Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2
The introduction of intracerebroventricular (ICV) enzyme replacement therapy (ERT) for treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease has produced dramatic improvements in disease management. However, assessments of therapeutic effect for ICV ERT are limited to clinical observatio...
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MDPI AG
2023-01-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/2/209 |
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| author | Siyamini Sivananthan Laura Lee Glenn Anderson Barbara Csanyi Ruth Williams Paul Gissen |
| author_facet | Siyamini Sivananthan Laura Lee Glenn Anderson Barbara Csanyi Ruth Williams Paul Gissen |
| author_sort | Siyamini Sivananthan |
| collection | DOAJ |
| description | The introduction of intracerebroventricular (ICV) enzyme replacement therapy (ERT) for treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease has produced dramatic improvements in disease management. However, assessments of therapeutic effect for ICV ERT are limited to clinical observational measures, namely the CLN2 Clinical Rating Scale, a subjective measure of motor and language performance. There is a need for an objective biomarker to enable assessments of disease progression and response to treatment. To address this, we investigated whether the proportion of cells with abnormal storage inclusions on electron microscopic examination of peripheral blood buffy coats could act as a biomarker of disease activity in CLN2 disease. We conducted a prospective longitudinal analysis of six patients receiving ICV ERT. We demonstrated a substantial and continuing reduction in the proportion of abnormal cells over the course of treatment, whereas symptomatic scores revealed little or no change over time. Here, we proposed the use of the proportion of cells with abnormal storage as a biomarker of response to therapy in CLN2. In the future, as more tissue-specific biomarkers are developed, the buffy coats may form part of a panel of biomarkers in order to give a more holistic view of a complex disease. |
| first_indexed | 2024-03-11T09:04:57Z |
| format | Article |
| id | doaj.art-5b154f3e969844f7bdbfd1866119a97e |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T09:04:57Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | Brain Sciences |
| spelling | doaj.art-5b154f3e969844f7bdbfd1866119a97e2023-11-16T19:27:45ZengMDPI AGBrain Sciences2076-34252023-01-0113220910.3390/brainsci13020209Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2Siyamini Sivananthan0Laura Lee1Glenn Anderson2Barbara Csanyi3Ruth Williams4Paul Gissen5Department of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UKDepartment of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UKDepartment of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UKDepartment of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UKDepartment of Children’s Neurosciences, Evelina London Children’s Hospital, London SE1 7EH, UKDepartment of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UKThe introduction of intracerebroventricular (ICV) enzyme replacement therapy (ERT) for treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease has produced dramatic improvements in disease management. However, assessments of therapeutic effect for ICV ERT are limited to clinical observational measures, namely the CLN2 Clinical Rating Scale, a subjective measure of motor and language performance. There is a need for an objective biomarker to enable assessments of disease progression and response to treatment. To address this, we investigated whether the proportion of cells with abnormal storage inclusions on electron microscopic examination of peripheral blood buffy coats could act as a biomarker of disease activity in CLN2 disease. We conducted a prospective longitudinal analysis of six patients receiving ICV ERT. We demonstrated a substantial and continuing reduction in the proportion of abnormal cells over the course of treatment, whereas symptomatic scores revealed little or no change over time. Here, we proposed the use of the proportion of cells with abnormal storage as a biomarker of response to therapy in CLN2. In the future, as more tissue-specific biomarkers are developed, the buffy coats may form part of a panel of biomarkers in order to give a more holistic view of a complex disease.https://www.mdpi.com/2076-3425/13/2/209neuronal ceroid lipofuscinosis type 2 (CLN2) diseaselysosomal storage disorderintracerebroventricularenzyme replacement therapydisease progressionneurodegeneration |
| spellingShingle | Siyamini Sivananthan Laura Lee Glenn Anderson Barbara Csanyi Ruth Williams Paul Gissen Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2 Brain Sciences neuronal ceroid lipofuscinosis type 2 (CLN2) disease lysosomal storage disorder intracerebroventricular enzyme replacement therapy disease progression neurodegeneration |
| title | Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2 |
| title_full | Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2 |
| title_fullStr | Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2 |
| title_full_unstemmed | Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2 |
| title_short | Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2 |
| title_sort | buffy coat score as a biomarker of treatment response in neuronal ceroid lipofuscinosis type 2 |
| topic | neuronal ceroid lipofuscinosis type 2 (CLN2) disease lysosomal storage disorder intracerebroventricular enzyme replacement therapy disease progression neurodegeneration |
| url | https://www.mdpi.com/2076-3425/13/2/209 |
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