How ALS TDI Is Discovering New Biomarkers for ALS

What Is a Biomarker?

A biomarker is a kind of biological "fingerprint," something that gives doctors and scientists information about a living organism. They're extremely important in diagnosing and managing diseases. For example, blood glucose levels are a key biomarker for diabetes, and LDL cholesterol is a biomarker for heart disease.

Why ALS Needs More Reliable Biomarkers

The search for more reliable biomarkers for amyotrophic lateral sclerosis (ALS) is one of the most vital challenges facing researchers working to end the disease. More reliable biomarkers for ALS could:

• Speed up the diagnosis process
• Improve clinicians' ability to measure progression
• Make clinical trials faster and more efficient

The ARC Study: Powering Biomarker Research at ALS TDI

At the ALS Therapy Development Institute (ALS TDI), we are working to uncover potential biomarkers through our ALS Research Collaborative (ARC) Study — the longest running natural history study in ALS. Through the ARC Study, ALS TDI researchers have been partnering with people with ALS from all over the world to collect comprehensive data about the disease since 2014.

These data include biological samples and digital measures of disease progression that provide essential raw data necessary to search for potential blood-based and digital biomarkers.

What Are Digital Biomarkers for ALS?

A digital biomarker works similarly to more commonly known blood-based biomarkers, providing objective and quantifiable measures of a disease. However, rather than testing for levels of compounds in a biological sample, they analyze electronic data about movement, speech, and other biometric measures of disease.

ALS TDI's digital biomarkers utilize data from voice and movement recordings collected through the ARC Study. ARC participants provide these data by submitting monthly recordings of themselves reciting a series of phrases and wearing accelerometers — wrist and ankle-worn devices that track movement. ALS TDI and our collaborators have developed a series of statistical models, some of which deploy artificial intelligence (AI) technologies that can assign objective scores to these data. These digital biomarkers have the potential to help clinicians accurately track disease progression and serve as endpoints in clinical trials.

Five Prototype Digital Biomarkers Developed by ALS TDI

ALS TDI scientists and our research partners have developed five prototype digital biomarkers of ALS:

• Voice scoring algorithms (2022): ALS TDI and Google researchers published a paper describing a set of voice scoring algorithms to analyze speech recordings. This work was part of Project Euphonia, a larger effort led by Google and initiated with data from the ARC Study to develop new tools to support people with conditions that affect speech, like ALS.
• Movement-scoring algorithms from prescribed exercises (2022): This same publication included movement-scoring algorithms that could analyze recordings from accelerometers worn while participants perform a prescribed set of exercises.
• Daily activity accelerometer biomarker (2023): ALS TDI and collaborators at Massachusetts General Hospital (MGH) published a paper demonstrating that data gathered with accelerometers worn during normal daily activities could also serve as a promising digital biomarker.
• Refined daily-activity machine-learning algorithm (2024): ALS TDI and researchers from MGH, the Harvard T.H. Chan School of Public Health, and the IRCCS Istituto Auxologico Italiano reported on new AI tools for analyzing movement data, including a refined machine-learning algorithm capable of analyzing data from accelerometers worn during day-to-day life.
• Refined exercise-based machine-learning algorithm (2025): Building on the 2024 publication, ALS TDI and our collaborators published a further refined algorithm capable of analyzing accelerometer data gathered while participants perform a series of exercises.

Could Digital Biomarkers be used as Outcome Measures for Clinical Trials?

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 will make ALS trials more sensitive, patient-centered, and better able to detect meaningful change.

How ALS TDI Is Searching for Blood-Based Biomarkers

In addition to our work to develop digital biomarkers for ALS, ALS TDI has several active research programs dedicated to discovering blood-based biomarkers for ALS.

In-Home Blood Collection Program

Many of these efforts are made possible through our In-Home Blood Collection initiative. This program allows ARC participants to contribute regular blood samples 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 for 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.

How You Can Help Power ALS TDI's Biomarker Discovery Efforts

All of ALS TDI's biomarker discovery work is made possible by the selfless contributions of ARC participants. Anyone diagnosed with ALS and asymptomatic carriers of ALS-related genetic mutations can participate in the ARC Study and help contribute to this important research. All participation is remote and can be completed from home.

In addition to biological samples, voice recordings, and accelerometer data, ARC participants also share data such as electronic health records, ALSFRS-r scores, and surveys about their background and lifestyle. These data are used to power research by ALS TDI and our collaborators and are shared with the worldwide ALS research community through the ARC Data Commons.

To learn more about the ALS Research Collaborative, click here.

Frequently Asked Questions

What is a biomarker?

A biomarker is a kind of biological "fingerprint," something that gives doctors and scientists information about a living organism. They're extremely important in diagnosing and managing diseases. 

Why do we need better biomarkers for ALS?

More reliable biomarkers for ALS could speed up the diagnosis process, improve clinicians' ability to measure progression, and make clinical trials faster and more efficient.

What is a blood-based biomarker?

A blood-based biomarker is something that can be measured in a blood test to give doctors or scientists information about a disease. Common blood-based biomarkers include blood glucose levels for diabetes and LDL cholesterol for heart disease.

What is a digital biomarker?

A digital biomarker works similarly to more commonly known blood-based biomarkers, providing objective and quantifiable measures of a disease. However, rather than testing for levels of compounds in a biological sample, they analyze electronic data about biometric measures of disease.

What is the ARC Study?

The ALS Research Collaborative (ARC) Study is the longest-running natural history study in ALS. Through the ARC Study, ALS TDI researchers have partnered with people with ALS from all over the world to collect comprehensive data about the disease since 2014. A major goal of the ARC study is to discover new blood-based and digital biomarkers for ALS.

What to Do Next:

• Learn more about the ARC Study and sign up to participate
• Read more about ALS TDI’s Active Research Projects
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