New therapeutic approaches in Alzheimer's disease are urgently needed. Work led by Professor Mark Pepys FRS over more than 20 years has identified a protein known as serum amyloid P component (SAP) as a possible therapeutic target in Alzheimer's disease. In collaboration with Roche he developed a new small molecule drug, CPHPC, which specifically targets SAP and removes it from the blood. In the exciting new work reported now in the PNAS, the Pepys team together with Professor Martin Rossor and colleagues from the Dementia Research Centre of UCL's Institute of Neurology, have shown that the drug also removes SAP from the brains of patients with Alzheimer's disease.
In this first study of the drug in patients with Alzheimer's disease, CPHPC was given to 5 individuals for 3 months. There was the usual depletion of SAP from the blood, seen in all subjects receiving this treatment, but also remarkable disappearance of SAP from the brain. Laboratory tests revealed the molecular mechanism responsible for this unique effect and also disclosed for the first time the way in which SAP accumulates in the brain in Alzheimer's disease.
Administration of CPHPC and the removal of SAP had no side effects in the patients with Alzheimer's disease. CPHPC has also been given for several years to patients with other diseases without any adverse effects. "The safety of CPHPC, together with the novel action of the drug in removing SAP from the brain, is very encouraging", said Professor Rossor.
Although the 3 month treatment period was too short to show any clinical benefit there was no obvious deterioration. Longer and larger scale clinical studies are being planned to confirm safety and seek evidence of benefit to the patients.
"The complete disappearance of SAP from the brain during treatment with CPHPC could not have been confidently predicted" said Professor Pepys, "and the drug, also to our surprise, entered the brain. Coupled with the absence of any side effects, these new findings strongly support further clinical studies to see whether longer term treatment with CPHPC protects against the inexorable mental decline in patients with Alzheimer's disease."
In December 2008 Roche divested CPHPC entirely to Pentraxin Therapeutics Ltd, a UCL spin out company founded by Professor Pepys. In February 2009 Pentraxin Therapeutics Ltd licensed CPHPC to GlaxoSmithKline for treatment of systemic amyloidosis, a rare fatal disease. Pentraxin retains the rights to CPHPC for all other indications.
Publication: Molecular dissection of Alzheimer disease neuropathology by depletion of serum amyloid P component
Simon E. Kolstoea,1, Basil H. Ridhab,1, Vittorio Bellottia,2, Nan Wangd,3, Carol V. Robinsond, Sebastian J. Crutchb, Geoffrey Keirc, Riitta Kukkastenvehmasb,4, J. Ruth Gallimorea, Winston L. Hutchinsona, Philip N. Hawkinsa, Stephen P. Wooda, Martin N. Rossorb, Mark B. Pepysa,4
aCentre for Amyloidosis and Acute Phase Proteins and the National Amyloidosis Centre, Division of Medicine (Royal Free Campus), University College London Medical School, London NW3 2PF, UK; bDementia Research Centre, Department of Neurodegeneration, and cDepartment of Neuroinflammation, Institute of Neurology, University College London Medical School, London, WC1N 3BG, UK; dDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
About Pentraxin Therapeutics
Pentraxin Therapeutics Ltd is a company spun out from University College London (UCL) by UCL Business PLC (UCLB) to hold and develop the intellectual property of Professor Mark Pepys and his colleagues in the UCL Centre for Amyloidosis and Acute Phase Proteins. This clinical and basic science research centre houses the UK NHS National Amyloidosis Centre and it leads the world in research and clinical management of amyloidosis (www.ucl.ac.uk/medicine/amyloidosis).
About UCL
Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. UCL is the seventh-ranked university in the 2008 THES-QS World University Rankings, and the third-ranked UK university in the 2008 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Marie Stopes, Jonathan Dimbleby, Lord Woolf, Alexander Graham Bell, and members of the band Coldplay. UCL currently has over 12,000 undergraduate and 8,000 postgraduate students. Its annual income is over £600 million.
UCL Business PLC
UCL Business PLC (UCLB) is the organisation responsible for commercialising research across all disciplines, generated from within UCL and associated organisations. It is primarily responsible for protecting inventions and transacting commercial activity including options, licences and collaborative commercial research. UCLB also has responsibility for creating and spinning-out companies from UCL. UCLB is wholly-owned by UCL and operates as an independent company with its own Board of Directors.
For more information contact: Professor Mark Pepys +44 20 7433 2786
Journal
Proceedings of the National Academy of Sciences