Myotonic dystrophy is a progressive genetic disease that leads to muscle weakness, impaired mobility, fatigue, and heart complications. It’s caused by expanded nucleotide repeats in the DMPK gene, which lead to toxic RNA buildup inside cells. This toxic RNA traps an important protein called MBNL, disrupting the normal processing of muscle-related RNAs and resulting in faulty proteins.
To address this, researchers have designed therapeutic oligonucleotides – short strands of RNA-like molecules – that bind to the toxic DMPK RNA and signal it for destruction. Once cleared, MBNL is free again, allowing normal RNA processing to resume. This may help restore healthy muscle proteins and improve muscle function.
However, getting these oligonucleotides into muscle cells is a major challenge. Avidity Biosciences is tackling this with their Antibody-Oligonucleotide Conjugates (AOCs). These engineered molecules combine an antibody that targets muscle cells with a therapeutic oligo. Once the antibody binds to the cell, the entire AOC is taken up – delivering the therapeutic payload exactly where it’s needed.
In preclinical studies, AOCs showed strong effects with dosing as infrequent as once every three months. Clinical trials for treating myotonic dystrophy are underway, and Avidity is also exploring AOCs for other muscle diseases.
Learn more at www.aviditybiosciences.com
