THE Histiocytosis Research Trust's latest research project for 2011 will focus on LCH and improving diagnostic and prognostic tests as well as therapeutic targets.
The recipients of The Jon Pritchard Research Award are Professor Frederic Geissmann of King’s College, London and Professor Matthew Collin, of the Institute of Cellular Medicine at Newcastle University.
The duo’s project, entitled Cell Autonomous Mechanisms in the Pathogenesis of Langerhan’s Cell Histiocytosis, was selected from 12 applications received after the Trust invited calls for proposals last May.
Professor Collin explained: “We are delighted to receive this award. It will allow LCH research in the UK to take a unified stance against the disease with clinicians and scientists all working together. With LCH IV and the help of all the patients, we hope to be able to look at the cells and tissues of LCH in new ways, to explore exciting new ground related to the recent discovery of the V600E BRAF mutation in the majority of LCH cases.
“Our project aims to directly test the role of abnormal survival and proliferation in the development of LCH by a number of approaches. In particular, we will generate models to study the role of mutation of BRAF and we will investigate the existence of mutations in BRAF and in related cellular pathways in human patients. These studies are likely to lead to new diagnostic and prognostic tests and therapeutic targets for LCH.”
To date the causes of LCH and the mechanisms responsible for the disease are not well understood making the establishment of diagnostic and prognostic tests and the design of rational treatment extremely difficult.
However, after many years of searching for candidate genetic lesions in LCH, a recent breakthrough study has identified a mutation of the gene BRAF in over half of LCH samples. BRAF is a protein involved in cell activation, survival and proliferation and is mutated in numerous human cancers.
“This suggests that in the majority of patients, LCH is connected to a genetic defect within the cells themselves, although a complex of other factors may still play a role in LCH pathology particularly in patients who do not have a BRAF mutation,” added Professor Collin.
Those who applied for the Jon Pritchard Research Award were asked to set out the key objectives of their research and provide a brief description of the background, methods to be used and key references. They were also asked to describe the principal investigator and research facilities and indicate the source and availability of clinical samples if these were to be used.
Applications were scrutinised by the Trust’s Scientific Review board led by H R Trust Trustee Professor Peter Beverley and colleagues Professors Alain Fischer, Ron Jaffe, Hugh Perry and Ralph Steinman. They were also assessed by independent external reviewers. Candidates had to submit proposals linking basic and clinical science but the overriding consideration was scientific excellence.
The panel faced a difficult task in identifying the best projects as they were all of a high standard but in the end Professor Geissmann and Professor Collin were awarded funding for their project.
Professor Peter Beverley explained: “We received some very high quality applications and had great difficulty in choosing a recipient but in the end, we felt that Professor Geissmann and Professor Collins’s project matched all of our criteria and will hopefully take forward existing knowledge about LCH.”
The three-year project will cost just over £327,000 and will be funded by The H R Trust and The Artemis Association of Greece.
This will be the third project that has been funded by The Trust. The first project, led by Professor Hans Acha-Orbea, aimed to identify genes that are switched on when normal dendritic cells, which are closely related to Langerhans Cells, become tumours. The study took place at the University of Lausanne, Switzerland.
The Trust’s second project, which is still ongoing, is looking at the Development of Gene Therapy for Familial Haemophagocytic Lymphohistiocytosis (HLH) due to perforin deficiency. Scientists Bobby Gaspar and Adrian Thrasher together with Dr Marlene Carmo are working on replacing Perforin, the commonest gene to cause inherited HLH.