What Is a Biomarker?
A biomarker is a kind of biological “fingerprint” – something about a living thing that can tell doctors or scientists something about that organism. They’re extremely important in diagnosing and managing diseases.
Some common biomarkers associated with diseases include blood glucose levels for diabetes or LDL cholesterol for heart disease. The search for more reliable biomarkers for diagnosing Amyotrophic Lateral Sclerosis (ALS) and measuring disease progression is one of the most vital challenges facing the ALS research community.
How Is ALS Disease Progression Currently Tracked?
Today, doctors and researchers must rely on clinical observations and subjective questionnaires like the revised ALS Functional Rating Scale (ALSFRS-r) to track disease progression. The ALSFRS-r can be an effective tool, but 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.
Why More Reliable Biomarkers Matter for ALS Clinical Trials
More reliable biomarkers would give individuals and their medical care teams a powerful tool to more accurately track ALS disease progression. Additionally, they would 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.
Clinical Indicators Currently Used in ALS Diagnosis and Treatment
There are many clinical indicators that are currently used in the diagnosis and treatment of ALS, including:
- Respiratory function
- MRI imaging of parts of the nervous system
- The presence of proteins associated with certain genetic mutations
- Body weight
However, a biomarker that is used as an endpoint for a clinical trial in the US must go through a stringent validation process. While there are a handful of approved biomarkers available to ALS clinical researchers, and some other promising potential candidates, more are needed to provide robust alternatives to the subjective measures of the ALSFRS-r survey.
How ALS TDI Is Working to Identify Potential Biomarkers
At the ALS Therapy Development Institute (ALS TDI), we are working through our ALS Research Collaborative (ARC) – the longest running natural history study in ALS – to partner with people with ALS all over the world to collect data and to search for potential biomarkers.
In-Home Blood Collection Program
These efforts include our first-in-kind In-Home Blood Collection program, which allows ARC participants to contribute regular blood samples by mail without leaving their homes. By studying these samples over time, we aim to identify more potential blood-based biomarkers that could correlate with disease progression.
In 2022, ALS TDI received a grant from the Department of Defense (DOD) to fund an expansion of this program, along with more advanced sample testing with the potential to reveal new protein biomarkers of ALS.
LifeArc Collaboration
ALS TDI is currently collaborating with LifeArc, one of the United Kingdom’s leading charitable biomedical research organizations. Together, ARC researchers are working with LifeArc to identify and validate blood-based biomarkers for ALS.
Using blood sample data from the ARC study, this program aims to enhance early diagnosis and monitor therapeutic responses to treatments in clinical trials. We have recently identified preliminary markers that could predict the rate of disease progression, paving the way for earlier diagnosis and improved treatment monitoring.
Digital Biomarkers
In addition to using biological samples, ARC researchers are working to use data to create digital biomarkers — AI algorithms that can analyze disease to provide objective measurements — for tracking ALS progression. Some participants in the program are provided with digital accelerometers to be worn on the arms and legs to generate movement data and asked to periodically record voice messages to keep track of vocal function. ALS TDI and several collaborators have utilized these data to develop five prototype digital biomarkers.
ALS TDI is currently working with the Critical Path Institute (C-Path) to evaluate ARC Study voice and accelerometer data as potential clinical trial outcome measures – advancing tools that could make ALS trials more sensitive, patient-centered, and better able to detect meaningful change.
How You Can Participate in Research with ALS TDI
Anyone diagnosed with ALS and asymptomatic carriers of ALS-related genetic mutations can participate in the ARC study and help contribute to this critical research.
To learn more about the ALS Research Collaborative, click here.
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Frequently Asked Questions
What is a biomarker?
A biomarker is a kind of biological “fingerprint” – something about a living thing that can tell doctors or scientists something about that organism. Common examples include blood glucose levels for diabetes and LDL cholesterol for heart disease.
How is ALS disease progression tracked today?
Doctors and researchers primarily rely on clinical observations and subjective questionnaires like the revised ALS Functional Rating Scale (ALSFRS-r), which depends on an observer’s assessment of a person’s abilities rather than an objective measurement.
Why do ALS clinical trials need better biomarkers?
Many ALS trials rely heavily on the ALSFRS-r, using a slowing 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 of whether treatments are helping subjects.
What clinical indicators are currently used for ALS?
Current clinical indicators include respiratory function, MRI imaging of parts of the nervous system, the presence of proteins associated with certain genetic mutations, and body weight. A biomarker used as a clinical trial endpoint in the US must still go through a stringent validation process.
What is the ALS Research Collaborative (ARC)?
The ALS Research Collaborative (ARC) is the longest-running natural history study in ALS. Through the ARC, ALS TDI partners with people with ALS all over the world to collect data and search for potential biomarkers.
What is ALS TDI's In-Home Blood Collection Program?
It is a first-in-kind program that allows ARC participants to contribute regular blood samples by mail without leaving their homes, so researchers can study the samples over time to identify potential blood-based biomarkers that could correlate with disease progression. In 2022, ALS TDI received a grant from the Department of Defense (DOD) to fund an expansion of this program, along with more advanced sample testing with the potential to reveal new protein biomarkers of ALS.
What is ALS TDI's collaboration with LifeArc?
ALS TDI is collaborating with LifeArc, one of the United Kingdom’s leading charitable biomedical research organizations, to identify and validate blood-based biomarkers for ALS using blood sample data from the ARC study. The program aims to enhance early diagnosis and monitor therapeutic responses to treatments in clinical trials, and preliminary markers that could predict the rate of disease progression have already been identified.
What are digital biomarkers?
Digital biomarkers use data, rather than biological samples, to track ALS progression. Some ARC participants wear digital accelerometers on their arms and legs to generate movement data and periodically record voice messages to track vocal function. ALS TDI and its collaborators have used this data to develop five prototype digital biomarkers, and are working with the Critical Path Institute (C-Path) to evaluate this voice and accelerometer data as potential clinical trial outcome measures.
Who can participate in ALS TDI's ARC study?
Anyone diagnosed with ALS, as well as asymptomatic carriers of ALS-related genetic mutations, can participate in the ARC study and help contribute to this critical research.