and Disorders
- Cytomegalovirus and herpesvirus research
- Neurological diseases and metabolism
- RNA regulation and disease
- Calcium signaling and nucleotide metabolism
- Galectins and Cancer Biology
- Hereditary Neurological Disorders
- Animal Genetics and Reproduction
- Retinal Diseases and Treatments
- T-cell and Retrovirus Studies
- Advanced MRI Techniques and Applications
- Neurogenesis and neuroplasticity mechanisms
- Trypanosoma species research and implications
- Herpesvirus Infections and Treatments
- Neonatal and fetal brain pathology
- Autophagy in Disease and Therapy
- Animal Disease Management and Epidemiology
- Viral Infectious Diseases and Gene Expression in Insects
- Sleep and Wakefulness Research
- Signaling Pathways in Disease
- Prion Diseases and Protein Misfolding
Lincoln University
2015-2025
University of Otago
2018-2025
Lincoln University - Pennsylvania
2021-2022
Mitchell College
2021
Research Network (United States)
2015
Creating valid mouse models of slowly progressing human neurological diseases is challenging, not least because the short lifespan rodents confounds realistic modelling disease time course. With their large brains and long lives, sheep offer significant advantages for translational studies disease. Here we used normal CLN5 Batten affected to demonstrate use species studying function in a model We show that electroencephalography can be sheep, longitudinal recordings spanning many months are...
ABSTRACT Purpose Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of rare inherited neurodegenerative disorders caused by mutations in one 13 lipofuscinosis neuronal ( CLN ) genes. The diseases share common set symptoms, including motor and cognitive dysfunction, progressive loss vision, seizure activity. A naturally occurring model CLN5 NCL exists New Zealand Borderdale sheep, which exhibit similar clinical disease post‐mortem pathology to the human disease. Recent trials...
The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are inherited neurodegenerative lysosomal storage diseases with common clinical features of blindness and seizures culminating in premature death. Gene-therapy strategies for these depend on whether the missing activity is a secreted protein taken up by neighboring cells, or an intramembrane that requires careful targeting. Therapies best developed animal models large complex human-like brains. Lentiviral-mediated gene delivery to...
Sheep have large brains with human-like anatomy, making them a useful species for studying brain function. Sleep homeostasis has not been studied in sheep. Here, we establish correlates of sleep sheep through deprivation experiment. We then use these to elucidate the nature deficits naturally occurring ovine model neuronal ceroid lipofuscinosis (NCL, Batten disease) caused by mutation <i>CLN5</i>. In humans, mutations this gene lead cortical atrophy and blindness, as well abnormalities....
Abstract Aims Synapses represent a major pathological target across broad range of neurodegenerative conditions. Recent studies addressing molecular mechanisms regulating synaptic vulnerability and degeneration have relied heavily on invertebrate mouse models. Whether similar neuropathological changes underpin breakdown in large animal models human patients with disease remains unclear. We therefore investigated whether regulators pathophysiology, previously identified Drosophila models, are...
Abstract Introduction The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are a group of fatal neurodegenerative lysosomal storage diseases children caused by various mutations in range genes. Forms associated with two these, CLN5 and CLN6, being investigated well‐established sheep models. Brain atrophy leading to psychomotor degeneration is among the defining features, as regional progressive ossification inner cranium. Ongoing viral‐mediated gene therapy trials these yielding...
Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It recessive genetic lysosomal storage characterised progressive neurodegeneration. starts insidiously and leads to blindness, epilepsy dementia affected children. Sheep that are homozygous for natural mutation CLN6 have an ovine form of Here, we used vivo magnetic resonance imaging track brain changes 4 unaffected carriers 6 sheep. We scanned each sheep times, between 17 22 months age....
Abstract Sheep with naturally occurring CLN5 and CLN6 forms of neuronal ceroid lipofuscinoses (Batten disease) share the key clinical features human disease represent an ideal model system in which efficacy gene therapies is developed test. However, it was first important to characterize neuropathological changes that occur progression affected sheep. This study compared neurodegeneration, neuroinflammation, lysosomal storage accumulation Borderdale, South Hampshire, Merino sheep brains from...
CLN5 neuronal ceroid lipofuscinosis (NCL, Batten disease) is a rare, inherited fatal neurodegenerative disorder caused by mutations in the gene. The disease characterised progressive loss, blindness, and premature death. There no cure. This study evaluated efficacy of intracerebroventricular (ICV) delivery an adeno-associated viral vector encoding ovine (scAAV9/oCLN5) naturally occurring sheep model disease. affected (CLN5-/-) received low, moderate, or high doses scAAV9/oCLN5 at three...
This article presents datasets associated with the research entitled "Intravitreal gene therapy protects against retinal dysfunction and degeneration in sheep CLN5 Batten disease" (Murray et al., [1]). The neuronal ceroid lipofuscinoses (NCL; disease) are a group of fatal inherited diseases caused by mutations number CLN genes that lead to degenerative encephalopathies children. Naturally-occuring models NCL exist. Affected share clinical pathological features human disease, including...
Abstract Background Mucopolysaccharidosis IIIC (MPSIIIC) is one of four Sanfilippo diseases sharing clinical symptoms severe cognitive decline and shortened lifespan. The missing enzyme, heparan sulfate acetyl-CoA: α-glucosaminide-N-acetyltransferase (HGSNAT), bound to the lysosomal membrane, therefore cannot cross blood-brain barrier or diffuse between cells. We previously demonstrated disease correction in MPSIIIC mice using an Adeno-Associated Vector (AAV) delivering HGSNAT via...
Mutations in the CLN5 gene cause fatal, pediatric, neurodegenerative disease neuronal ceroid lipofuscinosis. Affected children suffer progressive loss, visual failure and premature death. Presently there is no treatment. This study evaluated dual intracerebroventricular (ICV) intravitreal (IVT) administration of a self-complementary adeno-associated viral vector encoding ovine (scAAV9/oCLN5) into affected sheep (CLN5 −/− ) at various stages. progression was slowed pre-symptomatic who...
Abstract Objectives To determine the prevalence of retinal lesions and describe fundoscopic findings retinopathy in Greyhound dogs Manawatu/Whanganui region New Zealand. examine possible associations between sex, age, racing variables with study population. histologic seven Greyhounds Methods Two hundred from Zealand underwent fundoscopy fundic photography to identify score degree retinopathy. Associations as well variables, were examined. Histologic examination retina was undertaken on eyes...