Medical research for lupus: towards less toxic treatments and personalised medicine
Published 15 Jul 2019 • Updated 1 Aug 2019 • By Louise Bollecker
Laurent Chiche is an internist at the Marseille European Hospital and a member of the Carenity scientific committee. He agreed to answer our questions about medical research in lupus, between difficulties, concrete advances and hope for new therapies.
Hello Laurent, thank you for agreeing to answer our questions. What are your current research topics on lupus?
I conduct two types of research: first, research with industrial partners to enable patients to participate in clinical trials and to test new molecules that target the immune system. This research has become increasingly important in recent years.
"Our research concerning microbiota is directly relevant to patients with lupus."
Then there is research specific to the centre in which I work, in other words, we seek to produce concrete applications based on fundamental knowledge. One focuses on the identification of biomarkers, including prognostic markers or markers of disease activity. Another focuses on new therapies such as fecal transplantation: first there is a phase to better understand the microbiota of patients; then, we hope to be able to intervene directly on the microbiota with probiotics (living microorganisms, most often bacteria), antibiotics and especially with fecal transplantation. As the immune system is involved in almost every disease in the world, our research on the microbiota therefore directly concerns patients with lupus but goes beyond this condition. These include Parkinson's, obesity, some infections and autoimmune diseases.
Editor's note: the intestinal flora or microbiota is the set of microorganisms (mainly bacteria) that colonise our digestive tract. Fecal microbiota transplantation consists in administering a preparation of faecal matter from a healthy subject to a patient suffering from a pathology related to an alteration of the intestinal microbiota, in order to exert therapeutic effects.
How far will this research lead to concrete advances for patients?
Lupus is one of the diseases for which we are very cautious. There have been many failures in the last ten years: Phase 2 clinical trials were very promising but Phase 3 proved to be very disappointing. That is why we must remain cautious in communicating scientific discoveries, because not all will lead to a new drug or a miracle solution for patients.
Editor's note: Clinical trials are conducted in several phases: a first phase usually consists of testing the drug in healthy volunteers; in phase 2, the drug is administered to a larger group of people, including patients. Phase 3 includes hundreds or even thousands of volunteers from different countries. The role of Phase 3 includes identifying potential contraindications and demonstrating the effectiveness of the new treatment compared to existing drugs.
What are the avenues being explored?
In terms of pathophysiology (study of disturbances in the normal functioning of the constituent elements of the human body, such as organs, editor's note), there are still many questions to be resolved. Twenty years ago, it was thought that the disease would be cured by drugs targeting interferon (a protein produced by immune system cells). This remains the most important signalling pathway involved in the disease, but patients are so different at the molecular level that there is probably not only one pathway to treat them. When you look at the symptoms of different patients, you realise that there is not just one lupus. At the molecular level, it is the same thing: patients do not have the same molecular characteristics and this must be taken into account.
"It is essential to make this leap to personalised medicine"
Unfortunately, we do not yet have personalised medicine for these patients. We have a lot to learn from oncology on this point, because it is essential to make this leap to personalised medicine. Efforts are currently being made to characterise patients at the molecular level, but ongoing clinical trials do not always make this effort before proposing a new treatment, leading to failures. Nevertheless, we are seeing the arrival of more subtle clinical trials, in smaller numbers.
Finally, as I mentioned above, beyond the direct manipulation of the immune system, the microbiota offers incredible opportunities.
What innovations can we hope for in the end?
Molecules, hopefully, will make it through the game. Highly targeted molecules have not worked so far, which is why we are currently studying more intracellular molecules, with more global civilizational pathways, that have a chance to replace old immunosuppressants. This will result in a long-term gain in toxicity.
"Every year, new drugs are tested."
Indeed, patients are mainly bothered by the toxicity of treatments (immunosuppressants or cortisone). It would already be a major step forward to have safer drugs for the patient. This would avoid major adverse reactions; it should be known that patients have significant mortality due to drugs while the disease is often well controlled. Osteoporosis related to the use of corticosteroids, overweight with cardiovascular manifestations or superinfections may occur.
Warning, it is better to take these drugs than not to treat the disease, because it would then take more serious forms, such as kidney damage, brain damage, etc.
(Re)read the first interview of Laurent Chiche:
And what do you think of your daily treatment? Had you heard about microbiota or personalised medicine?
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