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Page last updated: 12th March 2024

When regulatory authorities are considering whether to recommend a drug for licencing or national funding, they assess the cost effectiveness of a drug.

This includes using information about its clinical effectiveness. The following tools and measures may be part of this:

Measures are often in the form of a scale which captures some ‘functional measure’ of a person’s abilities.

Which ones are used depend to some extent on age but also on what will provide useful information. Many focus on ‘motor performance’ and it’s recognised that they only capture what this is like on the actual day of assessment – people can have ‘off’ days or really great days. As not all scales measure the same thing, more than one may be used so that information that as wide a range of information about what change is important is captured.

Scales used include:

Some scales record patient reported outcome measures (see the tab below), such as:

  • The Egan Klassifikation 2 scale (EK2)

Some give information on fatigue such as:

  • The 6MWT (6-minute walk test) – but aren’t useful for many who have SMA.

The importance of the perspective and observations of people living with a condition, the impact it has on them and how any treatment may change this is increasingly recognised as vital.

PROMs are usually captured in short online questionnaires such as:

  • The Egan Klassifikation 2 scale (EK2)

In the UK, the SMA Patient Registry collects this information for anyone living with SMA. Their video explains more.

Biomarkers are medical indicators that can be measured to inform us of the progress of a disease.

For example, the amount of a particular protein found in a blood or urine sample may have a strong correlation with the phase of a disease; measuring the amount of this protein will then help us to better assess the state of the disease.

Reliable biomarkers can therefore also help to determine whether a particular therapy is having the desired positive effect on a disease, as the levels of the biomarkers should be responsive to effective treatments.

Research is being conducted to find a dependable set of biomarkers for SMA, which will be an invaluable tool for helping to assess the effectiveness of potential therapies in SMA clinical trials.

Progress with SMA Biomarkers


11th March: Biogen announced interim 6-month data from the RESPOND Trial of Spinraza™ that indicates the treatment is able to reduce levels of the biomarker Neurofilament light chain (NfL) in the blood.

The RESPOND Trial is a phase 4 study evaluating the benefit of Spinraza™ in infants with SMA previously treated with Zolgensma™. Only those who have been determined by an investigator to have the potential for additional clinical improvement have been included in the trial.

The latest reported data show that NfL levels in the blood were reduced in almost all participants treated with Spinraza™ for 6 months. As expected, neurofilament at baseline was increased in almost all participants compared with unaffected children of a similar age.

These positive data support that Spinraza™ treatment after receiving Zolgensma™ is having a positive effect on the blood biomarker neurofilament, suggesting that the dual treatment approach can have added benefit in, at least some, people with SMA.


22nd April: At the 73rd American Academy of Neurology (ANN) Annual Meeting, Biogen presented new data in 75 patients from the CHERISH / SHINE studies of Spinraza which builds upon the body of evidence that neurofilament levels in blood warrant further evaluation as a biomarker for assessing treatment response in SMA.

Data showed that higher neurofilament levels at baseline were, on average, associated with greater improvements in motor function scores among Spinraza-treated individuals with later-onset SMA. Measuring neurofilament levels has been integrated as an exploratory endpoint in the DEVOTE and RESPOND studies.


10th May: Biogen presented data at the American Academy of Neurology 2019 conference on a potential biomarker for SMA.

Researchers have found that raised levels of a protein called pNF-H in blood plasma indicate neurological damage and have potential to predict condition activity. The advantage of pNF-H is that it is present in blood and therefore easily measured.

The scientists showed that the level of pNF-H was higher in individuals with SMA than those without SMA. Individuals from the NURTURE, ENDEAR and CHERISH studies treated with Spinraza experienced rapid pNF-H declines followed by stabilisation at lower levels, indicating that pNF-H can correlate with condition severity and progression.

pNF-H is raised in several other nervous system conditions, and is therefore not specific to SMA. Nevertheless, pNF-H is likely to be a valuable biomarker for SMA, and the presented results are part of on-going work to identify biomarkers that could provide insight on condition progression in SMA.

The Research Paper: Neurofilament as a potential biomarker for spinal muscular atrophy >


24th May: The results from the Biomarkers for SMA (BforSMA) clinical study were published in the open access, scientific journal PLoS One. The study aimed to identify a set of biomarkers that correlate well with the severity of the disease.

108 children aged 2-12 with a broad range of SMA severity (17 Type I, 49 Type II, 42 Type III) were enrolled in a single evaluation study performed in 18 centres across North America. Blood and urine samples were collected from patients and 22 healthy, age-matched control donors, and then analysed for their protein, metabolite (small molecules produced by metabolism) and gene transcript (messenger RNA) content.

Using gross motor function as assessed by the Modified Hammersmith Functional Motor Scale (MHFMS) as the primary outcome measure (along with a number of secondary clinical measures), a total of 200 candidate biomarkers were shown to correlate with MHFMS score. These included 97 proteins and 59 metabolites found in plasma (the liquid component of blood), and 44 urine metabolites.

In collaboration with the SMA Foundation, Myriad RBM had launched a biomarker panel (SMA-MAP) based on the findings from this study (see below):

The PLoS One publications:

Candidate Proteins, Metabolites and Transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study

Evaluation of SMN Protein, Transcript, and Copy Number in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study

5th April: The SMA Foundation and Myriad RBM announced the launch of SMA-MAP, a biomarker assay panel for SMA. Using their unique, patented technology, RBM had designed a standardised set of tests to assess the levels of protein biomarkers specific to SMA, which could be used to evaluate disease severity and stage of progression.

In January of this year, RBM announced it would be processing plasma (the liquid component of blood) samples from SMA patients collected in the previously performed, multicentre Biomarkers for SMA (BforSMA) clinical study, which was conducted by BG Medicine and sponsored by the SMA Foundation.

Using these samples, a set of candidate biomarkers was identified, which were then either confirmed or rejected by testing of additional samples collected by the Pediatric Neuromuscular Clinical Research Network in a longitudinal study of SMA.

The use of SMA-MAP would allow clinical researchers to assess the levels of 27 different validated SMA biomarkers.

This collaborative effort was complementary to the NeuroNEXT initiative (see below).

2nd April: The Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) – an initiative overseen by the United States National Institute of Neurological Disorders and Stroke (NINDS) aimed to identify biomarkers associated with hundreds of different neurological diseases and announced that SMA would be the first disease on which a clinical study to find biomarkers would be performed.

Neuronext Website >

Research is taking place to evaluate digital tools that expand on traditional clinical assessments and incorporate more sensitive measures to help better predict and monitor the course of SMA.

In consultation with SMA experts, Biogen has developed a conceptual clinical framework to evaluate the potential value of Konectom™. This is a mobile application designed to enable adults living with SMA to quantitatively and remotely self-assess motor function in their daily lives.

Currently used only in research settings, Konectom™ leverages smart sensing technologies like touchscreen and accelerometry, to capture tangible data when studying neurological diseases.

In SMA, monitoring fatigue and smartphone typing skills may be useful to assess functional impact across a broad range of patients with varying levels of condition severity. It is hoped that this new technology will provide a more accurate and complete picture of how SMA impacts a person’s daily life.