Why Is BuChE Important?

Butyrylcholinesterase (BuChE) is a naturally occurring protein found in minute quantities in human blood, at around 2mg/litre. The protein acts as a natural bio-scavenger, absorbing and degrading poisons, such as nerve agents, before they cause neurological damage.

Multiple efficacy studies, using a broad spectrum of live nerve agents, demonstrate that recombinant butyrylcholinesterase (rBuChE) is a potent bio-scavenger of nerve agents and can act as both a prophylactic as well as a post-exposure therapeutic.

The opportunity for rBuChE

Both the US Department of Defense (DoD) and the civilian Health and Human Services (HHS) have requirements for a broad spectrum pre- and post-exposure prophylaxis for nerve agents. The current DoD policy requires full force protection, so the stockpile would need to be sufficient to protect all of the branches of the military, as well as civilian first-responders.

The challenge

Approaches to utilising cross-species sources or recombinant technologies, including bacterial and expression through goat’s milk, have been met with a multitude of problems. Immunological issues and low functional efficacy are inhibiting the production of sufficient quantities for use in an emergency.

iosBio’s approach

iosBio is developing a novel recombinant form of human BuChE, which is being developed as a pre- and post-exposure therapy following exposure to susceptible agents.

We are in the unique position of being able to deliver reproducible doses of infectious, non-replicating viral vectors to the luminal surface of the intestinal mucosa. Once the epithelial lining cells are infected, they can produce proteins such as rBuCHE. These proteins can accumulate in the blood and can be expressed for several days, with the option to administer further doses of the vector to extend the protein expression.

Benefits

  • Transient vector-production of enzyme via gastrointestinal (GI) cells within the GI tract
  • Systemic availability of enzyme