By: Grace Huff
At the Norman Fixel Institute for Neurological Diseases, research fellow A. Enrique Martinez-Nunez, M.D., Movement Disorders neurologist and ALS research fellow, is working to answer one of the most urgent questions in neurodegenerative disease: why does ALS progress differently from one patient to another? As the institute’s ALS research fellow, made possible through a philanthropic gift from former University of Florida head football coach Billy Napier, Martinez-Nunez is helping uncover new insights that could reshape how clinicians understand and manage the disease.
In a new study in BMJ Neurology Open, Martinez-Nunez and collaborators analyzed data from more than 8,600 people living with ALS, using the National ALS Registry to examine how environmental and occupational exposures may affect disease progression. Rather than focusing only on whether exposures contribute to developing ALS, the team asked a different and equally important question: once someone has ALS, do those past exposures change how the disease behaves?
The answer appears to be yes. This study found that individuals with prior exposure to herbicides, metal dust and fumes and oil-based paints experienced a faster decline in physical function over time.“The most striking finding was how consistent the effects were across very different types of exposures,” Martinez-Nunez explained, suggesting a broader pattern in how environmental factors may influence disease progression. The research also revealed that individuals with a history of head injury began the study with worse overall physical function, pointing to another factor that may shape disease severity from the outset.
These findings suggest that environmental exposures may not only play a role in the risk of developing ALS but may also act as modifiers of how aggressively the disease progresses. That distinction has meaningful implications for patient care. Understanding a patient’s occupational and environmental history could help clinicians better anticipate disease trajectory and tailor monitoring and supportive care earlier in the course of the disease.
While the study draws on large-scale registry data, Martinez-Nunez emphasizes that it is an important first step. Future research will aim to measure exposures more precisely and better understand the biological mechanisms driving these effects, including how substances like herbicides or metal particles may contribute to motor neuron damage. Ultimately, the goal is to translate these insights into real-world impact, through improved clinical care, how we design clinical trials and how we counsel patients about their disease.
In addition to this work in ALS, Martinez-Nunez was recently awarded a prestigious NIH K12 career development award, which supports early-career physician-scientists as they build independent research programs. The award will allow him to expand his work using advanced tools such as brain imaging and machine learning to better predict how neurological diseases progress. Although the K12 focuses on Parkinson’s disease, the skills and methods developed through this training will directly strengthen future work in ALS and other neurodegenerative conditions.
At the Fixel Institute, where interdisciplinary research and patient-centered care are at the core of its mission, Martinez-Nunez’s work reflects a broader effort to better understand complex neurological diseases and improve outcomes for the patients and families who face them every day.