New Grants Support Research on Myotonic Dystrophy and ALS in the Berglund Lab

By Erin Frick

ALBANY, N.Y. (June 24, 2025) — Two University at Albany researchers working in the RNA Institute at the College of Arts and Sciences have received new funding to support projects focusing on myotonic dystrophy (DM) and amyotrophic lateral sclerosis (ALS). 

Postdoctoral Fellow Cécilia Légaré was awarded $105,000 from the Myotonic Dystrophy Foundation to advance her work looking at effects of weight training on muscle cells in people living with myotonic dystrophy. Research Scientist Subodh Mishra received $207,000 from the Muscular Dystrophy Association to explore how an FDA-approved nutritional supplement could be used to help treat multiple neuromuscular diseases. Both researchers are members of the Berglund Lab.

Myotonic dystrophy (DM) and amyotrophic lateral sclerosis (ALS) are both rare progressive neuromuscular diseases. Myotonic dystrophy, which is a special area of focus at the RNA Institute, is characterized by muscle weakness and myotonia—an inability to relax muscles. Primarily affecting muscle tissue, DM also impacts the heart, eyes and brain. ALS is a disease of the nervous system which disrupts communication between nerve cells and impacts how a person with the condition moves, speaks and breathes.  

“We are fortunate to have two exceptional scientists leading exciting research in the lab that will directly benefit individuals and families affected by DM and ALS," said RNA Institute Director and Keith Hynes Endowed Professor Andy Berglund. “These prestigious awards recognize Cécilia and Subodh’s excellence and put them on the path of leading their own research groups in the future. 

How Weight Training Shapes Myotonic Dystrophy Progression 

Cécilia Légaré is from the Saguenay-Lac-Saint-Jean region of Quebec, which has the highest myotonic dystrophy prevalence in the world. She began studying the disease as an undergraduate at Sherbrooke University in Quebec and is now co-mentored by Professor Élise Duchesne from Laval University. 

Légaré is exploring the effects of weight training on individuals with myotonic dystrophy, focusing on molecular changes observed with training over time. Once believed to be ineffective or even harmful for DM patients, strength training is now recognized as beneficial—and Légaré’s work aims to uncover the science behind clinically observed improvements in patients.

The study, conducted at University of Quebec at Chicoutimi by Duchesne and colleagues, included 17 participants (nine men and eight women) between the ages of 25 and 60, who completed a prescribed 12-week training program that included two lift sessions per week.

“From our study, we know that weight training has been shown to benefit people living with DM,” said Légaré. “What we are trying to do now is identify the molecular changes happening in DM patients’ muscle cells as they build strength with targeted physical activity. Understanding these mechanisms could not only inform the development of new science-backed training regimens specially designed to benefit people living with DM, it could also point to new ways to monitor disease changes or progression.” 

In parallel, Légaré is studying how these molecular markers evolve over a longer time frame. By tracking changes in gene expression and RNA splicing in muscle cells of DM patients over a three-year period, Légaré aims to better understand broader patterns of disease progression.

The third prong of Légaré’s research is exploring the use of saliva samples to detect biomarkers that could reflect disease activity and treatment responses. If successful, this method could offer a simpler, more accessible way to monitor patients over time, without the need for invasive biopsy procedures. 

By pinpointing the molecular drivers of disease progression and the mechanisms behind therapeutic improvements, Légaré’s work could play a critical role in refining treatment strategies and enhancing patient care for the leading cause of muscular dystrophy.

Fighting Toxic RNAs with Flavonoids 

Subodh Mishra began working on neuromuscular diseases while undertaking his PhD research on non-coding RNA structures. He has since shifted focus to repeat expansion diseases, including myotonic dystrophy and ALS, which are caused by “toxic” RNAs and currently have no cures. 

In recent years, Mishra has been investigating quercetin, a “flavonoid” compound found naturally in a wide range of foods including apples, onions, tomatoes, grapes and broccoli. Quercetin is known to have anti-inflammatory properties, and Mishra’s earlier work has demonstrated that it shows promise as a way to treat adult-onset myotonic dystrophy. 

“In this new study, we are focusing on a modified form of the quercetin molecule that is more readily absorbed by the body,” said Mishra. “Our aim is to determine how we could use this compound as a potential treatment for myotonic dystrophy types 1 and 2, as well as a form of ALS linked to a specific type of repeat expansion.”

This work will focus on Enzymatically Modified Isoquercitrin (EMIQ), an FDA-approved nutritional supplement based on quercetin, looking closely at how the compound interacts with the toxic RNAs that cause repeat expansion diseases. By studying the mechanisms by which EMIQ reduces toxic RNA in cells, Mishra hopes to gain a deeper understanding of how the compound could be used alongside other existing or experimental treatments to improve outcomes for patients. 

“Through this project, we hope to uncover the precise mechanism by which EMIQ reduces toxic RNA levels associated with DM1, DM2 and c9ALS,” said Mishra. “While our earlier findings showed that EMIQ can significantly lower toxic RNA and rescue abnormal splicing patterns, we now aim to understand how it achieves this effect at the molecular level. 

“We also want to explore whether EMIQ works better alone or in combination with other treatments, such as splicing modulators or RNA-targeting compounds. Understanding these interactions could help us design effective multi-target strategies. Ultimately, we want to generate the kind of in-depth, mechanistic and preclinical data that can support future clinical development of EMIQ as a safe and effective therapeutic candidate for multiple repeat expansion diseases.”

Mishra and Berglund Lab colleagues are currently working with collaborators at Virginia Commonwealth University to pursue a clinical trial designed to test the use of EMIQ as a form of treatment for DM patients.