Treating lupus by targeting T-cells
Finalist for the European Inventor Award 2017
Lupus is an incurable disease in which the immune system - tasked with defending the body from outside threats - turns inwards, attacking healthy tissues and processes. Until now, treatments have consisted of steroids, associated with significant side-effects when used over the long term, and so-called immunosuppressants that suppress the entire immune system and leave the body vulnerable to infection. Muller's new medication, marketed as Lupuzor and expected to be launched in 2018, silences only so-called "T-cells" associated with lupus while leaving healthy defences intact. Muller and her team at CNRS achieved their breakthrough in the early 2000s as they were researching the effects of synthetic peptides on immune responses. A peptide (a short chain of amino acids) known as P140 showed promising characteristics: instead of acting as an immunosuppressant, it acted as an immunomodulator, modifying the body's immune response to stop lupus in its tracks. Research showed that the peptide shut down the process of cell autophagy (from a Greek word meaning "self-devouring") that is behind lupus.
SLE affects 5 million people worldwide, 90% of whom are women. The prevalence of a symptomatic version of the disease ranges between 40 and 70 per 100 000 people around the world. The Latin name lupus means "wolf", as it resembles a wolf bite and reddens the skin of those affected with the disease. Symptoms such as fatigue, joint pain and hair loss prevent many patients from leading functional lives. And while 80-90% of those diagnosed with SLE have the same lifespan as those living without the disease, SLE can overwhelm the body with organ failure or large-scale infections and reduce longevity.
Untreated, SLE can have detrimental effects on muscles and bones, blood (anaemia) and the heart, lungs and kidneys. Yet it is estimated that over 60% of lupus patients do not receive adequate treatment. That's because lupus is extremely difficult to diagnose, since symptoms vary from patient to patient, and has until now been impossible to target with universal treatments. Muller's invention introduces a significant improvement. In the bigger picture, the mechanism behind her invention could be leveraged in drugs against other diseases, both autoimmune and non-autoimmune.
Muller has co-founded two companies based on her discoveries: Neosystem (now Polypeptide France) in 1986 and ImmuPharma in 2002. The inventor credits a close co-operation with researcher Robert Zimmer, currently President of ImmuPharma, with the successful transition from patented invention to a viable pharmaceutical company. A co-founder of ImmuPharma, Zimmer earned his MD at Strasbourg Medical School and a PhD at the University of Aix-Marseille, and he worked on drug development at companies such as Roche.
Marketed by ImmuPharma, Lupuzor (also known as Rigerimod, IPP-201101 and P140) is slated to launch in the US and five EU countries in 2018. Muller's breakthrough is heralded as a potential blockbuster drug for treating SLE. Based on revenues from current lupus medicines on the market, ImmuPharma conservatively estimates annual sales of Lupuzor could reach over EUR 940 million. The US market, where the drug is currently fast-tracked for FDA approval, is expected to contribute 80% of sales. The latest industry forecasts by GlobalData estimate that revenues from drugs to treat SLE and lupus nephritis (LN) - inflammation of the kidneys caused by SLE - in the world's seven largest pharmaceutical markets will reach EUR 3 billion by 2025.
How it works
Sylviane Muller's lupus treatment is based on a synthetically produced peptide. Previous immunosuppressant drugs functioned by suppressing over-stimulated "B-cells", key activators of large parts of the body's immune responses. In a completely new departure, Muller's P140 peptide takes action further upstream in the immune response. It specifically shuts down so-called CD4 T-cells before they can aggravate the B-cells that cause lupus.
This targeted approach marks a paradigm shift in treating autoimmune disease. Instead of shutting down otherwise healthy immune responses, Muller's discovery suppresses the T-cells, leaving the immune system modified but intact.
Sylviane Muller earned her doctorate in sciences at the University of Strasbourg and focused on immune responses as a postdoctoral researcher at the Max Planck Institute for Immunobiology in Freiburg. Today, Muller is a research director at CNRS and supervises over 50 researchers at the CNRS Laboratory of Therapeutic Immunology and Chemistry at the Institute of Molecular and Cellular Biology in Strasbourg, which she has headed since 2001. She is also Head and Coordinator of the Drug Discovery Center for Cancer and Inflammation. Her expertise in peptide immunochemistry, combined with insights into the molecular and cellular pathways behind autoimmune disease, led to the discovery of Lupuzor.
Muller has filed for 24 patents - 16 at the EPO - and published more than 330 papers and reviews.
For her contributions to the treatment and understanding of immune-inflammatory diseases, Muller has received numerous awards, including the Apollo-B award from Roche (2007), the CNRS Silver Medal (2010), the CNRS Innovation Medal (2015) and the French Académie des Sciences Grand Prix Léon Velluz (2016). The company she co-founded to market Lupuzor, ImmuPharma, was named Best Specialist Pharmaceutical Development Company (2017) by Global Health and Pharma magazine.
Did you know?
Of patents granted by the EPO, around 11-15% are awarded to women. Nevertheless, female inventors have been a force to reckon with at the European Inventor Award over the years.
If Sylviane Muller wins top honours in the Research category this year, she will join previous female honourees including Catia Bastioli (SMEs, 2007), Ann Lambrecht (Industry, 2011), Christine Van Broeckhoven (Research, 2011), Laura van 't Veer (SMEs, 2015) and Helen Lee (Popular Prize, 2016).
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