Technology

History

In 1966 Dr L M McEwen recognized that the desensitising effect of a low dose of allergen could be potentiated by adding beta glucuronidase.  In a series of studies at St Mary’s Hospital medical school he was able to discover the precise dose response parameters and optimize the method to arrive at a reliable form of allergy therapy.  Treatment is given in the form of single small intradermal injections.  A significant number of successful double blind trials have been conducted examining this method, christened Enzyme Potentiated Desensitisation or EPD for short.

Application to Autoimmune conditions

EPD was formulated to treat conditions caused by inappropriate immune reactions to harmless substances encountered in the environment – the field of allergies and intolerances.  Conventionally it is believed that the mechanisms underlying autoimmune disease are significantly different from those underlying (say) hay fever.  In addition the dose sensitivity of the treatment method did not seem to lend itself to situations in which the antigen, as a part of the body’s own makeup, might be present in uncontrollable quantities during treatment.  However, it appears that only modest adaptations can yield a successful result in models of autoimmune disease.

Safety

The doses of allergen required for EPD are very small - similar to or smaller than skin prick test amounts.  The dose of enzyme given is small in comparison to the quantity normally present in the body, comparable with the content of 1ml of blood plasma.  Therefore the method is generally extremely safe. The American EPD Society compiled adatabase of EPD use in the USunder the auspices of an Investigational Review Board.  In September 1999 5,400 patients in this study had received at least 3 doses of EPD.  No severe adverse reactions were reported.

Mechanism

T lymphocytes are cells which are the workhorses of the adaptive immune system.  The way these cells respond to an antigen is programmed by antigen-presenting dendritic cells which are particularly numerous in the dermis.  How the lymphocyte will respond to the antigen depends on what extra signals it receives from co-stimulatory ligands on the dendritic cell.  It can respond actively by production of antibodies, be passive (anergic) or it can act to down-regulate the immune response.  Once a T lymphocyte has received an antigen signal from a dendritic cell it migrates to the regional lymph nodes, maturing as it goes.  There it passes on the message either by reproducing itself or by encouraging the proliferation of cells that agree with it.

Chemicals called interleukins (ILs) are important messengers in the immune system.  IL10 is known to down-regulate T lymphocyte responses.  Studies have shown that IL10 is raised by EPD and that this increase persists. In one study IL10 levels remained raised after 15 days.  It is also notable that the positive therapeutic benefits of EPD treatment generally are not apparent until some weeks following an injection – consistent with the migration/maturation timetable of regulatory lymphocytes.

Production of regulatory T lymphocytes is therefore probably the chief effect of EPD.  The combination of a very low dose of antigen with beta glucuronidase placed intradermally conditions dendritic cells to present the antigen as something ‘harmless’ and therefore a substance to which tolerance should be encouraged.