Mycolic acids are distinctive components of the cell wall of Mycobacterium tuberculosis, which causes TB. A single intratracheal application of mycolic acids to allergen-sensitized mice prevented induced airway inflammation and promoted tolerance to repetitive allergen exposures. The persistent effect of the single treatment suggests a novel type of therapeutic compound that, by activating inherent immune regulatory mechanisms rather than blocking the consequences of inappropriate immune responses, promises a disease-modifying treatment of asthma.
The natural mycolic acids, generally containing around ninety carbons, are complex mixtures of different sub-classes and chain lengths and are very difficult to separate. We have shown that we can synthesise individual components and that some of these show even more marked effects in preliminary studies than the natural mixtures, while lacking unwanted side-effects. Individual synthetic MAs of the major methoxy-, alpha- and keto-MA sub-classes prone to foam cell induction but not inflammation induction (alpha- and keto-MA) exerted a tolerogenic function, thus providing proof-of principal for the segregation of inflammatory side-effects from sought after tolerogenic functionality.
This programme will systematically examine the structural features of synthetic mycolic acids and simpler analogues that are required for maximum therapeutic effect. It is hoped that this will not only lead to a fundamental understanding of the nature of the interaction of mycolic acids with molecular targets susceptible for immunomodulation but also to the identification of potential new and more effective therapies.