Potential Applications of Molecular Biology to Leprosy Research
Dr. T. Gillis
Much debate over the last few years has centered on whether basic research should be encouraged in light of recent trends in prevalence rates for leprosy. Strategic planning by the WHO has indicated that they will direct their research initiatives toward applied research, primarily to field operations. While operational research is needed to focus our current knowledge in this disease, fundamental research must continue as a means of providing enhanced understanding of leprosy, with our ultimate goal being global eradication of leprosy. At a minimum we need a much fuller understanding of the mechanisms of protective immunity, the mechanisms associated with nerve damage and the epidemiology associated with spread of disease and risk of infection.
Neurologic aspects of leprosy. Nearly one-third of patients with leprosy develop disabilities as a result of nerve damage. MDT does not guarantee absence of nerve damage and attendant sensorimotor loss. We are still without a comprehensive model for pathogenesis of nerve damage.
Recent work by Rambukkana, and colleagues has opened a door in this area. Their work describes the probable nature of the neural tropism of M. leprae focusing on the molecular characteristics of the leprosy bacillus and it's affinity for a specific form of laminin found on Schwann cell-axon units. The specific region of the laminin-2 isoform (G domain of the alpha-2 chain) appears to be responsible for M. leprae's unique and specific targeting of the Schwann cell. An interesting correlation raised by this finding is that this form of laminin is restricted to the basal lamina of Schwann cells, striated muscle and the trophoblast of the placenta. These tissues have long been recognized as sites where M. leprae can be found in tissues apart from professional phagocytic cells, such as macrophages.
Molecular immunology of leprosy. With our improved understanding of what constitutes the lesion in its final stages, it would seem prudent that we need to begin investigating "early lesions" to describe molecular events which precede and possibly direct the outcome of disease including type I and type 2 reactions.
Leprosy vaccines. An ideal leprosy vaccine should be administered once and induce sustained protective immunity from early childhood through young adulthood. Studies are needed to exploit breakthroughs in vaccine development such as; evaluating protein subunit vaccines, so-called "Naked" DNA vaccines or redesigned BCG using recombinant DNA techniques.
"Naked" DNA vaccines are comprised of a specially designed bacterial plasmid carrying a bacterial gene which when injected into eukaryotic cells allows expression of the bacterial protein antigen. Expression of the bacterial antigen then gives rise to an immune response in the vaccinated host. The initial success of this approach was very much a surprise to the vaccine field, but the approach is gaining general acceptance as a potential alternative to vaccination under certain circumstances.
