Lifetime Achievement Award Recognizes Catalyst of ALS Therapy Research and Development
Key Findings
- The award acknowledges a career spent building worldwide partnerships and collaborations that have advanced patient access to new research and therapies
- Ongoing efforts focus on streamlining pathways to earlier and more accurate diagnosis to capitalize on therapies showing promise in early-onset ALS
- New initiatives are expanding clinical trials access for both researchers and patients to maximize opportunities to discover effective therapies
- Merit Cudkowicz, MD, MSc, highlights the importance of open collaboration and patient-centered approaches to research and care that optimize outcomes for everyone
In April 2025, the American Academy of Neurology presented the Lifetime Achievement Award for Clinically-relevant Research to Merit Cudkowicz, MD, MSc, director of the Sean M. Healey and AMG Center for ALS. The award recognizes Dr. Cudkowicz's efforts in creating worldwide collaborations that have transformed the search for therapies targeting neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).
Subscribe to the latest updates from Neuroscience Advances in Motion
Since co-founding the Neurological Clinical Research Institute at Massachusetts General Hospital in 1994 and the Northeast ALS (NEALS) Consortium in 1995, Dr. Cudkowicz's focus on building partnerships has driven progress in finding treatments for ALS. "Everything that we've accomplished has been the result of working together to improve the lives of ALS patients," she explains.
During Dr. Cudkowicz's acceptance of the award, she discussed the importance of open collaboration, including with patients, and some of the progress being made in fighting an incurable disease.
Facilitating Early Diagnosis
Early and accurate diagnosis of ALS is critically important to ensuring patients receive appropriate care. This includes access to ALS-targeted therapies and resources, as well as eligibility for clinical trials.
However, diagnosing ALS, especially in its early stages, is exceptionally challenging due to:
- The variability and subtlety of early symptoms
- Overlap in symptom presentation with other neurological diseases
- Criteria requiring multiple clinical presentations before diagnosis
- Lack of definitive diagnostic biomarkers
The average time from symptom onset to ALS diagnosis ranges from 11 to 15 months, during which patients see numerous clinicians and often receive multiple misdiagnoses. For those with ALS, time lost cannot be recovered, whereas early diagnosis can open doors to medical, financial, and emotional resources.
To improve diagnostic speed and accuracy, a collaboration of clinicians, caregivers, foundations, industry representatives, and ALS patients identified barriers to early ALS diagnosis and developed strategies to address them. The resulting thinkALS tool now provides primary care physicians and neurologists with lists of clinical features for or against an ALS diagnosis that can help drive appropriate referral decisions.
"Data support clinicians' collective experience that early intervention is the key to maximizing treatment effect," says Dr. Cudkowicz. "The next step in supporting diagnostic accuracy involves identifying markers that validate the clinical presentations we believe are tied to ALS."
Identifying the Signals That Define ALS
Finding ALS-specific markers requires overcoming obstacles related to variabilities in disease presentation, including:
- Heterogeneity: A broad spectrum of symptoms and progression rates hinders the search for consistent molecular patterns across patients
- Dynamics: Disease stage alters different markers in different ways, requiring long-term, consistent sampling of a diverse range of patients at various times
- Pathology: Shared features with other diseases complicate definitions of what an ALS-specific marker should look like
Accelerating Medicines Partnership for ALS (AMP ALS) is a collaboration between government, industry, non-profit entities, academic researchers, and patient groups focused on identifying gaps in knowledge and overcoming challenges such as these. In partnership with AMP ALS, the Access for All in ALS (ALL ALS) consortium is engaged in identifying ALS-specific markers across a wide range of cohorts. ALL ALS is currently leading two national studies co-directed by the Barrow Neurological Institute and Mass General.
The ALL ALS PREVENT study investigates the earliest stages of ALS in asymptomatic but genetically at-risk individuals. The study collects data and biofluid samples to:
- Detect early markers of biological changes tied to ALS development before symptom onset
- Define subtle changes during ALS onset to create clinical tools enabling their detection
- Develop therapies targeting the biological and genetic profiles of those at risk of ALS
By contrast, ALL ALS ASSESS is a longitudinal study focusing on biomarker identification over a longer period (two years). This study involves a more diverse array of participants, including those currently living with ALS and healthy controls. The goals of the study are to:
- Collect medical histories, clinical outcomes, and biological samples every four months, as well as patient-reported outcomes and speech recordings once a month
- Create a biorepository of samples available to researchers across the landscape of neurological diseases
- Establish a collaborative network of research sites to expand care access for patients and share knowledge to accelerate progress in ALS treatment
Dr. Cudkowicz notes that what defines these efforts are the contributions of those with lived experience of ALS. From their input as collaborators with AMP ALS to participation in the studies, patient engagement in research is critical to its progress.
