Targeting Syt2 to Prevent Airway Mucin Hypersecretion
2022 Harrington Scholar-Innovator
Human lungs have a remarkable self-cleaning system. Polymeric mucins are secreted into the airway lumen to form mucus. The mucus is continuously propelled out of the lungs by the rhythmic sweeping of fine, hair-like cilia, taking with it inhaled particles and pathogens. This innate defense system typically protects the lungs very well, but dysfunction in it can contribute to serious diseases including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis.
“As long as you have the normal low level of mucin being slowly and steadily secreted, everything works fine,” Dr. Dickey explains. “But when the airway senses threats, one of its responses is to dramatically increase the production of mucin. A sudden, massive release of highly expressed mucin can overwhelm the airway's hydration capacity, creating excessively viscoelastic and adhesive mucus that results in airflow obstruction and lung inflammation.”
Some researchers are trying to control the excessive production of mucin, but Dr. Dickey and his team are taking another path and seeking to prevent its sudden release.
Dr. Dickey and his colleagues, along with structural biologist Axel Brunger of Stanford University, had previously identified the calcium sensor Synaptotagmin-2 (Syt-2) as the trigger for rapid mucin secretion. Now they have identified a stapled peptide that protects against airway obstruction by inhibiting Syt2 interaction with the airway epithelial cell secretory machinery. They propose developing this lead compound as an inhaled therapeutic for the treatment of muco-obstructive lung diseases.
With the help of their Harrington advisors, Dr. Dickey and his team are working to improve the molecule and give it optimal characteristics before going into clinical studies.
Unraveling the Secrets of Lung Health: Preventing Mucus-Related Diseases: Dr. Burton Dickey, MD Anderson Cancer Center, shares his research on preventing airway mucin hypersecretion, a crucial factor in lung diseases like asthma, COPD, and cystic fibrosis. Discover how innovative approaches, like inhibiting the calcium sensor Syt-2, can revolutionize the treatment of muco-obstructive lung diseases.