A study from the University of Illinois at Urbana-Champaign has determined how muscular dystrophy type 1, the most common form of adult muscular dystrophy, affects liver function, which provides a target for better therapies. Myotonic dystrophy type 1 (DM1) has historically been considered a muscular disease, but it is a systemic disorder that involves multiple organ systems, and one of the most important, but least studied of these is the liver. The findings were published in the journal Nature Communications.
The research team, led by Professor Auinash Kalsotra, developed a mouse model that simulates the liver symptoms of DM1, shedding light on why patients with this condition are prone to fatty liver disease and show unusual sensitivity to medications. DM1 is due to a mutation in the DMPK gene, which causes a CTG sequence to be repeated hundreds of times, thus producing toxic RNA which in turn disrupts cellular processes.
Although previous research centered on the muscular symptoms, this model goes directly for the liver symptoms, a smart maneuver considering drugs are first metabolized by the liver.
Kalsotra stressed that the liver-specific effects must be understood because of the liver’s role in drug metabolism.
“Most research has centered on muscle, but our findings indicate that new drugs should be tested for liver toxicity first,” Kalsotra explained.
Graduate student Zachary Dewald led the development of a line of mice with DM1-related toxic RNA solely in liver cells. The mice displayed both fatty liver and drug hypersensitivity, mirroring the challenges faced by human DM1 patients. In particular, these mice were highly sensitive to drugs, which researchers previously assumed to be muscle-related.
They found that the gene ACC-1, which controls fat synthesis, was improperly regulated in the diseased livers, causing fat accumulation. By treating the mice with ACC-1 inhibitors and correctors for splicing errors, they observed a significant reduction in liver fat accumulation within just 10 days. This suggests possible therapeutic strategies for controlling fatty liver in DM1 patients.
To verify that the liver alone was responsible for these phenotypes, the researchers compared their liver-specific mice to a second group of mice which expressed the mutation solely in muscle tissue. The fact that only the liver-targeted mice demonstrated fatty liver and drug sensitivity supports the unique contribution of liver dysfunction to DM1.
Kalsotra’s team is now looking to work with clinicians to examine liver tissue from DM1 patients and determine if human liver pathology matches what they found in mice. This study underscores the importance of focusing on individual organs in understanding and treating multisystemic diseases like muscular dystrophy.
Resources on Muscular Dystrophy and Liver Disease
Muscular Dystrophy and Liver Disease
Key Medical Databases
- NCBI PubMed: Comprehensive biomedical literature on muscular dystrophy and liver disease, including recent studies and advancements.
Visit PubMed - ClinicalTrials.gov: Registry of global clinical studies investigating treatments and therapies for muscular dystrophy and related liver complications.
Visit ClinicalTrials.gov
Liver Involvement in Muscular Dystrophy
Organ-Specific Research
- The Role of Liver in Muscular Dystrophy: An article on PubMed exploring the connection between liver dysfunction and muscle disease.
Read Article
Muscular Dystrophy Type 1 (DM1) Liver Symptoms
Specific Symptoms and Case Studies
- Abnormal Liver Function Tests in a Patient with Myotonic Dystrophy Type 1: Case report highlighting liver abnormalities in a DM1 patient.
View Case Report