"Patients bring perspectives that guide research goals and decisions," she explains. "Their participation in all aspects of the process gives relevance to what we're trying to accomplish."
Expanding Access to New and Improved Therapies
Approximately 10% of patients have familial ALS, with around 70% of those carrying mutations in one of four genes (SOD1, C9orf72, TARDPB, and FUS). In 2023, the FDA approved tofersen (QALSODY) as the first therapy targeting a genetic cause of ALS (SOD1-ALS). Beyond the significance of a new therapy, approval reinforced the potential of antisense oligonucleotides (ASOs) for targeting the byproducts of mutated genes responsible for motor neuron death.
Mass General and the NEALS Consortium were instrumental in early investigations of tofersen and the use of ASO therapy. As a co-principal investigator on the Phase 1/2 trial of the drug, Dr. Cudkowicz observed ASO's ability to both decrease SOD1 levels and lower levels of a biomarker of axonal damage. Beyond the importance of those findings to tofersen's approval, the results initiated other trials targeting SOD1-ALS and expanded use of gene therapy for more common sporadic forms of ALS (QurAlis and Amylyx).
Recent positive outcomes support the therapeutic promise of ASOs for ALS patients, especially when administered early in the disease. Another result from the Phase 3 trial of tofersen showed that it not only stopped ALS progression but also allowed some patients to regain function. Those observations led to the ATLAS trial, which is currently evaluating the use of the drug in presymptomatic SOD1-ALS patients.
"What's exciting is that researchers in this field are rapidly innovating ways to generate new and more effective therapies," says Dr. Cudkowicz. "The common theme of these promising outcomes is the importance of early diagnosis and treatment."
Learning Smarter and Faster
Optimizing outcomes for ALS patients from experimental therapies continues to be a guiding principle at Mass General. Dr. Cudkowicz was the driving force behind establishing the HEALEY ALS Platform Trial and redefining what an effective clinical trial can look like. Recent publication of outcomes from the first four regimens evaluated using this protocol offers evidence of the speed and effectiveness of their patient-centered approach to drug discovery.
Two additional initiatives at Mass General that Dr. Cudkowicz leads with her collaborators underscore the recognition that efficiency breeds discovery and faster patient access to effective treatments:
- The Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) program offers researchers infrastructure and resources to conduct studies on rare neurodegenerative disorders. The goal is to capitalize on the collective experience of academic, industry, and private partners to expedite therapy discovery and development.
- The ALS MyMatch program uses patient biomarkers to match their biological profile to a particular treatment regimen being evaluated in an early clinical trial (Phase 2a). The goal is to target therapies to the right population at the right time by screening patients based on their likelihood of response to the treatment.
"The costs of developing and evaluating a drug for safety and efficacy are major roadblocks for small companies working to generate therapies for rare diseases," explains Dr. Cudkowicz.
For some drugs, failure due to an inadequate therapeutic response may be less a consequence of the drug's efficacy than the variability in disease presentation among the patients in which it was tested.
"These programs are designed to position new therapies for success by evaluating them in patients prescreened to potentially realize the greatest therapeutic effect," she explains. "The result would be a win for everyone involved."
Progress Driven by and for Patients
Dr. Cudkowicz says that she and her colleagues view the neurological research centers at Mass General as having no walls.
"The goal was to build and maintain worldwide collaborations that would continue to grow through training and mentorship opportunities," she says. "The focus remains on sharing what we learn in order to keep collectively getting better at what we do."
She emphasizes that the voices of patients are critical to improving care delivery and research study design. "I learned early in my career about the importance of simply caring for patients' symptoms, both physical and emotional," says Dr. Cudkowicz. "I'm proud that the center we've created here targeting ALS is built on a foundation of what our patients and families tell us they need."
Two voices in particular changed the course of what Mass General offers ALS patients. Dr. Cudkowicz recalls a letter from a patient's daughter explaining that despite her father's inability to travel, he wanted to somehow remain connected to their team and research. This led to the establishment of the Daniella Lipper ALS House Call Program, the success of which is now driving its expansion to other centers nationwide.
Another letter addressed how to explain ALS to children. A patient's husband asked whether something similar to that available to cancer patients existed for ALS patients.
"We immediately contacted the founder of that program and requested help," Dr. Cudkowicz explains. Since 2019, the Daniella Lipper ALS Parenting at a Challenging Time program has provided support to families helping children cope with an ALS diagnosis in a parent or grandparent.
"Our collective success is a direct reflection of how patients make us better clinicians and researchers," says Dr. Cudkowicz. "Although finding effective treatments takes time, satisfaction comes with finding ways to immediately make a difference in their lives."