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Neurofilament light is a treatment‐responsive biomarker in CLN2 disease
- Source :
- Annals of Clinical and Translational Neurology, Annals of Clinical and Translational Neurology, Vol 6, Iss 12, Pp 2437-2447 (2019)
- Publication Year :
- 2019
- Publisher :
- John Wiley and Sons Inc., 2019.
-
Abstract
- Objective Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare, progressive, fatal neurodegenerative pediatric disorder resulting from deficiencies of the lysosomal enzyme tripeptidyl peptidase 1 that are caused by mutations in TPP1. Identifying biomarkers of CLN2 disease progression will be important in assessing the efficacy of therapeutic interventions for this disorder. Neurofilament light is an intrinsic component of healthy neurons; elevated circulating extracellular neurofilament light is a biomarker of neuropathology in several adult‐onset neurological diseases. Our objective was to assess whether circulating neurofilament light is a biomarker that is responsive to enzyme replacement therapy (ERT) in CLN2 disease. Methods Using an ultrasensitive immunoassay, we assessed plasma neurofilament light changes during disease progression in a canine model of CLN2 disease and in ERT clinical trial CLN2 disease patients. Results In tripeptidyl peptidase 1 (TPP1)‐null dogs (N = 11), but not in control dogs [N = 6 (TPP1 +/−) and N = 27 (WT)], neurofilament light levels increased more than tenfold above initial low baseline levels during disease progression. Before treatment in 21 human subjects with CLN2 disease (age range: 1.72–6.85 years), neurofilament light levels were 48‐fold higher (P
- Subjects :
- 0301 basic medicine
Male
Pathology
medicine.medical_specialty
Neurosciences. Biological psychiatry. Neuropsychiatry
Neuropathology
Disease
Aminopeptidases
Tripeptidyl peptidase
Animals, Genetically Modified
03 medical and health sciences
0302 clinical medicine
Dogs
Neurofilament Proteins
Neuronal Ceroid-Lipofuscinoses
Extracellular
Medicine
Animals
Humans
Enzyme Replacement Therapy
RC346-429
Child
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Research Articles
Tripeptidyl-Peptidase 1
business.industry
General Neuroscience
Infant
Enzyme replacement therapy
Pathophysiology
Recombinant Proteins
Neuronal Ceroid Lipofuscinosis Type 2
Disease Models, Animal
030104 developmental biology
Child, Preschool
Disease Progression
Biomarker (medicine)
Female
Neurology. Diseases of the nervous system
Neurology (clinical)
Serine Proteases
business
030217 neurology & neurosurgery
Biomarkers
RC321-571
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 23289503
- Volume :
- 6
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Annals of Clinical and Translational Neurology
- Accession number :
- edsair.doi.dedup.....7b1f747839ea2150bd81acb05cdddfc9