The EIC meet each year for a major conference over three days. This year’s event (9-11 Feb) was attended in full by our adviser Professor Rob Evans, who was joined on the last day for sessions focusing on iron overload by our Chief Executive David Head and Chairman Howard Don.
The three days of scientific meetings were followed, as in previous years, by a day allocated to the Annual General Meeting of EFAPH members. EFAPH brings together patient organisations from across the continent to share their ideas on work to support patients and raise awareness of iron overload. Below is a summary from the last scientific day, a report from the EFAPH meeting day is at http://haemochromatosis.org.uk/zurich-2018-day-2.
EIC Day 3 Saturday 10 February 2018
Presentations from EIC scientists were broken into a number of sessions during the day. THS representatives attended presentations most relevant to the society’s work including interesting lectures on the impact of iron in the brain and of iron in the liver.
The first presentation of the day was from Dr Raffaella Gozzelino, a scientist working at the Chronic Diseases Research Centre in Lisbon. Dr Gozzelino reported work at the centre which has demonstrated that increased levels of iron stored in the brains of laboratory mice seems to accelerate the effects of aging by making the brain cells susceptible to inflammation. In turn this appears to lead to a loss of locomotion function, a measure that indicates symptoms of Parkinson’s disease. Further experimentation has demonstrated that the use of Deferiprone, a chelating drug, in iron-overloaded mice, appears to mitigate this effect. All of this is very preliminary, but further tests are ongoing and are of interest to the society for obvious reasons; we will be watching Dr Gozzelino’s work of course.
The meeting then heard from Dr Charareh Pourzand from The University of Bath, who spoke about the impact of iron on the skin. Dr Pourzand is working on a theory that iron in certain skin cells makes them more susceptible to damage by UVA light. as we know that iron overloaded patients often suffer with a wide range of skin conditions, this would appear to be supported anecdotally.
Just before the coffee break Dr Carole Peyssonnaux from Institut Cochin in Paris gave an excellent talk on the role of hepcidin. As research progresses it is becoming evident that hepcidin, which is known to control iron homeostasis (iron metabolism balance), has a more complex role in the body than was previously understood. In particular she explored its dual roles of managing iron and controlling the immune system, particularly with respect to the skin once again.
After the coffee break the focus of the meeting turned to the liver, with Professor Pietrangelo of the University of Modena in Italy setting the scene by outlining the latest thinking and research into to role of the liver and the impact of stored iron on the organ.
This really underscored to us just how skilled and talented the scientists working on iron metabolism are. Professor Pietrangelo provided a time line of all the discoveries and advances over the years which opened our eyes to the amount of work and progress that has been made in understanding our bodies. Recent advances in the understanding of genetics and in research technologies are adding to this knowledge at an incredible rate and there is little doubt that we owe the scientists studying GH a great deal.
Over the course of the session several papers were presented. Particularly worthy of mention was a presentation entitled Oral ferroportin inhibitor prevents iron overload in the HFE C282Y mouse model of hereditary hemochromatosis presented by Dr Naja Nyffenegger of Vifor Pharmaceuticals based in St Gallen, Switzerland.
As the title implies, Dr Nyffenegger has established that in mice it is possible to prevent iron overload by using inhibitors introduced orally. There are plans to progress to clinical trials in humans (Phase 1) during 2018 which is very exciting, but it must be stressed that a Phase 1 trial is the very earliest stage, aimed at proving safety, and that even if successful the process of bringing a treatment to market can take several phases of study over many years.
Just before lunch Professor Gary Brittenham of Colombia University spoke about the use of stable isolated isotypes of iron to measure rates of iron absorption and passage. This facilitates highly accurate measurement, which is important for researchers working on both iron overload and iron deficiency. However, our non-scientific representatives at the meeting did observe that “some slides are less easy to interpret than others ….”.
Much of the afternoon was subsequently given over to presentations about iron deficiency anaemia, before returning to issues more relevant to our work when Dr Houda Hamdi-Roze from The University of Rennes, France discussed the application of next generation sequencing in genetic analysis. Next generation sequencing technology is a means of sequencing whole genes or parts of genes in parallel rather than looking for specific mutations one at a time. The technology is highly efficient and increasingly accessible. The gene panels examined with the technology can include all those genes known to affect iron metabolism, not just HFE. Next generation sequencing is more expensive than the basic C282Y test but is cheaper than sequencing genes individually. For researchers, the breadth of the genes being sequenced has also allowed the identification of novel (newly identified) mutations in genes that would not normally have been considered as having a role in haemochromatosis and has revealed that digenic inheritance of haemochromatosis is more common than was originally thought.
Further presentations included:
- A study of the impact of single nucleotide polymorphisms in NRF2, a transcription factor that regulates the expression of antioxidant genes, in haemochromatosis patients with HFE mutations. Scientists at the University of Porto are investigating whether faults in NRF2 might account for the level of penetrance of iron overload in people with HFE mutations, alongside environmental or possible further genetic factors.
- An interesting study of the effect of de-ironing on livers damaged by fibrosis, conducted at University hospital in Rennes, France. This study has shown that in a study of 85 patients, in 79% of cases liver fibrosis regressed by 1 or 2 points on the standard four point scale of damage. Quantifying the improvement in liver condition possible through de-ironing is important as we work to develop and/or advocate consistent and evidence-based patient pathways.
- An investigation into haemochromatosis arthropathy, again at the University of Porto, looking at the impact of iron-induced cartilage degradation. Currently although there is no doubt about the link between iron overload and joint disease, the exact machanism by which the damage is done are not fully understood, so we are pleased to see that investigations of this type are underway.
The above is a summary from the last scientific day of the EIC meeting 2018, a report from the subsequent EFAPH meeting is at http://haemochromatosis.org.uk/zurich-2018-day-2.