Targeting microRNAs for treatment of Cystic Fibrosis
T2018-007 Autophagy is impaired in patients with Cystic Fibrosis, rendering them susceptible to microbial infections. Autophagy is negatively regulated by microRNAs, Mir17 and Mir20, and this anti-microRNA antagomir may be optimized as a novel therapeutic to treat Cystic Fibrosis patients.
Cystic fibrosis (CF) is a fatal genetic disorder affecting more than 30,000 people in the US and approximately 70,000 people worldwide (Cystic Fibrosis Foundation), making it the most common inherited lethal disease. CF patients are born with innate immune deficiency, rendering them prone to microbial infections, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cenocepacia. Accordingly, the leading cause of death among patients with CF is lung damage secondary to chronic infections. Notably, all three microbes are controlled by autophagy in healthy immune cells, however, this process is significantly impaired in CF patients. For this reason, the ability to therapeutically modulate autophagy with minimal side-effects is of great interest in order to improve CF patient outcomes following infection.
Researchers at The Ohio State University, led by Dr. Amal Amer, have developed technology that restores autophagy activity upon infection in CF patients. Dr. Amer identified two Mirs in the Mir17-92 cluster (specifically, MiR17 and Mir20a), which are elevated in CF mice and CF patients and are negative regulators of autophagy. This technology is comprised of antagomirs, which act as an antagonist for use in targeting Mir17 and Mir20 (Tazi et al, Autophagy, 2016 Nov;12(11):2026-2037). Targeting microRNAs is a promising strategy for the development of new therapeutics for improved treatment of the disease. By downregulating microRNA targets that are interfering with autophagy expression, normal autophagy processes can be completed, restoring normal host-defense function and treating CF.
- Cystic Fibrosis Therapeutics
- microRNA Therapeutics
- Improved outcomes for CF patients from the ability of this technology to restore autophagy activity
- Reduced side-effects compared to alternative treatments available on the market
- Increases effectiveness of currently available treatments