February 12, 2016
By Daniel J Wallace MD
The year 2016 opens with some very exciting new developments in the field of lupology. A few interesting examples are listed below.
It turns out that only 20% of lupus is due to a genetic component. Epigenetics, or how the environment influences the genome is very important. Recent studies, for example, have suggested lupus patients have a unique microbiome, or bacterial makeup in their gut. The ability to repair damaged DNA is by a process known as methylation. It is possible that certain foods ‘hypomethylate’ and these can make SLE worse, and other foods may be helpful which in turn affect T cell function, and thus inflammation.
Lupus in the kidney, or nephritis, has often been confusing to follow because of the lack of consistency in how we measure it. A group in Chicago has made the revolutionary finding that the prognosis of nephritis relates more to a structure in the kidney known as the interstitium as opposed to the glomerulous. This implies that way we have reading kidney biopsies for the last 30 years is wrong. Using newer forms of imaging and biomarkers, in the next 2-3 years, without performing serial biopsies, we should be able to assess and learn how to better manage lupus nephritis.
The failure of several large Phase III trials has been the result of inadequate study design rather than the failure of the drug to work. For example, agents known to be useful for the disease such as mycophenolate (Cell Cept) and rituximab failed in several studies. Several groups are now looking at different primary end points, or outcomes which make more sense, based on data from double blind studies to find out which type of testing does work. Also a group working with the newly formed Lupus Research Alliance, is studying repurposing, or using drugs already on the market for other diseases and known to be safe, for SLE. The first patients are going to be enrolled in the next few months.
Finally, new FDA guidelines for developing lupus drugs may appear in the next year. This will accelerate the development of new drugs and several new classes of agents, such as small molecules, anti-cytokine therapies and toleragens will be tested.