Lipoedema is a chronic disease of high unmet need. Challenges include lack of diagnostic tools and animal models, ignorance and prejudice, as well as getting international consensus due to limited research in this field. At the current global medical online hub (MOH) webinar “Latest insights in the lipoedema pathophysiology and potential new therapeutic pathways” on August 27, 2022, Drs Ramin Shayan, Tara Karnezis, and Stanley Rockson shared their cutting-edge research on this topic and discussed paradoxes and future perspectives associated with the disease.
Lipoedema, a chronic lymphatic microvascular disease with pathological accumulation of subcutaneous adipose tissue, is often misdiagnosed as obesity or lymphedema. “There is no group more desperate than patients with lipoedema”, moderator Dr Christine Moffatt, clinical professor of skin integrity and emeritus at Nottingham University Hospital in the UK opened the 8th online event of the global MOH series, which was co-moderated by Dr Sylvain Gaillard, corporate medical affairs manager at Sigvaris Group in Switzerland. The first speaker, Dr Ramin Shayan, specialist plastic and reconstructive surgeon and director of O’Brien Institute Department at St Vincent’s Institute in Fitzroy, Victoria, Australia, shared his view on lipoedema from the plastic surgeon’s perspective.
While current treatments are limited and non-curative, one of the aims of reconstructive surgery is to help heal the body. The overall goal is to enhance patient’s quality of life by treating stigmatisation, fat-shaming, self-esteem problems, emotional distress and depression. However, surgical methods are costly, time-consuming and not feasible for all patients. The key to unravelling lipoedema are biomarkers and a molecular mechanism that can be targeted. The research group employed a comprehensive ‘omics’ platform to analyse tissue across modalities in order to find the stem cells driving the disease.
Dr Tara Karnezis, lead of lipoedema Lab presented latest findings on the identification of Bub1, a mitotic checkpoint protein involved in unregulated cell growth, as a potential therapeutic avenue to target cancer stem cells. “Bub1 is critical for lipoedema stem cell growth, which in turn is more sensitive to Bub1 inhibition than normal fat,” Dr Karnezis summarised the rationale for focussing on Bub1. Future plans include validation of Bub1 as a biomarkerto design a novel Bub1 inhibitor and to expand this knowledge into obesity and other metabolic diseases.
In the second presentation Dr Stanley Rockson, cardiologist at Stanford University School of Medicine, unravelled the clinical problem of lipoedema and presented perspectives on how to move forward. The diagnosis is currently based on clinical grounds, although diagnostic evaluation may be necessary to distinguish from other systemic disorders with overlapping phenotypes. Treatment is directed toward relief of symptoms. Efficacy of treatment interventions has not been fully evaluated and is therefore not evidence-based. In the setting of unsuccessful conservative management, lymph-sparing liposuction for symptom palliation can be considered, however, evidence-based assessment of long-term efficacy is needed. Dr Rockson’s research group identified platelet factor 4 (PF4/CXCL4) as a biomarker that could be used to diagnose lymphatic vasculature dysfunction. Furthermore, they determined that PF4 levels in circulating blood plasma exosomes were also elevated in patients with lipoedema, supporting current claims arguing that at least some of the underlying attributes of this disease are also the consequence of lymphatic defects.
During the lively discussion, joined by panellists Drs Asmaa Alderaa (Saudi-Arabia), the experts stressed the need for biomarkers for the distinction of lipoedema from obesity in order to be able to reimburse patients. Furthermore, expectation management in the context of surgery is important and adjustable compression garments after surgery are recommended.