Knock out blood protein drug signals possible new treatment for Alzheimer`s and diabetes

Scientists at UCL have developed a drug to treat a serious medical condition linked to Alzheimer`s disease and type 2 diabetes. The research, supported by the Medical Research Council (MRC) and reported in NATURE, is the culmination of 25 years of basic and clinical research and the UCL scientists hope that it may be the key to the treatment of other serious diseases.

Crucially, Professor Mark Pepys and his team have managed for the first time to remove from the human body a naturally occurring blood protein – known as SAP – that is linked to development of the disease.

Amyloidosis – a disorder in which the body`s own proteins accumulate as abnormal fibres that damage organs and tissues leading to disease – claims the lives of 1,000 people in the UK every year. All parts of the body can be affected. Also amyloid deposits localised to the brain are associated with Alzheimer`s disease and those in the pancreas with type 2 diabetes.

The research team, based at the UCL Centre for Amyloidosis and Acute Phase Proteins at the Royal Free Hospital, first showed that SAP from the blood contributes to amyloid deposition by sticking to amyloid fibres. They then set out to produce a drug to prevent this. Working with Roche, a new drug called CPHPC was developed that blocks the sticking of SAP to amyloid.

The NATURE research reveals how the new drug was developed and outlines the mechanisms that cause SAP to be removed from the blood. The drug glues pairs of SAP molecules tightly together and the resulting clump of protein is then promptly removed from the blood by the liver and destroyed. Disappearance of SAP from the blood greatly speeds up the removal of SAP from the amyloid deposits in the tissues. Importantly, the research means that CPHPC can also be used to remove SAP from amyloid deposits in the brain in Alzheimer`s disease. The first clinical studies in Alzheimer patients are about to start.

Patients with systemic amyloidosis have already been treated with CPHPC for almost a year. There have been no side effects and their clinical condition has remained encouragingly stable.

Speaking today, Professor Pepys said: `Our experimental studies identified SAP as a key suspect in the development of amyloidosis and we aimed to find a drug that could block its effects.’

`Remarkably our drug produces a complete knockout of the single protein in the blood that we targeted. It`s the first time that this has been achieved with a small molecule drug. Understanding the way the drug works suggests applications of the mechanism we have discovered to other proteins in the blood that contribute to many different diseases.`

Professor Pepys continued: `Although amyloid deposits are closely associated with Alzheimer`s disease and maturity onset diabetes, it is not known whether they actually cause these diseases. But there is no doubt that our work offers real hope for systemic amyloidosis, a very serious conditions which, until now, has been difficult and dangerous to treat.`