Evidence map›Paper›PMID 35106137›Full record

ArticleF1000Research2021

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

Katharina Iwan, Nina Patel, Amanda Heslegrave, Mina Borisova, Laura Lee, Rebecca Bower, Sara E Mole, Philippa B Mills, Henrik Zetterberg, Kevin Mills and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in F1000Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Molecular syndromology · 2023
    Article
  5. Article
  6. Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Katharina IwanUCL Institute of Child Health, University College London, London, WC1N 1EH, UK.ORCID 0000-0002-5223-0620
Nina PatelUCL Institute of Child Health, University College London, London, WC1N 1EH, UK.
Amanda HeslegraveUK Dementia Research Institute, University College London, London, WC1E 6BT, UK.ORCID 0000-0002-7290-6405
Mina BorisovaUK Dementia Research Institute, University College London, London, WC1E 6BT, UK.
Laura LeeGreat Ormond Street Children's Hospital NHS Foundation Trust, London, WC1N 3JH, UK.
Rebecca BowerGreat Ormond Street Children's Hospital NHS Foundation Trust, London, WC1N 3JH, UK.
Sara E MoleUCL Institute of Child Health, University College London, London, WC1N 1EH, UK.ORCID 0000-0003-4385-4957
Philippa B MillsUCL Institute of Child Health, University College London, London, WC1N 1EH, UK.
Henrik ZetterbergUK Dementia Research Institute, University College London, London, WC1E 6BT, UK.
Kevin MillsUCL Institute of Child Health, University College London, London, WC1N 1EH, UK.ORCID 0000-0003-0763-8288
Paul GissenUCL Institute of Child Health, University College London, London, WC1N 1EH, UK.
Wendy E HeywoodUCL Institute of Child Health, University College London, London, WC1N 1EH, UK.ORCID 0000-0003-2106-8760
Great Ormond Street Hospital · GBUK Dementia Research Institute · GBGreat Ormond Street Hospital for Children NHS Foundation Trust · GBUniversity College London · GB

Funding

Medical Research Council MR/R025134/1Wellcome Trust
6 · The paper itself

Abstract

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.

Indexed as

Enzyme Replacement TherapyNeuronal Ceroid-LipofuscinosesBiomarkersHumansIntermediate FilamentsTripeptidyl-Peptidase 1BiomarkersTripeptidyl-Peptidase 1Enzyme replacement therapyNeurofilament lightNeuronal Ceroid lipofuscinosis

Identifiers

PMID35106137
PMCPMC8777495
OpenAlexW3186376065

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.