Engineered bacteria administered intranasally can propel molecules across the brain-blood barrier

In a fascinating and exciting article (Engineered commensals for targeted nose-to-brain drug delivery, Cell 188, 1545-1562) by a @NUS team led by @matthew wook chang, the authors:

• Identified lactic acid bacteria (Lactobacilus plantarum, or Lp) that could bind uniquely to the Olfactory Epithelium (OE);

• engineered Lp to secrete appetite-regulating hormones (leptin, alpha-MSH and BNDF);

• administered them to mice intranasally;

• and found that Lp was localized in the OE, and detected only in the intestine and kidneys for elimination, observed reduced body weight gain in an obesity mouse model compared to control;

• they also found that direct intranasal administration of the hormones had no effect, suggesting that Lp binding to the OE is a crucial step toward bypassing the blood-brain barrier (BBB): payloads pass across the OE to the olfactory bulb and then to other brain regions.

Why is this exciting? The BBB is one of the biggest obstacles to deliver drugs to the brain. Plus a lot of natural peptides and proteins, like leptin) have a short half-life in circulation. So the ability to deliver these products via a nasal spray could be a game changer.

Also, I love engineered commensals.