For years, the revised ALS Functional Rating Scale (ALSFRS-r) has been the standard for tracking the disease progression of people living with amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease. The ALSFRS-r is a survey designed to be filled out by peope with ALS, physicians and nurses caring for people with ALS, or ALS caretakers, at regular intervals. It asks the respondent about the person’s ability to complete 12 different tasks such as speaking, swallowing, handwriting, and walking. The ratings are done on a scale from zero to four ¬– zero meaning they are incapable of accomplishing the task, and four meaning they can do it with no difficulty. These ratings are then totaled to make one overall score, from zero to 48.

Limitations of the ALSFRS-r

The ALSFRS-r can be an effective tool, but is limited by the fact that it is a subjective measure of a person’s abilities – it relies on the observer’s assessment about how the disease is affecting a person’s ability to complete the tasks being evaluated by the survey. While the test has been designed to provide as accurate a measure of disease progression as possible – and to make these measurements as consistent as possible from subject to subject – there is no guarantee that any two respondents will rate the relative progression with the same score.

Biomarkers as a Measure of Disease Progression

This is one reason why researchers are so motivated to discover more reliable biomarkers for ALS. A biomarker is any biological measure that tells us something about a disease, like insulin levels for diabetes or LDL cholesterol for heart disease. For ALS, a blood-based biomarker like these examples could be particularly useful – something that could be detected through a simple blood test. ¬

More reliable biomarkers would also have implications beyond helping individuals and their caregivers track their disease progression – they would also be enormously helpful for clinical trials. Many trials for ALS rely heavily on the ALSFRS-r to see if treatments appear to be having any effect – often using a slowing down or stopping in the decline of a subject’s scores as an important endpoint. A reliable biomarker or set of biomarkers could give researchers clear – and objective – measures to see if treatments are helping subjects.

There are many biomarkers for ALS that are currently used in the diagnosis and treatment of the disease as well as the earlier stages of drug development – things such as respiratory function, MRI imaging of parts of the nervous system, the presence of proteins associated with certain genetic mutations, or even body weight. However, to be used as an endpoint for a clinical trial in the US, biomarkers must go through a stringent validation process. While there are a handful of approved biomarkers available to researchers, and some other promising potential candidates, more are needed to provide robust alternatives to the subjective measures of the ALSFRS-r survey.

ALS TDI’s Work to Identify Potential Biomarkers

At the ALS Therapy Development Institute (ALS TDI) we are using our Precision Medicine Program (PMP) to partner with people with ALS all over the world to collect data and to search for potential biomarkers. These efforts include our first-in-kind In-Home Blood Collection program, which allows PMP participants to contribute regular blood samples by mail without leaving their homes. By studying these samples over time, we hope to identify more potential blood-based biomarkers that could correlate to disease progression.

Until reliable biomarkers are discovered and approved, the ALSFRS-r remains a helpful tool to track disease progression, despite its inherent limitations. To learn more ALS TDI’s efforts to find effective treatments for ALS, including our search for potential biomarkers, click here.