Biomarker Discovery at ALS TDI

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.

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, and 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.

Digital Biomarkers

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

These prototype digital biomarkers developed by ALS TDI include:

• In 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.
• This 2022 publication also included movement-scoring algorithms that could analyze recordings from accelerometers worn while participants perform a prescribed set of exercises.
• In 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.
• In 2024 and 2025, ALS TDI and researchers from MGH, the Harvard T.H. Chan School of Public Health, and the IRCCS Istituto Auxologico Italiano reported on two studies developing new AI tools for analyzing movement data. These papers describe refined machine-learning algorithms capable of analyzing data from accelerometers worn during day-to-day life and while performing a series of exercises, respectively.

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.

Many of these efforts are made possible through our first-in-kind In-Home Blood Collection program. This 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 of ALS.

Building on this, 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.

What to Do Next:

• Learn more about the ARC Study and sign up to participate
• Read more about ALS TDI’s Active Research Projects
• Subscribe to our newsletter for more stories like this delivered to your inbox