The challenge of finding more effective treatments for lupus-according to Dr. Fabienne Mackay, PhD-lies in the nature of the disease itself. “Lupus is not one disease, but rather a set of syndromes in which no one treatment will work for all,” she explains.
With the objective to develop treatments that target the underlying disease pathways in individual patients, Dr. Mackay and her team are developing an approach that packs a 1-2 punch.
They are investigating whether the removal of harmful immune cells, combined with changes in diet, can alter the gut microbiome—thereby reducing immune system attacks.
Why focus on changes in the gut microbiome?
The link between bacterial imbalances and other immune-related diseases—most notably inflammatory bowel disease—has already been established. So, there is clear logic to look for similar imbalances in lupus-including such life-threatening consequences as lupus nephritis.
Describing herself as “long intrigued by the microbiota,” Dr. Mackay explained, “There is growing evidence of patients with lupus presenting with leaky gut syndrome. This leakage may trigger inflammation—and injury—as microbial matter enters the bloodstream as a pathogen.”
Leaky gut may, in some instances, play a critical role in lupus nephritis—a condition that occurs when lupus autoantibodies attack the kidneys—leading to impaired kidney function or failure.
Lupus nephritis is just one of the many manifestations of the disease that Dr. Mackay hopes to address. She and her collaborators have found, for example, that certain high-fiber diets protect mice both from lupus and from Type 1 diabetes. Both are diseases in which the immune system attacks itself. But with the right diet, she has found that the levels of circulating autoantibodies can be vastly reduced.
“Based on this knowledge,” Dr. Mackay says, “we aim to explore the effects of various diets on lupus, including the High Amylose Maize Starch diets that have been effective in our team member, Professor Charles Mackay’s study ofType 1 diabetes.”
As promising as this dietary approach may be, Dr. Mackay cautions that treatment by diets alone may not be enough. Undertaking a second line of inquiry, she is testing an approach that involves first depleting key pathogenic immune cells. This is followed with diets that are bacterial metabolite interventions.
If Dr. Mackay’s one-two approach is on the right track, she may have found a way to correct autoimmunity and restore normal immunological tolerance in lupus patients.
Moving forward, Dr. Mackay will investigate whether high-fiber diets actually create positive changes in the metabolites-and set in motion biological processes with healing properties.
“If we can successfully harness this kind of knowledge, we can develop treatment with surgical precision- rather than simply hoping that diet will work for every patient,” Dr. Mackay summarized her work.
Dr. Mackay is one of the most distinguished figures in the world of lupus research-but she would be the first to say that research is only one part of the equation.
“The grant from the LRA has given us the support we need to design and carry out thorough research studies. We wouldn’t have the resources to undertake this work without the LRA,” says Dr. Mackay. ‘And I’m truly grateful because research-like mine and the other investigations that this great organization funds-must go on!”
Dr. Mackay’s groundbreaking earlier work in gene function will greatly aid the new LRA-funded initiative.
This giant in the field of lupus research played a pivotal role in the development of the first new drug for lupus in over 60 years, and the first to show that the overproduction of BAFF (B-cell activating factor) is a driving factor in lupus.
