Cerebrospinal fluid neurofilament light levels in CLN2 disease patients treated with enzyme replacement therapy normalise after two years on treatment

التفاصيل البيبلوغرافية
العنوان: Cerebrospinal fluid neurofilament light levels in CLN2 disease patients treated with enzyme replacement therapy normalise after two years on treatment
المؤلفون: Sara E. Mole, Henrik Zetterberg, Katharina Iwan, Laura M. Lee, Nina Patel, Mina Borisova, Paul Gissen, Amanda Heslegrave, Wendy E. Heywood, Philippa B. Mills, Kevin Mills, Rebecca Bower
المصدر: F1000Research. 10:614
بيانات النشر: F1000 Research Ltd, 2021.
سنة النشر: 2021
مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, General Immunology and Microbiology, business.industry, Neurodegeneration, General Medicine, Enzyme replacement therapy, Cerliponase alfa, Disease, medicine.disease, Gastroenterology, General Biochemistry, Genetics and Molecular Biology, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Cerebrospinal fluid, Internal medicine, Biomarker (medicine), Medicine, Neuronal ceroid lipofuscinosis, General Pharmacology, Toxicology and Pharmaceutics, business, 030217 neurology & neurosurgery
الوصف: Classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is caused by a deficiency of tripeptidyl-peptidase-1. In 2017, the first CLN2 enzyme replacement therapy (ERT) cerliponase alfa (Brineura) was approved by the FDA and EMA. The CLN2 disease clinical rating scale (CLN2 CRS) was developed to monitor loss of motor function, language and vision as well as frequency of generalised tonic clonic seizures. Using CLN2 CRS in an open label clinical trial it was shown that Brineura slowed down the progression of CLN2 symptoms. Neurofilament light chain (NfL) is a protein highly expressed in myelinated axons. An increase of cerebrospinal fluid (CSF) and blood NfL is found in a variety of neuroinflammatory, neurodegenerative, traumatic, and cerebrovascular diseases. We analysed CSF NfL in CLN2 patients treated with Brineura to establish whether it can be used as a possible biomarker of response to therapy. Newly diagnosed patients had CSF samples collected and analysed at first treatment dose and up to 12 weeks post-treatment to look at acute changes. Patients on a compassionate use programme who were already receiving ERT for approximately 1yr had CSF samples collected and NfL analysed over the following 1.3 years (2.3 years post-initiation of ERT) to look at long-term changes. All newly diagnosed patients we investigated with classical late infantile phenotype had high NfL levels >2000 pg/ml at start of treatment. No significant change was observed in NfL up to 12 weeks post-treatment. After one year of ERT, two out of six patients still had high NfL levels, but all patients showed a continued decrease, and all had low NfL levels after two years on ERT. NfL levels appear to correspond and predict improved clinical status of patients on ERT and could be useful as a biomarker to monitor neurodegeneration and verify disease modification in CLN2 patients on ERT.
تدمد: 2046-1402
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::2bb564316030f63398369a48f862c8eaTest
https://doi.org/10.12688/f1000research.54556.1Test
حقوق: OPEN
رقم الانضمام: edsair.doi...........2bb564316030f63398369a48f862c8ea
قاعدة البيانات: OpenAIRE