Large Animal Models for Batten Disease

Weber, Krystal L.; Pearce, David A.

doi:10.1177/0883073813493666

Cited by 22 publications

(18 citation statements)

References 33 publications

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“…In this respect, studies with animals that have larger brains (eg, sheep and dogs) will be required. 5,8 In addition to their larger and more complex brains for scaling up the delivery of therapies, the extent of pathology and its regionalised nature is more pronounced in the brains of sheep and dogs with NCLs than in corresponding mouse models (possibly because of the size difference), and pathology appears to more closely re semble that of human cases. 6,7 With the ability to engineer genetically modified pigs and sheep, such species might prove invaluable for further understanding the effects of the disease and to improve therapies.…”

Section: Pathologymentioning

confidence: 99%

“…This has necessitated a change in disease nomenclature based on the gene defect augmented with age of presentation. 4 There has been an emphasis on understanding the staging of these disorders and their molecular pathways, and advancing experimental therapies such as enzyme replacement and gene therapy in animal models, [5][6][7][8] together with the establishment of patient registries 9,10 and disease rating scales. 11,12 These efforts have culminated in the approval by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) of the first treatment for a NCL disorder: enzyme replacement therapy for neuronal ceroid lipofuscinosis type 2 (CLN2) disease.…”

Section: Introductionmentioning

confidence: 99%

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Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis

Mole

Anderson

Band³

et al. 2019

The Lancet Neurology

151

161

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Treatment of the neuronal ceroid lipofuscinoses, also known as Batten disease, is at the start of a new era because of diagnostic and therapeutic advances relevant to this group of inherited neurodegenerative and life-limiting disorders that affect children. Diagnosis has improved with the use of comprehensive DNA-based tests that simultaneously screen for many genes. The identification of disease-causing mutations in 13 genes provides a basis for understanding the molecular mechanisms underlying neuronal ceroid lipofuscinoses, and for the development of targeted therapies. These targeted therapies include enzyme replacement therapies, gene therapies targeting the brain and the eye, cell therapies, and pharmacological drugs that could modulate defective molecular pathways. Such therapeutic developments have the potential to enable earlier diagnosis and better targeted therapeutic management. The first approved treatment is an intracerebroventricularly administered enzyme for neuronal ceroid lipofuscinosis type 2 disease that delays symptom progression. Efforts are underway to make similar progress for other forms of the disorder.

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Section: Pathologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis

Mole

Anderson

Band³

et al. 2019

The Lancet Neurology

151

161

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“…Importantly, studies have shown AD-associated neurofibrillary accumulation (tau pathology) in normal aged sheep (Braak et al, 1994, Nelson andSaper 1995); a feature which is absent in wild type rodents and has made AD modelling challenging in rats and mice (Hardy and Selkoe 2002). While the rate of naturally occurring dementia in sheep is unknown (as most farmed sheep are culled before reaching old age), sheep with cognitive deficits are studied due to natural mutations in genes causing Battens Disease in humans (Cook et al, 2002, Jolly et al, 1980, Weber and Pearce 2013 Sheep are readily trainable for use in tests of cognitive function (Morton and Avanzo 2011) and sheep suffering from a progressive neurological disease can be quantified longitudinally using modern methods, such as EEG (Perentos et al, 2015) and MRI (Sawiak et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Alzheimer's disease markers in the aged sheep (Ovis aries)

Reid

Mckean

Henty

et al. 2017

Neurobiology of Aging

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This study reports the identification and characterization of markers of Alzheimer's disease (AD) in aged sheep (Ovis aries) as a preliminary step toward making a genetically modified large animal model of AD. Importantly, the sequences of key proteins involved in AD pathogenesis are highly conserved between sheep and human. The processing of the amyloid-β (Aβ) protein is conserved between sheep and human, and sheep Aβ/Aβ ratios in cerebrospinal fluid (CSF) are also very similar to human. In addition, total tau and neurofilament light levels in CSF are comparable with those found in human. The presence of neurofibrillary tangles in aged sheep brain has previously been established; here, we report for the first time that plaques, the other pathologic hallmark of AD, are also present in the aged sheep brain. In summary, the biological machinery to generate the key neuropathologic features of AD is conserved between the human and sheep, making the sheep a good candidate for future genetic manipulation to accelerate the condition for use in pathophysiological discovery and therapeutic testing.

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“…Data from the literature confirm that natural cases of NCL occur in a large variety of species including the bovine (19, 20). Research in prion pathology, the transmissible neurodegenerative conditions affecting human and a wide range of animal species, lead to an increased awareness of the need to use large animal models such as the bovine, in addition to conventional laboratory animals (21).…”

Section: Bovine Brain: a Translational Model For Altered Sexual Diffementioning

confidence: 79%

Bovine Brain: An in vitro Translational Model in Developmental Neuroscience and Neurodegenerative Research

Peruffo

Cozzi

2014

Front. Pediatr.

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Animal models provide convenient and clinically relevant tools in the research on neurodegenerative diseases. Studies on developmental disorders extensively rely on the use of laboratory rodents. The present mini-review proposes an alternative translational model based on the use of fetal bovine brain tissue. The bovine (Bos taurus) possesses a large and highly gyrencephalic brain and the long gestation period (41 weeks) is comparable to human pregnancy (38–40 weeks). Primary cultures obtained from fetal bovine brain constitute a validated in vitro model that allows examinations of neurons and/or glial cells under controlled and reproducible conditions. Physiological processes can be also studied on cultured bovine neural cells incubated with specific substrates or by electrically coupled electrolyte-oxide-semiconductor capacitors that permit direct recording from neuronal cells. Bovine neural cells and specific in vitro cell culture could be an alternative in comparative neuroscience and in neurodegenerative research, useful for studying development of normal and altered circuitry in a long gestation mammalian species. Use of bovine tissues would promote a substantial reduction in the use of laboratory animals.

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Large Animal Models for Batten Disease

Cited by 22 publications

References 33 publications

Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis

Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis

Alzheimer's disease markers in the aged sheep (Ovis aries)

Bovine Brain: An in vitro Translational Model in Developmental Neuroscience and Neurodegenerative Research

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