Lay Summary

Proposal No. IBD-0233
Principal Investigator:  Michael T. Collins, D.V.M., Ph.D.
Applicant Organization:  University of Wisconsin, Madison (U.S.A.)
Project Title:  Evidence-based selection of antibiotics for treatment of Crohn's disease
Period of Award:  January 1, 2008 – February 28, 2009

Scientists have recently concluded that people with CD are possibly infected with a bacterial agent that causes a similar disease in animals known as Johne’s disease or paratuberculosis.  This causative bacterial agent is related to the cause of tuberculosis and is named Mycobacterium avium subspecies paratuberculosis (abbreviated in this grant proposal as MAP).  A clear cut association has not been established between testing positive for MAP and having CD, and scientists have not concluded if MAP actually causes CD.  It is possible that MAP is a secondary problem.  Either way, the infection is clinically important and effective treatment of this infection could perhaps improve the health of people living with CD.

There have been some attempts to treat CD using anti-MAP therapy.  Some results have been dramatic: full remission of clinical signs for over two years!  Other results have not been as successful.  A possible explanation for the inconsistencies in anti-MAP treatment results is that little is known about which drugs or drug combinations are best for treatment of a MAP infection in humans.  Also, research has shown that some of the immunosuppressive drugs commonly taken by Crohn’s patients can interfere with the effectiveness of antibiotics against MAP.

Determining the best antibiotics is a multi-step process.  First, the drugs must be tested by directly exposing multiple human-origin strains of MAP to various concentrations of antibiotics in test tubes.  After a suitable exposure time, the numbers of surviving MAP bacteria are counted.  Drugs showing the most promise at killing or inhibiting MAP growth are then further tested.  The 2nd stage of drug testing involves use of MAP-infected human white blood cells called macrophages.  To be effective, antibiotics must both get inside cells where MAP live and also kill or inhibit MAP growth.  Drugs showing the most promise in stage #2 then graduate to animal testing, the 3rd testing stage.  Successful research in all three stages is necessary before humans can safely and reliably be treated with the most effective antibiotics for MAP infection.  This proposal is restricted to the 1st stage of drug testing, but it is hoped that with promising results, much larger sources of funding can be obtained to support the more laborious and expensive stage #2 and stage #3 testing.  Ultimately, this line of research could lead to more effective therapy for CD if MAP is a cause of many cases of CD as some researchers suggest.