Professor Fabienne Mackay's lupus research
Systemic Lupus Erythematosus (SLE), more commonly known as “Lupus”, is an autoimmune disease affecting many tissues and organs in the body. The normal role of our immune system is to detect and stop infections, or stop cancer cells by eliminating them before they grow into tumors.
However, for reasons that are still unclear, the immune system of lupus patients is confused and attacks normal tissues thinking they are foreign rather than part of the normal body.
The laboratory of Professor Fabienne Mackay has worked for many years on what causes Lupus. Her work discovered a factor named BAFF which in healthy individuals is produced in low quantities to help immune cells survive and make protective antibodies. However, in patients with Lupus, BAFF levels are abnormally high and this leads to the emergence of rogue Immune cells attacking healthy tissues such as the skin, kidneys and the brain. Over the years Professor Mackay's laboratory has dissected the mechanism used by BAFF to confuse the immune system and to drive disease. Inhibitors of this factor have been developed and were approved for clinical use in 2011. The resulting medicine, Belimumab, was the first new treatment for Lupus in over 50 years.
This latest development is a fantastic advance in Medicine and provides an additional treating options to lupus patients unable to respond to traditional older drugs, most of which are highly toxic and/or ineffective.
However, there are a number of lupus patients that do not respond to this new treatment. Moreover, most treatments for Lupus, including the new BAFF inhibitor, are strongly immuno-suppressive. Difficulty in treating patients with Lupus lies in the heterogeneity of this disease. Lupus is probably not just one disease and patients with Lupus can stratified into different subgroups depending on the set of symptoms they experience. However, this stratification does not help predict which treatments might work best. To address this issue, the laboratory of Professor Mackay is looking at the genome of patients with Lupus and using super-computing, her team is aiming to identify precise subgroups of patients with SLE and study how these subgroups respond to treatments. This will allow better prediction of treatments that are more likely to work in particular patients, a strategy otherwise called “precision medicine”.
Prof Mackay has also identified a new therapeutic target in Lupus which when inhibited prevents disease progression without compromising the immune system. As such a blocker of this new therapeutic target is likely to be safer and better tolerated by patients. Her group has developed a mouse model of Lupus expressing the human version of the therapeutic target and therapeutic antibodies blocking the human targets. Her laboratory is currently validating these antibodies against the human target in preclinical models of Lupus. The advantage of this approach is that it stops disease in many different models of Lupus, irrespective of the underlying mechanism driving disease, giving us hope that this strategy will work on many subtypes of patients with Lupus.
Finally, her laboratory is interested in the connection between diet and autoimmunity and has found that modification of the diet has a profound effect on autoantibody production suggesting that the gut microbiome plays an important role in driving autoimmune diseases such as Lupus. These new findings open very exciting possibilities for new treatments of Lupus.
Further information on World Lupus Day (May 10).