UCL study discovers potential therapeutic target for Alzheimer's
15 April 2009
Research led by Professor Mark Pepys FRS (Director of the UCL Centre for Amyloidosis and Acute Phase Proteins) has identified a protein known as serum amyloid P component (SAP) as a possible therapeutic target in Alzheimer's disease.
In collaboration with pharmaceutical group Roche, Professor Pepys developed a new small molecule drug, CPHPC, which specifically targets SAP and removes it from the blood. New findings, published in the current issue of PNAS and undertaken by Professor Pepys's team together with Martin Rossor and colleagues from the Dementia Research Centre in the UCL Institute of Neurology, show 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 five individuals for three months. There was the usual depletion of SAP from the blood, seen in all subjects receiving this treatment, but, remarkably, SAP also disappeared 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. Professor Rossor said: "The safety of CPHPC, together with the novel action of the drug in removing SAP from the brain, is very encouraging."
Although the three-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.
Professor Pepys commented: "The complete disappearance of SAP from the brain during treatment with CPHPC could not have been confidently predicted, and the drug, 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.
Images: Professor Mark Pepys (top) and Professor Martin Rossor
Pentraxin Therapeutics Ltd is a company spun out from 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.