Researchers from Shinshu University have discovered DNA strands from lactic acid bacteria genome that are capable of promoting muscle cell differentiation to prevent loss of skeletal muscle mass, potentially paving the way for new nucleic acid drugs to treat muscle diseases.
To sit, to walk, and even to breathe, we rely on our muscles. But for some, performing these minor actions is a luxury, having lost the strength in their muscles to age and more often to disease. This condition, known as muscle atrophy, refers to the loss of muscle mass due to weakening and shrinking muscles. It may be caused by medical conditions such as amyotrophic lateral sclerosis (ALS), muscular dystrophy and multiple sclerosis. However, loss of muscle mass is also associated with other diseases like diabetes, cancer and heart failure.
For some diabetic patients, muscle wasting occurs and is found to be linked to increased mortality. One underlying cause for muscle wasting is suspected to be the reduced differentiation of myoblasts, which are the muscle precursor cells, into skeletal muscle cells.
With this knowledge, many scientists have embarked on investigations in search of ways to stimulate myoblast differentiation and so, improve skeletal muscle cell growth. Finally, a band of researchers from Shinshu University found that a specific DNA sequence derived from lactic acid bacteria demonstrates the ability to encourage myoblasts to differentiate into skeletal muscles by binding to a target protein in myoblasts, called nucleolin. Assistant Professor Tomohide Takaya reported that this “muscle-forming oligo DNA” (myoDN) can be manipulated to develop nucleic acid drugs to treat several muscle diseases.
During their investigation, they gathered myoblasts from healthy individuals, patients with type 1 diabetes and those with type 2 diabetes. They compared these myoblasts and confirmed that diabetic myoblasts had diminished potential to differentiate into skeletal muscle. To assess whether myoDN can stimulate myoblast differentiation, they administered myoDN and discovered that skeletal muscle differentiation was starkly improved. Additionally, myoDN was observed to have successfully suppressed the inflammatory responses induced by myoblasts in response to high concentrations of glucose and fatty acids found in the bloodstream of diabetic patients.
While myoDN has demonstrated promising potential to stimulate skeletal muscle differentiation in healthy and diabetic subjects alike, its effects were reportedly non-uniform and several individual differences were spotted. Consequently, clinical trials and other related tests need to be expanded to clarify doubts and validate its use for clinical applications.
To date, researchers have yet to deliver potent therapeutics to treat muscle wasting due to the sheer complexity of possible underlying mechanisms and links to other diseases. As such, researchers are hoping to validate the effectiveness of myoDN as a potential drug to prevent, treat, or reverse the loss of skeletal muscle mass.
Source: Nakamura et al. (2021). Myogenetic oligodeoxynucleotide (myoDN) recovers the differentiation of skeletal muscle myoblasts deteriorated by diabetes mellitus. Frontiers in Physiology, 12, 761.