How Professor Fabienne Mackay is leading the global fight against Lupus

We speak with Prof Mackay for World Lupus Day about what’s next after her work in discovering the first Lupus treatment in more than 50 years.

Lupus is a severe syndrome effecting more than five million people worldwide. Most are women; but men can carry the burden of more severe symptoms.

It starts during the 20s and 30s, however symptoms are lifelong and worsen during ‘flare events’.

The work of Professor Fabienne Mackay, Head of the School of Biomedical Sciences, led to the development of the first new treatment for Lupus in more than 50 years.

The pharmaceutical therapy, approved in 2013, works by inhibiting B cell activating factor (BAFF). While BAFF is essential to a healthy immune system, abnormally high production has been linked with the development of Lupus and other autoimmune diseases.

This recent therapy is much safer than previous approaches, which inhibited B lymphocytes more generally and led to the severe side effects of suppressed immunity and high incidence of opportunistic infections.

Here’s what Professor Mackay and her laboratory are working on now in their quest to develop further strategies to target these molecules, and provide safer therapies for a broader range of Lupus patients.

Lupus affects five million people worldwide; can you briefly explain it?

An autoimmune disease, Lupus causes the body to produce antibodies that attack the body’s own tissue, leading to damage, pain and inflammation. Its exact cause remains unknown.

What’s new in your fight against Lupus?

Most treatments for Lupus are either toxic and/or compromising of the immune system. We are developing new therapeutic strategies that are effective at stopping Lupus in experimental animal models without compromising vital immunity needed to fight infections.

What challenges are you facing?

Another challenge with Lupus is that it is not one disease, but a set of syndromes. Therefore, treatment works for some patients with Lupus heterogeneous but not others, and there’s no predictors allowing doctors to know which treatment to choose that might work best.

Dr William Figgett in my laboratory has used very sophisticated big data analysis of the DNA from many patients with Lupus and was able to stratify patients into distinct subgroups with different gene signature.

Whether some subgroups respond better to some treatments is the next step – potentially validating this stratification as a way to predict which treatment should be used with which type of patient.

How have you got to this point?

It has taken many years of research, a deep understanding of SLE pathology, global collaborations and acquisition of new techniques such as big data analysis.

Why are you passionate about sharing your knowledge on the chronic autoimmune disease?

Lupus is a very heterogeneous disease. As a result, decades of clinical trials have only yielded one new treatment over 50 years. This is Belimumab and my work on BAFF laid the foundation for the development of Belimumab. Belimumab only works in a subset of Lupus patients. Other patients are still struggling with very toxic treatments and life quality and expectancy remains suboptimal for Lupus patients.

Read more about Professor Mackay and her laboratory’s work on Pursuit.

Lupus and its burden on global human health

AUSTRALIA

  • Approximately 90 per cent of all cases of Lupus occur in women, although the disease may be more severe when it occurs in males.
  • The highest incidence is among women of childbearing age.
  • Incidence, prevalence and severity of SLE are generally greater among non-white populations around the world in particular Indigenous Australian in Australia, as well as among those of lower socioeconomic status.

AMERICA

  • Based on a study of Medicaid data for 47 U.S. states plus Washington D.C., the prevalence of the disease in the United States was estimated to be 143.7 per 100,000.
  • The rate was six-fold higher among women and was nearly twice as high in women of African American as compared to white descent.
  • The incidence of SLE was 23.2 per 100,000 person-years for the period 2000-2004. The rate among black women was 196.2 per 100,000.

CANADA

  • According to Lupus Canada, one in 1,000 people in that country are living with Lupus.
  • Among members of the First Nations (Indigenous) populations of Canada, the overall prevalence of lupus in 1994-2007 was 27.3 per 10,000 females and 3.2 per 10,000 males.

EUROPE

  • According to Lupus Europe (website consulted April 27, 2017), one in 750 women in Europe suffer from SLE.
  • The incidence of Lupus in white European women is one in 1,000, whereas the rate in black European women is one in 250.
  • The overall prevalence of SLE in Norway (1999-2008) is 51.8 per 100,000 population and the mean annual incidence is 3.0 per 100,000.
  • The highest rate was detected in individuals of non-European descent, including foreign adoptions. The prevalence of SLE in Sweden ranges from 46 to 85 per 100,000 population.
  • The incidence of lupus in Germany for the year 2002 was estimated to be 1.9 per 100,000 person-years in women and 0.9 per 100,000 in men.
  • A study of the French national health data shows that the crude prevalence rate in that country in 2010 was 42.4 cases per 100,000 population (age-standardised prevalence according to WHO reference population 40.8 per 100,000).

ASIA

  • The average prevalence of Lupus in Asian countries is in the range of 30-50 per 100,000 population.
  • In a large population-based epidemiology study conducted in China, the prevalence of systemic lupus erythematosus in that country was estimated to be 0.03%.
  • An increase in awareness of the milder forms of SLE in recent years has led to an increase in reported cases worldwide.
  • As a result of patients being diagnosed at an earlier, milder stage of the disease, survival has improved, although quality-of-life measures such as fatigue may not have improved to the same extent (D'Cruz, D.P. et al (2007); Gabriel, S.E. et al (2009)).

For more epidemiology information, consult the Incidence and Prevalence Database (IPD): IPD: Systemic lupus erythematosus (SLE).

More information on World Lupus Day here.