Alzheimer's disease (AD), the commonest cause of dementia, represents one of the greatest health challenges facing the Western world as people live longer and the number of people affected by Alzheimer's increases. There are no existing treatments that slow the relentless progression of dementia caused by AD. A recent announcement from pharmaceutical company Eli Lilly gives hope that we may be on the threshold of a new era in treatments for this devastating neurodegenerative disease.
The existing treatments for AD work by altering the disturbed chemical balance in the brain, increasing levels of neurotransmitters such as acetylcholine. They provide a small boost to cognitive function but do not prevent the progressive damage to synapses and brain function caused by the disease, and with time these treatments become less effective as cognitive function declines.
Billions of pounds of research from industry and academia have failed to identify a safe and effective treatment to slow the progression of the condition – a so-called disease-modifying therapy.
Alzheimer's disease is associated with a build up of a 'sticky' protein in the brain – called amyloid, or Abeta – that damages synapses which allow nerve cells to communicate with each other - to form new memories for example. This build up of amyloid eventually leads to death of nerve cells and shrinkage of the brain with decline in memory and cognitive function that constitutes dementia.
The reason for the for the difficulty in identifying an effective disease-modifying therapy is probably partly due to the fact that the early stages of Alzheimer's start slowly and insidiously, and by the time the condition causes significant symptoms, much of the damage to the brain has already occurred and treatments may be too late. Studies suggest that the initial build of amyloid in the brain may start 25 years before diagnosis, so recent research has focused on treating people in the early and pre-symptomatic phases of AD, before extensive damage to brain cells has occurred.
Solanezumab, the Eli Lilly treatment, is one of a new generation of monoclonal (manufactured) antibodies which targets the Abeta protein that builds up to form amyloid deposits in the brain. When given by regular (monthly) intravenous infusion it binds to the Abeta protein and removes it, reducing build up in amyloid deposits.
Initial trials of Solanuzemab yielded negative results with no apparent benefit as compared to placebo infusions in patients with Alzheimer's. However, analysis of only patients with mild Alzheimer's symptoms showed a slowing of progression of about one third compared to affected people not receiving treatment. This finding led to an extension study in which all patients with early stage AD continued treatment with Solanuzemab. The results of this extension study were reported this week at the Alzheimer Association International Conference. The researchers reported a relatively mild slowing of progression of cognitive decline associated with use of Solanuzemab and hailed this as showing a disease-modifying effect of the drug.
This is welcome news as it is proof of principle that antibodies targeted against Abeta have the potential to slow progression of Alzheimer changes in the brain when given early on in the condition. A larger study of over 2000 patients with early stage Alzheimer's disease is currently in progress and results should be available in 2016.
Solanuzemab and similar drugs will not be available for clinical use for some years as further clinical studies are required to prove whether they are effective and safe. Moreover it is hoped that a new generation of treatments will have a greater effect than the relatively small benefit demonstrated in this study. However, this announcement may mean a corner has finally been turned in the race to develop an effective treatment for Alzheimer's disease.