28 May 2026

The neurodegenerative disorder amyotrophic lateral sclerosis (ALS) is currently diagnosed through a process of exclusion, which can be lengthy and lead to delays in treatment.

In a review published in Neuroscience & Biobehavioral Reviews, Rafael López-Blanch and colleagues proposed a framework for a biomarker-driven precision medicine approach to diagnosing, monitoring, and treating ALS. To do this, the authors examine the biomarkers currently linked to ALS, linking each biomarker modality to its role in ALS detection and treatment.

First, the authors note that fluid biomarkers, including neurofilament light chain, phosphorylated neurofilament heavy chain, inflammatory cytokines, microRNAs, and proteins in blood or cerebrospinal fluid, can be used to assess neuronal injury, neuroinflammation, and RNA processing abnormalities. This makes these biomarkers valuable for the identification of ALS in presymptomatic individuals, along with the longitudinal tracking of neurodegeneration in patients diagnosed with the condition.

Next, imaging biomarkers, such as structural and diffusion MRI of the motor cortex, corticospinal tracts, and spinal cord, provide objective measures of upper motor neuron degeneration and extra-motor involvement.

Electrophysiological biomarkers, meanwhile, including high-density electromyography, motor unit number, transcranial magnetic stimulation, and electrical impedance myography, offer non-invasive methods for assessing functional alterations in motor neurons and cortical circuits that precede symptoms, as well as the progressive loss of lower motor neurons.

Finally, variants in genes such as C9orf72, SOD1, FUS, and TARDBP can be used for early diagnosis and to stratify patients into subtypes.

Overall, the authors emphasize that integrating these biomarkers into ALS diagnosis and care must be done using a multimodal, stage-specific approach.

This approach could be useful for improving diagnostic accuracy in ALS, along with biomarker-driven stratification of patients, which could enable future clinical trials to focus on homogeneous patient subsets and use biomarkers as secondary end points. As the authors note, this precision medicine approach could transform ALS treatment and greatly improve patient outcomes in this fatal neurodegenerative disease.

Source: docwirenews