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Amyloidosis and acute phase proteins: world-leading clinical service
12 December 2014
The UCL Centre for Amyloidosis and Acute Phase Proteins conducts world-leading research that has rapidly fed through to patient care. This includes advances in the diagnosis of amyloidosis and clinical characterisation of many new subtypes that has led to new standards of clinical care, improved diagnosis, improved outcomes, and major investment by the NHS.
Amyloidosis is a disorder characterised by organ failure resulting from the accumulation of protein as abnormal fibres. There are various types including those arising as a result of long-standing inflammation (AA amyloidosis) or a consequence of myeloma, a haematological malignancy, (AL amyloidosis) or in association with ageing (ATTR amyloidosis). Highlights of the extensive clinical research programme in amyloidosis at UCL that have led to better management of amyloidosis patients include:
Understanding of key aspects of hereditary amyloidosis. Until UCL's genetic study, hereditary systemic amyloidosis was thought to be incredibly rare and to affect only a few dozen families worldwide. Most affected patients either remained undiagnosed or were incorrectly assumed to have AL amyloidosis resulting in needless and harmful chemotherapy. The study of 350 patients identified a hereditary cause in 10% of cases, resulting in genetic testing being introduced in the NHS National Amyloidosis Centre as a new standard of care. UCL has subsequently identified more than 100 patients with hereditary renal amyloidosis, and have characterised the phenotype, diagnostic pathway and role of organ transplantation in this subtype.
During the past 15 years it has at last become possible to diagnose amyloidosis accurately and determine its consequences throughout the body, enabling treatment in almost all patients. - Professor Philip Hawkins
Design and introduction of powerful new diagnostic imaging methods. UCL researchers invented a new method to image amyloid deposits in vivo and enable quantification and characterisation of amyloid in sites throughout the body. The team has also developed methods for imaging and evaluating cardiac amyloid deposits of transthyretin (ATTR) type to enable diagnosis and clinical management of elderly patients with this hitherto very difficult to diagnose disorder. UCL researchers were also the first to systematically demonstrate the utility of cardiac magnetic resonance imaging (CMR) in 2005, and have subsequently developed specific CMR methods to characterise and quantify cardiac amyloid deposits of all types.
Major advances in monitoring of disease and therapy. UCL has led and participated in major international collaborative studies that have evaluated and defined the clinical utility of various biomarkers to stage severity of disease and monitor response to treatment in AL amyloidosis, the most common and serious type of the disease. These findings have now been adopted throughout the world, both for specialist clinical practice and in clinical trials. UCL clinical studies of cyclic multiple agent chemotherapy have defined current best practice for the majority of AL amyloidosis patients who are not fit enough to undergo stem cell transplantation.
The NHS National Amyloidosis Centre (NAC) was established by Professor Philip Hawkins and Professor Sir Mark Pepys (UCL Centre for Amyloidosis and Acute Phase Proteins) in 1999 to provide diagnostic and clinical management services for the national caseload of patients with amyloidosis. UCL research findings put into practice through the Centre has underpinned steady improvement in mortality and outcome measures.
For example, refined use of serum free light chain measurements has greatly improved monitoring of responses to chemotherapy in AL amyloidosis. UCL research has also demonstrated the feasibility and limitations of solid organ transplantation in amyloidosis. With careful selection, approximately 2% of patients receive an organ and outcomes match those in general transplant registries; renal transplantation in AL amyloidosis, the most serious type, has doubled during the past five years. Almost all patients with AL amyloidosis attending the Centre now benefit from combination chemotherapy regimens that include the novel proteasome inhibitor agent, bortezomib. This and other new high-cost, high-efficacy drugs, licensed in the past six years for treatment of myeloma, are available on the NHS to almost all patients with AL amyloidosis as a direct result of UCL's published clinical research work, which completely changed the chemotherapy paradigm. Five year survival of AL amyloidosis patients under the care of the National Amyloidosis Centre has improved substantially during the past 12 years, from 34% in the period 2001-2003 to 50% in 2008-2012.