Landmark trial for novel Alzheimer’s disease treatment
This story was first published on the NIHR website.
The first clinical trial of a completely novel and unprecedented approach to modifying the progression of Alzheimer’s disease has opened at the NIHR University College London Hospitals (UCLH) Clinical Research Facility.
The Depletion of serum amyloid P component in Alzheimer’s disease (DESPIAD) trial will test whether a drug called miridesap removes a protein associated with the disease from the brain and slows its development.
This essential trial is funded by the NIHR University College London Hospitals Biomedical Research Centre and led by Professor Martin Rossor, NIHR National Director for Dementia Research.
Alzheimer’s disease is the most common cause of dementia. Dementia affects more than 35 million people worldwide, with this number expected to almost double every 20 years. Despite investments of billions of pounds and many large scale clinical trials over the past 20 years, no effective treatments have yet emerged.
People with Alzheimer’s disease develop accumulations of fibrous proteins, known as amyloid plaques and neurofibrillary tangles, in their brains. The plaques are toxic to brain cells and eventually cause their death, leading to the gradual decline in day-to-day memory and other mental functions. Almost all medications developed for the disease have aimed at removing or preventing the formation of these abnormal deposits.
The normal, non-fibrous protein serum amyloid P component (SAP) binds to the abnormal proteins in the brains of patients with Alzheimer’s disease and prevents amyloid plaques from breaking down.
Professor Sir Mark Pepys, Director of the Wolfson Drug Discovery Unit at University College London, has shown that SAP contributes to the formation of amyloid and its persistence in tissues. Therefore, preventing SAP from binding amyloid plaques may lead to faster breakdown of the amyloid plaques and so delay the progression of Alzheimer’s disease
In addition, SAP itself damages brain cells, via a mechanism unrelated to its role in amyloid. The brains of people with Alzheimer’s disease contain 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 developed a drug called miridesap, which removes SAP from the blood and stops it from reaching the brain.
Miridesap has been given for up to several years to patients with various diseases over the past 18 years, with no significant adverse effects.
The DESPIAD trial will explore the safety, tolerability and potential effectiveness of miridesap in patients with Alzheimer’s disease. The trial 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.