National Clinical Research Consortium Making ALS Research Accessible to All

Recent years have seen the emergence of numerous FDA-approved, disease-modifying drugs for amyotrophic lateral sclerosis (ALS). These novel therapeutics have given hope to patients and families facing what was once thought to be an untreatable disease.

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Still, many aspects of ALS remain a mystery, especially how it progresses in people over time. In response, the National Institutes of Health (NIH) established and funded a national clinical research consortium called Access for ALL in ALS (ALL ALS) in 2023. This multi-institutional study aims to create a comprehensive, inclusive data set that helps address critical scientific and clinical questions to spur ALS drug development.

Massachusetts General Hospital, a founding member of Mass General Brigham, is one of two institutions that the NIH selected to serve as regional coordinating centers for ALL ALS. The other is Arizona's Barrow Neurological Institute. The respective lead principal investigators are James D. Berry, MD, MPH, and Robert P. Bowser, PhD.

The two centers oversee a pair of related studies spanning 37 research sites throughout the United States and Puerto Rico:

• ASSESS, which collects data on individuals living with ALS and individuals living without ALS (controls) to track disease progression and identify new biomarkers
• PREVENT, which focuses on understanding the earliest stages of the disease in people who have a known or suspected genetic variant that increases their risk for developing ALS 

All clinical health data collected through ALL ALS are forwarded to the ALS Knowledge Portal, which the Accelerating Medicines Partnership in ALS Program developed to allow for sharing with the research community. The biosamples go to BioSEND, an Indiana University-based biorepository funded by the National Institute of Neurological Disorders and Stroke. These samples are accessible to external investigators.

"We have brought and maintained a strong focus on the availability of all the data and samples we collect," Dr. Berry says. "So, we can proudly tell the community, and in particular people who are considering joining a study, that ALL ALS is creating an open science platform and that their contributions will be broadly accessible by ALS researchers and meaningful in advancing science."

A direct result of the ACT for ALS

ALL ALS has its roots in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS). This legislation, passed in 2021, called for the establishment of a partnership involving the NIH, FDA, and at least one higher education institution or nonprofit organization to support the development of drugs for ALS and other rare neurodegenerative diseases.

The NIH subsequently held meetings with stakeholders across the ALS community, including patients, clinical researchers, clinicians, and bench scientists. These conversations identified the need for a large, national study that would collect prospective data and biofluids, and share these data to advance ALS research.

"The ACT for ALS was the result of a groundswell of grassroots organizing to support more ALS research and collaboration," Dr. Berry says. "The funding that was made available through the ACT for ALS, in turn, is what made ALL ALS possible."

Given how rapidly promising new ALS drugs are being developed, Dr. Berry adds, the launch of ALL ALS came at an opportune moment.

"We are now seeing a robust pipeline of gene therapies, antisense oligonucleotides, RNA therapies, antibody therapies, cell therapies, and highly targeted small molecule therapies that are all entering clinical trials," he says. "This heralds a new ALS era of biologically targeted therapy development that meaningfully increases our chances of success compared to a few years ago."

A closer look at ASSESS and PREVENT

According to a paper published in Muscle & Nerve, "ALL ALS will provide a large-scale, centralized, and readily accessible infrastructure for the collection and storage of a wide range of data from people living with ALS (symptomatic cohort) or who may be at risk of developing ALS (asymptomatic ALS gene carriers)."

ASSESS, which focuses on understanding individuals' unique experience of ALS, is enrolling two cohorts of participants who will contribute longitudinal data and biosamples. One cohort will consist of symptomatic ALS participants, while the other will comprise control participants. To minimize burden, participants living with ALS can take part on-site or remotely.

"As long as they have an internet connection, people living with ALS can participate fully from the comfort of their own home," says ALL ALS patient navigator Emma Allen. "They can have telehealth research visits with their site team, and we can collect data via digital surveys for patient-reported outcomes, digital speech assessments, and remote cognitive testing."

"Participants living with ALS never have to set foot in clinics if they don't want to," adds Emma Joy Goldberg, PhD, clinical outreach program manager at Mass General. "We can even send a phlebotomist into the home for blood tests."

PREVENT is the first large-scale, multicenter study of people who are healthy but may carry a gene that puts them at high risk for developing ALS. (“The most common ALS genes are C9orf72, SOD1, TARDBP and FUS,” according to this 2024 paper.) The researchers hope to generate knowledge that could lead to more informative, targeted, and personalized drug development, bringing the field closer to the goal of halting, repairing, and/or preventing ALS.

"We've designed a protocol that follows these individuals for up to three years," Dr. Goldberg says. "If they are diagnosed with ALS within that timeframe, they can transition to ASSESS to be tracked."

Making ALS research accessible to all

Traditionally, enrollment and continued participation in ALS studies have been challenging due to factors such as:

• Narrow inclusion criteria: Time since diagnosis, time since disease onset, and other inclusion criteria leave many community members ineligible.
• Distance to research site: Many community members live in a research desert or attend a clinic that does not offer research opportunities.
• Disease severity: As ALS progresses, participants often drop out due to difficulties with traveling to the research site.

A guiding principle of ALL ALS is to make ALS research accessible to all. As such, the inclusion criteria are quite broad. Since on-site visits are not required for ASSESS participants living with ALS, these individuals can be recruited from far and wide. And the availability of remote options boosts recruitment and retention.

As a result, ALL ALS is unprecedented in terms of size and scope. So far, the program has recruited an ethnoculturally and socioeconomically diverse population of more than 1,700 people from 50 states and Puerto Rico.

"We've relied on established partners in the ALS community—clinicians, staff at all our sites, clinical liaisons—to recruit and help retain participants," Dr. Goldberg says. "Our aim is to enroll more than 2,000 participants. For many of these individuals, particularly those in rural areas, this represents their first opportunity to participate in an effort like this."

Community outreach goes beyond recruitment, Dr. Goldberg notes. "We're creating a community for the ALS population," she says. "We go to community events, do educational webinars, and create resources for patients and families, like newsletters that share updates on ALS research."

ALL ALS is well on its way to becoming the largest-ever observational/biomarker study of ALS in North America. Dr. Berry is eager to see the impact it makes in the years to come.

"With the ALL ALS consortium, we are working together to write the future story of ALS research,” he says. “The data, biospecimens, patient perspectives, and digital health technologies we collect today will form the basis for disease understanding for a decade. And with new techniques to analyze samples, decode genetics, and use AI to find signal in large datasets, we foresee rapid progress and a bright future ahead."

Patients interested in participating in ALL ALS can fill out this interest form or email the ALL ALS team for more information.

Learn more about Access for ALL in ALS

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