By Deborah Borfitz 

May 8, 2025 | A diagnosis of amyotrophic lateral sclerosis (ALS) is devastating news given to about 5,000 people in the U.S. each year. It is a rare central nervous system disease without a cure that relentlessly progresses, although death variably occurs anywhere from a few months to many years after symptoms first become noticeable, according to Robert Bowser, Ph.D., chief scientific officer and chair of translational neuroscience at the Barrow Neurological Institute in Phoenix. 

That heterogeneity makes diagnosis and treatment more challenging, but it also begs questions about why some people live longer. A major research initiative supported by the National Institutes of Health (NIH) aims to provide some long-awaited answers, says Bowser, who leads one of the coordinating centers for a pair of study protocols ambitiously looking to enroll 1,000 participants by this fall and 2,000 by next spring. “It is a heavy load; no one has ever done this before in ALS [aka Lou Gehrig’s disease].” 

Bowser is a principal investigator (PI) overseeing research efforts of the Access for All in ALS (ALL ALS) Consortium, a public-private consortium born out of the Accelerating Access to Critical Therapies for ALS Act that was signed into law at the end of 2021. Its mission is to facilitate ALS clinical research in drug development. 

A key feature of ALL ALS is its open science approach. The data and patient samples being collected in its studies will be made available to researchers around the world through both a web-based portal and a central biorepository at the NIH where all samples are being shipped, says Bowser.  

His counterpart is James D. Berry, M.D., chief of the division of motor neuron diseases and director of the Neurological Clinical Research Institute at Mass General Hospital. Both the east and west coordinating centers for ALL ALS have a lot of experience in conducting clinical research and trials, and Bowser has additionally been involved in managing other national biorepositories of ALS biofluids and post-mortem tissues. 

Together, they oversee a study team that includes 11 other PIs that coordinate enrolling participants in the ALL ALS protocols at 35 clinical sites nationwide: ASSESS for people living with the disease and healthy people who will act as comparators, and PREVENT for people who may be at genetic risk for ALS but do not have any symptoms of the disease. As of the end of April, the studies had a combined 429 participants—275 enrolled in ASSESS and another 154 in PREVENT—60 of whom are being engaged in a fully remote fashion, Bowser reports. 

“We’re actively looking at sites to bring on in states that currently don’t have [one],” he says. But the program incorporates the fully remote option to accommodate patients in geographies lacking a major ALS clinic, whereby participants are visited by a mobile phlebotomist for blood draws once per quarter, in addition to completing monthly online questionnaires and speech tasks.  

The advantage of having participants go to bricks-and-mortar sites is that they can undergo a more intensive battery of exams and researchers can thus collect more data on individual patients, says Bowser. Fully remote participation also has its benefits, notably the opportunity for those that would otherwise not have the ability to participate in research to do so, and to assess how well this approach works in terms of sample collection and data accuracy. 

Discovery Paths

The ASSESS and PREVENT protocols are biomarker-related studies that will enable patients with ALS and asymptomatic individuals harboring the gene mutations that cause the disease to be plugged into upcoming interventional drug trials, perhaps one or two dozen of which are underway at any one time, explains Bowser. Currently, many of these are small dose-finding safety studies. 

Participants in the PREVENT study are functioning normally but will be followed long-term to look for early signatures of disease onset. “Now, we will basically have a registrar of individuals who harbor specific gene mutations, so when clinical trials come on board that are targeting those mutations, we have individuals we can help quickly enroll,” he says. 

There is currently one ALS drug treatment approved by the U.S. Food and Drug Administration—Biogen’s Qalsody (tofersen)—and it is only for patients with mutations in the SOD1 gene (about 2% of ALS cases), adds Bowser. But the drug has made a “tremendous impact” on that patient population, measurably slowing progression of the disease and in some cases improving their strength—something that has “never been seen before... everyone always goes downhill.”  

A current trial called ATLAS enrolled people who don’t yet have symptoms but carry a SOD1 genetic mutation, he reports. The patient-derived samples and companion clinical data being collected in these studies of asymptomatic gene carriers will also allow more biomarker discovery studies to launch to discover more about how the onset of disease occurs.  

Marketing and Outreach

ALL ALS Consortium announced the launch of its official website at the end of March. Prior to this, recruitment was left to the individual study sites. 

In addition to now having a central hub for information about its initiatives and clinical research studies, the ALL ALS Consortium also has an operational outreach program that includes educational webinars about the two study protocols and engagement with patient-facing organizations on social media, Bowser says. These include not only established nonprofits like the ALS Association and Muscular Dystrophy Association, but also numerous groups formed by patients and their families. 

In the coming months, the ALL ALS Consortium will be ramping up marketing efforts to support its study enrollment goals. This includes outreach and communications with patients and families connected with the national ALS registry run by the Centers for Disease Control and Prevention, he notes.  

The “big agenda” here is to reach as many patients and family members as possible with the study opportunities, he says. “We are also enrolling healthy controls, so essentially anyone in this country can participate.” 

All healthy controls will need to physically go to one of the study clinics for an assessment to ensure their central nervous system is functioning properly, says Bowser. For the next two years, they would then be asked to complete online questionnaires and speech assessments, but not as frequently as the patients with ALS, and to come in for a blood draw once a year. They can also opt to provide cerebrospinal fluid (CSF), a biofluid that surrounds the brain and spinal cord and therefore may contain the earliest biomarker signatures of disease. 

Research Strides

Critical to the success of the research initiative is the collection of longitudinal blood and CSF samples from study participants, together with affiliated clinical and survey data and speech recordings, for the benefit of ALS investigators everywhere. A big problem currently is that such samples are a “finite resource” requiring dedicated effort to continuously replenish, Bowser says, given that ALS is a rare disease. 

The literature suggests that the typical time from diagnosis to death is only two to five years, but the reality is that it is highly variable, he adds, which complicates both the science and clinical trials. “Information about what is causing that heterogeneity is [therefore] really important.”   

Interest in ALS research in general, and the number of investigators making it their specialty, has increased over the past decade, Bowser says. That is unlikely to diminish unless NIH funding goes away. 

Plenty of research strides have been made in recent years to fuel excitement, he says, pointing to the use of patient-derived cells (induced pluripotent stem cells) that can be grown in the lab for research and matched with clinical data and biofluids on those same individuals. “Now, we can not only use the biofluids and look for biomarkers, but we use cells from patients themselves” to conduct drug screening studies that were previously conducted primarily in animal models.  

Genetic sequencing of samples being collected from ALS patients has been “a great boon to the drug development process,” says Bowser. It has also helped to identify causes and risk factors for the disease.  

“We’re getting closer and closer to improved treatments for our patients,” Bowser continues. “Right now, much of it is focused on genetic forms of ALS, but as we gain more knowledge around [disease] heterogeneity, we can start to have better treatments for the majority of patients who don’t harbor any gene mutations that we know of.”