The Centre conducts world leading research in all aspects of the pentraxin family of plasma proteins, and in amyloidosis. Studies range from molecular, genetic, biochemical, physiological and pathological investigations to clinical diagnostics, patient management and new drug discovery. There are extensive collaborative links with scientists, clinicians and industry in many of these areas. The goal is to elucidate fundamental normal and pathobiological mechanisms in order to improve diagnosis, management and outcome of disease. Apart from all aspects of amyloidosis, for which the UK NHS National Amyloidosis Centre is located in this Department, there are particular interests in inflammatory diseases, as well as the major common diseases associated with local amyloid deposits: Alzheimer's disease and type 2 diabetes mellitus.
The National Amyloidosis Centre has provided a diagnostic, staging, monitoring and management advisory service for the national caseload of patients with amyloidosis since it was commissioned by the NHS National Commissioning Group in 1999. The amyloid practice is the world's largest and most diverse, and has introduced specific services for patients with hereditary and age-related cardiac amyloidosis. The Centre also provides genetic, diagnostic and treatment services for patients with hereditary periodic fever syndromes, and is home to the NHS Specialised Services CAPS Treatment Service for children and adults with the cryopyrin associated periodic syndrome (CAPS). More information about the NHS CAPS Treatment Service and about the condition is available on the patient information site.
New inventions for treatment of disease made by Professor Sir Mark Pepys in the Centre are owned by Pentraxin Therapeutics Ltd, the UCL spin-out company that he founded. The Pentraxin Therapeutics Ltd portfolio covers treatments for amyloidosis and amyloid protein associated diseases. All the drug discovery and development work is conducted within the Wolfson Drug Discovery Unit established in the Centre in 2011, with funding from the Wolfson Foundation, when Sir Mark retired as Head of Medicine at the Royal Free Campus. Since 2012, the Unit has received its core funding from the National Institute of Health Research (NIHR) via the UCL/UCLH Biomedical Research Centre (BRC).
Pepys developed a new drug, miridesap (formerly known as CPHPC) that specifically targets SAP and depletes it from the blood and reduces the amount of SAP in amyloid deposits within the tissues. However, it does not remove all the amyloid bound SAP and this observation led Pepys to a new therapeutic invention in 2005. He used miridesap to deplete SAP from the blood while leaving some SAP in the amyloid deposits. Antibodies to SAP can then be given safely and they target the amyloid deposits for destruction and clearance by macrophages, the professional debris-clearing cells of the body. This treatment dramatically clears established visceral amyloid deposits in experimental models and in 2009 it was licensed to GlaxoSmithKline for a collaborative development programme. The first in human clinical trial started in June 2013 and produced unprecedented, safe and effective removal of visceral amyloid deposits in patients with systemic amyloidosis. The results have been published in the N Engl J Med (2015) and Sci Transl Med (2018). Unfortunately GSK subsequently decided that the risk benefit profile of this treatment was unfavourable and terminated development in 2018. Nevertheless, compelling proof of concept has been achieved, showing that antibody treatment can remove amyloid from the tissues with clinical benefit.
The DEpletion of Serum Amyloid P Component In Alzheimer's Disease (DESPIAD) phase 2b clinical trial of miridesap (CPHPC), which depletes serum amyloid P component from the brain (Proc Natl Acad Sci USA 2009; Open Biol 2016) is being conducted in the Leonard Wolfson Experimental Neurology Centre at the UCL Institute of Neurology. It is sponsored by UCL and funded by the NIHR via the UCLH/UCL BRC with additional support from Alzheimer's Research UK and the Dana Foundation of New York. Professor Martin Rossor FMedSci, the NIHR National Director for Dementia Research, and Professor Sir Mark Pepys FRS FMedSci are the principal investigators. The trial started in September 2018 and will run for at least 3 years.