The DESPIAD clinical trial: testing a new approach to treatment of Alzheimer’s disease

The first clinical trial of a completely novel and unprecedented approach to modifying the progression of Alzheimer’s disease has opened in London. The study is being conducted in the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Clinical Research Facility at the Leonard Wolfson Experimental Neurology Centre at Queen Square.

The DESPIAD trial will test whether a drug that removes a protein, called serum amyloid P component (SAP), from the brain is helpful in patients with Alzheimer’s disease.

The menacing scourge of Alzheimer’s disease is increasing as populations age in developed countries and also as life expectancy increases in the developing world.

The summit meeting of the G8 group of countries on 11 December 2013 issued a clarion call ‘Declaration on Dementia’, committing to find a cure or disease modifying treatment by 2025.

Alzheimer’s disease is the most common cause of dementia. Dementia affects more than 35 million people worldwide. This number is expected to almost double every 20 years.

The social and economic burden of Alzheimer’s disease is greater than for any other condition. The estimated annual worldwide cost of informal, social and direct medical care for dementia is more than US$400 billion.

Despite investments of billions of dollars and conduct of many large scale clinical trials over the past 20 years, no effective treatments have yet emerged.

Almost all medications tested have been focussed on the abnormal fibrous protein accumulations, known as amyloid plaques and neurofibrillary tangles, which are always present in the brain in Alzheimer’s disease. The drugs have aimed at removing and/or preventing the formation of these abnormal deposits.

There is good evidence that the proteins forming the abnormal fibres are closely related to development of the disease but nobody actually knows for sure what directly causes the death and loss of brain cells that leads to dementia.

The laboratory of Professor Sir Mark Pepys has been working on amyloid for more than 40 years. He has focussed on a normal, non-fibrous protein, called serum amyloid P component (SAP), which is always associated with amyloid fibres in the body. He has shown that SAP contributes to the formation of amyloid and its persistence in the tissues.

In addition, SAP itself, unrelated to its role in amyloid, damages brain cells. The brain in Alzheimer’s disease contains more SAP than normal because of the binding of SAP to the plaques and tangles. It is therefore possible that SAP directly causes death of brain cells leading to dementia.

In order to target SAP and prevent its harmful effects, Professor Pepys, Director of the Wolfson Drug Discovery Unit at the Royal Free Campus of University College London, developed a drug, called miridesap,
which removes SAP from the blood. Miridesap has been given for up to several years to patients with various diseases over the past 18 years, with no significant adverse effects. Because SAP is not made in the brain, removing the protein from the blood with miridesap also removes all the SAP from the brain and from the amyloid deposits in the brain.

The National Institute for Health Research (NIHR), via the NIHR Biomedical Research Centre at University College London Hospitals, has lately funded the essential clinical trial required to determine whether miridesap treatment is helpful in patients with Alzheimer’s disease. The ‘Depletion of serum amyloid P component in Alzheimer’s disease’ trial, known as DESPIAD, is led by Professor Martin Rossor, who is also the NIHR National Director for Dementia Research.

The study has now started in the NIHR Clinical Research Facility at the Leonard Wolfson Experimental Neurology Centre, Queen Square, assisted by the Pharmacy Department of the Royal Free Hospital.

DESPIAD will recruit patients with mild Alzheimer’s disease who will each be treated for one year and tested for changes in brain structure and function. The trial will run for about 3 years. The study is active and open to recruitment but is limited to 100 participants.

This non-commercial trial is sponsored by University College London and entirely funded by the National Institute for Health Research; manufacturing assistance is provided by GlaxoSmithKline.

Source: UCLH