Repairing the Heart with Bacteria?

The delivery of genes or proteins to the damaged area in the heart following a heart attack is an important area of research. The aim is to quickly accumulate therapeutic molecules, such as proteins and genes, selectively within the myocardium area of the heart that has been affected by reduced blood flow (the ischemic myocardium). This is done in order to prevent further death of cells in the heart and improve function of the heart. To date, no vectors available to researchers have the necessary properties to allow selective delivery to this area following injection into the bloodstream.

In cancer therapy, many researchers have exploited the fact that many solid cancers possess hypoxic regions, that is, regions of the tumour that are poorly oxygenated. One such agent that can target these regions is a defective form of the bacteria S. typhimurium. In the May 2011 issue of Molecular Therapy, Dr. Uyenchi Le and colleagues have asked whether this defective form of S. typimurium can also target to the damaged heart.

In a series of very elegant scientific experiments, the researchers used an engineered form of the bacteria that could be easily monitored by non-invasive imaging techniques. They were able to assess the targeting of the bacteria to the heart following injection into animals that had or had not been subjected to a procedure that reproduced the heart attack scenario (via ligation of one of the arteries in the heart). Indeed, the results presented show efficient selective uptake into the damaged myocardium with colonization by the bacteria lasting several days. Using bacteria in this setting might suggest that some toxicity from injection of the bacteria might also arise, potentially limiting the use of this agent. However, the researchers used a series of assays for “biomarkers” of inflammation and showed no consequence of bacterial injection, either in the heart or in the systemic circulation.

Many questions still remain, including understanding why accumulation occurs in the damaged heart and whether this delivery system can provide improved outcome following a heart attack by delivery of a therapeutic agent. Future studies are therefore eagerly awaited.