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Enzyme replacement therapy for CLN2 disease: MRI volumetry shows significantly slower volume loss compared to a natural history cohort.
Gaur, Pritika; Gissen, Paul; Biswas, Asthik; Mankad, Kshitij; Sudhakar, Sniya; D'Arco, Felice; Schulz, Angela; Fiehler, Jens; Sedlacik, Jan; Löbel, Ulrike.
Affiliation
  • Gaur P; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
  • Gissen P; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
  • Biswas A; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
  • Mankad K; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
  • Sudhakar S; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
  • D'Arco F; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
  • Schulz A; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
  • Fiehler J; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
  • Sedlacik J; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
  • Löbel U; From the Department of Radiology, Great Ormond Street Hospital, London, UK (PG, AB, KM, SS, FD, UL), National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK (PG), Department of Paediatrics, University Medical Center Hambur
AJNR Am J Neuroradiol ; 2024 Jul 08.
Article in En | MEDLINE | ID: mdl-38977290
ABSTRACT
BACKGROUND AND

PURPOSE:

Neuronal ceroid lipofuscinoses (NCL) are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for CLN2, a subtype of NCL. The aim of this study was to quantify brain volume loss in CLN2 disease of patients on ERT in comparison to a natural history cohort using magnetic resonance imaging (MRI). MATERIALS AND

METHODS:

Nineteen (13 female, 6 male) patients with CLN2 disease at one UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1 to 9 years). Brain segmentation was done using FreeSurfer. Volume measurements for supratentorial grey and white matter, deep grey matter (basal ganglia/thalami), lateral ventricles, and cerebellar grey and white matter were recorded. The volume change over time was analyzed using a linear mixed-effects model excluding scans before treatment start. Comparison was made to a published natural history cohort of 12 patients (8 female, 4 male) which was reanalyzed using the same method.

RESULTS:

Brain volume loss of all segmented brain regions was much slower in treated patients compared to the natural history cohort. For example, supratentorial grey matter volume in treated patients decreased by 3±0.74% (p<0.001) annually compared to an annual volume loss of 16.8±1.5% (p<0.001) in the natural history cohort.

CONCLUSIONS:

Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared to a natural history cohort in several anatomical regions. Our results complement prior clinical data which found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease. ABBREVIATIONS NCL = Neuronal Ceroid Lipofuscinosis, CLN2 = Neuronal Ceroid Lipofuscinosis type 2, TPP1 = tripeptidyl peptidase 1, ERT = enzyme replacement therapy, EMA = European Medicines Agency, ICV = intra-cerebro-ventricular reservoir.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: AJNR Am J Neuroradiol Year: 2024 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: AJNR Am J Neuroradiol Year: 2024 Document type: Article