Cholesterol Metabolism Could Be DMD Therapeutic Target

According to Muscular Dystrophy News, new research suggests that the cholesterol metabolic pathway could offer a potential therapeutic target for patients with Duchenne muscular dystrophy (DMD). Following microRNA analysis, researchers determined that DMD could manifest in muscle-impacting metabolic changes. Since patients’ blood highlights cholesterol metabolism changes, targeting this pathway could offer new and more focused therapeutic options. See the full study findings published in the Journal of Cachexia, Sarcopenia, and Muscle.

Duchenne Muscular Dystrophy (DMD)

DMD gene mutations cause Duchenne muscular dystrophy (DMD), a neuromuscular disorder condition characterized by progressive muscle weakness. Normally, the DMD gene encodes for the production of dystrophin, which strengthens and protects muscles. However, patients with DMD are unable to make dystrophin. As a result, muscles, including heart and respiratory muscles, weaken. Because DMD is inherited in an X-linked recessive pattern, it mostly affects males. A female with DMD is rare, occurring in only 1 in approximately 50 million births. Symptoms usually begin before 6 years old and many patients use mobility aids by their teenage years. Symptoms include:

  • Difficulty walking or moving positions
  • Frequent tripping and/or falling
  • Delayed motor development
  • Fatigue
  • Muscle weakness beginning in the lower extremities which later progresses to the rest of the body
  • Poor head control (in early childhood)
  • Enlarged calves and shrinking thigh muscles
  • Learning disabilities or intellectual impairment
  • Heart disease and respiratory failure (later stages)

Cholesterol Metabolism

In this study, researchers wanted to understand how DMD mutations also prompted certain metabolic changes, including those affecting muscle. To do so, researchers decided to profile and analyze microRNA (mRNA). mRNA plays a role in gene expression and protein production.

Previously, much mRNA research centered around DMD has utilized animal models or smaller patient populations. Within this study, however, researchers collected blood samples from 100 patients with DMD, as well as 123 controls. Trial participants were divided into three groups based on age: those between ages 4-8, 8-12, and 12-20. In terms of treatment, patients were either treatment-naive (had never previously been treated) or were treated using corticosteroids. While younger patients had more mobility, many patients in the higher age groups were unable to walk.


Altogether, researchers isolated RNA samples and selected 81 samples to sequence. Through this, they evaluated which mRNA levels were higher and lower than seen in the control group. Ultimately, findings included:

  • There were no significant mRNA differences between patients with DMD who were treated and those who were not treated. Additionally, mRNA was also not affected by Body Mass Index (BMI), a measure of body fat based on height and weight.
  • mRNA regulation varied between patients and controls in the 4-12 age range, but not in those in the 12-20 age range.
  • Patients within the 4-12 age range saw 65 higher, and 25 lower, mRNA levels compared to controls. These included dystrophin-related mRNA, DLK1-DIO3 mRNAs (related to muscle function), and heart-enriched cardio-mRNA.
  • In the end, researchers determined Let-7 and miR-320 mRNAs played a role in DMD. Normally, these mRNAs play a role in heart and skeletal muscle function.
  • SREBP-1 and SREBP-2 genes were impacted by DMD. Together, these genes play a role in the metabolism of cholesterol and other fatty acids. After analyzing skeletal muscles in mice models of DMD, researchers determined that both genes were unregulated in the mice muscles.
  • Researchers evaluated simvastatin in mice models of DMD. Ultimately, this treatment normalized and balanced both cholesterol production and SREBP gene expression.
  • Finally, researchers also noticed 2x more cholesterol in muscle samples from patients with DMD than from the control group.

Altogether, researchers determined that cholesterol metabolism is abnormal in patients with DMD. Thus, by addressing cholesterol metabolism, researchers could potentially address an unmet need within this patient community.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

Share this post

Share on facebook
Share on google
Share on twitter
Share on linkedin
Share on pinterest
Share on print
Share on email