Volumetric Description of Brain Atrophy in Neuronal Ceroid Lipofuscinosis 2: Supratentorial Gray Matter Shows Uniform Disease Progression

Löbel, Ulrike; Sedlacik, Jan; Nickel, Miriam; Lezius, Susanne; Fiehler, Jens; Nestrašil, Igor; Kohlschütter, Alfried; Schulz, Angela

doi:10.3174/ajnr.a4816

Cited by 20 publications

(22 citation statements)

References 20 publications

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“…Grey matter volumes of treated patients decreased by 6.7% on average; however, volumetric changes were not recorded for historical controls. Nevertheless, this value is much lower than that reported from separate studies, which indicate an average loss of cortical volume of ~15–20% annually for patients with untreated CLN2 Batten disease 138 .…”

Section: Advances In Therapy Developmentcontrasting

confidence: 55%

Therapeutic landscape for Batten disease: current treatments and future prospects

et al. 2019

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Batten disease (also known as neuronal ceroid lipofuscinoses) constitutes a family of devastating lysosomal storage disorders that collectively represent the most common inherited paediatric neurodegenerative disorders worldwide. Batten disease can result from mutations in 1 of 13 genes. These mutations lead to a group of diseases with loosely overlapping symptoms and pathology. Phenotypically, patients with Batten disease have visual impairment and blindness, cognitive and motor decline, seizures and premature death. Pathologically, Batten disease is characterized by lysosomal accumulation of autofluorescent storage material, glial reactivity and neuronal loss. Substantial progress has been made towards the development of effective therapies and treatments for the multiple forms of Batten disease. In 2017, cerliponase alfa (Brineura), a tripeptidyl peptidase enzyme replacement therapy, became the first globally approved treatment for CLN2 Batten disease. Here, we provide an overview of the promising therapeutic avenues for Batten disease, highlighting current FDA-approved clinical trials and prospective future treatments.

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Section: Advances In Therapy Developmentcontrasting

confidence: 55%

Therapeutic landscape for Batten disease: current treatments and future prospects

et al. 2019

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“…28 Although MRI is not sensitive or specific f or early diagnosis, it is an excellent tool to objectively monitor the progression of brain changes, particularly with ad vances in resolution and processing, and neuro imaging techniques such as diffusion tensor imaging allow assess ment of disorganisation of white matter tracts and atrophy. Two prospective studies 28,29 in patients with CLN2 disease have shown that the loss of cortical grey matter volume with increasing age might be a sensitive biomarker to monitor disease progression.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…2,40 Atrophy of the cerebellum is variable but evident in the later stages of all NCLs. 28,29,43 Neuronal depletion in the retina commences in the photoreceptor outer segments, proceeding to the inner segments, nerve cell bodies, and ganglionic layer, and occurs early in CLN3 disease, 44,45 while other symptoms (eg, epilepsy) precede visual loss in other types of NCLs. 1,40 In all forms of NCLs lipopigment storage material accumulates in macro phages, neurons, and some somatic tissues, including vascular endothelial and smooth muscle cells.…”

Section: Pathologymentioning

confidence: 99%

Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis

Mole

Anderson

Band³

et al. 2019

The Lancet Neurology

143

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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“…All gray regions of the brain are affected by neuronal death, showing however differential patterns in the topography of neuronal loss, the rate of progression and the secondary involvement of the white matter. Selective neurodegeneration, targeting specific regions and particular cell populations, can be observed during the early stages of the disease, and the patterns of disease evolution can be monitored by neuroimaging studies (136)(137)(138)(139)(140). Whether these features reflect the genetic heterogeneity of the NCL is a matter to be investigated further.…”

Section: Pathology and Pathogenetic Mechanismsmentioning

confidence: 99%

Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview

Simonati

Williams

2022

Front. Neurol.

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The main aim of this review is to summarize the current state-of-art in the field of childhood Neuronal Ceroid Lipofuscinosis (NCL), a group of rare neurodegenerative disorders. These are genetic diseases associated with the formation of toxic endo-lysosomal storage. Following a brief historical review of the evolution of NCL definition, a clinically-oriented approach is used describing how the early symptoms and signs affecting motor, visual, cognitive domains, and including seizures, may lead clinicians to a rapid molecular diagnosis, avoiding the long diagnostic odyssey commonly observed. We go on to focus on recent advances in NCL research and summarize contributions to knowledge of the pathogenic mechanisms underlying NCL. We describe the large variety of experimental models which have aided this research, as well as the most recent technological developments which have shed light on the main mechanisms involved in the cellular pathology, such as apoptosis and autophagy. The search for innovative therapies is described. Translation of experimental data into therapeutic approaches is being established for several of the NCLs, and one drug is now commercially available. Lastly, we show the importance of palliative care and symptomatic treatments which are still the main therapeutic interventions.

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Volumetric Description of Brain Atrophy in Neuronal Ceroid Lipofuscinosis 2: Supratentorial Gray Matter Shows Uniform Disease Progression

Cited by 20 publications

References 20 publications

Therapeutic landscape for Batten disease: current treatments and future prospects

Therapeutic landscape for Batten disease: current treatments and future prospects

Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis

Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview

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