More than 1,100 people with amyotrophic lateral sclerosis (ALS) are currently participating in the study "NF-L in ALS", which is made possible by the Boris Canessa ALS Foundation (https://canessa-als-stiftung.org/projekte/nf-l-studie/). Within the study, the concentration of the biomarker "neurofilament light chain" (NF-L) is determined in the blood at 6-month intervals. The results of the NF-L analysis are reported during the visits to the study centres.

A new chart in the ALS app and on the APST web portal enables faster reporting of NF-L-analysis results and an overview of one's own NF-L analysis results during the progression of the disease.

Who can use the new function?

The new function can be used by patients who participate in the NF-L-ALS study and the APST care network. Parallel participation in the APST network is necessary for the notification of results, as the ALS app is not a formal component of the "NF-L in ALS" study.

For reasons of data protection, it is necessary that the NF-L study results can only be displayed on the APST web portal (or in the ALS app) if a registration to and corresponding declaration of consent for the use of the APST network are given. For the optional display of the NF-L analysis results in the APST web portal (or in the ALS app), there has been a positive decision by the ethics committee of the Charité of 22 June 2021.

How are the NF-L analysis results displayed?

The NF analysis results are displayed in a diagram on the APST web portal and within the ALS app. This means that users now have two charts displaying the progression of ALS at their disposal: the NF-L chart and the ALS-FRS chart. In the APST web portal, the NF-L diagram can be found under the "Scales" tab. Within the ALS app, the NF-L diagram is located on the "Progression of ALS" page - under the ALS-FRS history diagram.

Figure: The NF-L diagram as displayed within the APST web portal. The normal range of NF-L serum concentrations is shown in colour (light blue). The steps in the diagram result from a natural increase in NF-L serum concentrations with age.

NF-L can also be detected at lower concentrations in healthy people. However, in the course of life - even in healthy people - the NF-L level increases. The normal range of NF-L serum concentrations is shown in colour (light blue). The natural increase can be seen in the diagram, as every ten years the normal range of NF-L serum concentrations increases ("step" in the diagram).

The NF-L value is considered pathological as soon as the analysis result has exceeded the age-dependent threshold ("150 percentile"). In this case, the analysis result is indicated with the symbol "+++". The level of the NF-L serum concentration (given in picograms per millilitre, pg/mL) can be seen from the left-hand scale (y-axis) of the diagram.

Figure: NF-L diagram in the ALS app. An increased (pathological) NF-L serum concentration is indicated with the symbol "+++". The level of the NF-L serum concentration (in picograms per millilitre, pg/mL) can be seen from the left-hand scale.

When are the NF-L analysis results available?

The NF-L analysis does not take place immediately as it would in a "regular laboratory", but within the framework of a scientific project. For this purpose, samples from different ALS centres are pooled and analysed in batches, thus any given individual sampley is analysed with a certain delay only. Pooling of the blood samples is necessary in order to make the personnel and time effort effective. After completion of the analysis and data processing, the data for patients who participate in the APST network is transferred to the individual APST account and displayed in the web portal and within the ALS app.

What should be taken into account when being informed of the NF-L analysis results?

For patients participating in the ALS-NF-L study, due to unanswered scientific questions an expert medical interpretation of the findings is indispensable of the findings is indispensable. Various medical factors have to be taken into account. For example, the development of motor deficits is determined on the basis of the neurological examination findings and the ALS Functional Rating Scale (ALS-FRS). Further progression criteria are body weight (body mass index, BMI), respiratory capacity (slow vital capacity, SVC) and peak cough flow (PCF). Interpretation of NF-L results requires consideration, interpretation and weighing of individual factors and their combination. The interpretation of the NF-L value thus takes place within a personal doctor-patient consultations at a NF-L study centre.

Contact

Our experts will be happy to answer yourquestions about the new NF-L diagram in the ALS app and in the APST web portal.

For questions regarding**NF-L values in the APST register study: ** Dr. Dr. Susanne Spittel, s.spittel@ambulanzpartner.de
For questions regarding technology and use of the NF-L chart:    info@ambulanzpartner.de

Questions regarding the interpretation of the NF-L values should be clarified in direct doctor-patient consultations at a participating ALS centre.

On “neurofilament light chain" (NF-L)

NF-L is a nerve cell-specific protein that is released into the blood when the nerve cell is damaged. More than 80 % of ALS patients show an increase in the blood serum concentration of NF-L. The increase can in particular be observed in patients who show a clear involvement of the first motor neuron or an intermediate or higher rate of progression of the disease. Increased NF-L levels can also be observed in connection with numerous other neurological diseases (dementia, multiple sclerosis, Parkinson's disease, etc.), but can also be due to the regular ageing process. However, in patients with ALS - compared to many other neurological diseases - the increase of the NF-L concentration in the serum is more pronounced.

ALS-NF-L study

Numerous research questions regarding NF-L in the context of ALS are still unanswered. The correlation of NF-L blood serum concentration with the progression of the disease, the speed of progression and specific forms of ALS progression has not yet been adequately investigated. Another central research question is the suitability of NF-L for assessing the therapeutic efficacy of drugs and other treatment procedures in the sense of a therapeutic marker. In the ALS centre of the Charité and 12 other ALS centres, an NL-F study has been conducted since June 2020 to answer these open research questions (https://www.als-charite.de/aktuelle-studien/).

APST register study

The APST register study is an observational study in which, independent of the NFL study, treatment data of ALS care are systematically captured and analysed (ventilation therapy, nutrition therapy and provision of aids). A combined scientific evaluation of the NF-L analysis values with the treatment data is of particular interest. To participate in the registry study, it is necessary to take note of the study information and to sign two documents (declaration of consent to the registry study and to the use of data collected on the APST portal). Registration can be done via the APST web portal as well as by contacting any ALS study centre.

About Boris Canessa ALS Foundation

The "ALS-NF-L" study is made possible by a significant donation from the Boris Canessa ALS Foundation (https://canessa-als-stiftung.org/projekte/nf-l-studie/). The funding covers the purchase and operation of the SIMOA analyser (HD-X, Quanterix), the procurement of the NF-L test kits, the staffing of the analysis team as well as the project management and a project grant for several ALS centres in Germany. The funding covers a project period of three years, during which the study inclusion of 1,500 patients and the performance of 9,000 NF-L analyses will be made possible. The integration of the NF-L analysis results is supported by a project grant from the foundation for "Digital Medicine" (https://canessa-als-stiftung.org/projekte/digitale-medizin/).