Blog: Developments in the treatment of Alzheimer’s

Particularly of note is the most frequently occurring and best known form of dementia; Alzheimer’s disease. Characterised by loss of memory and personality changes, the condition is caused by the degeneration of neurons in the brain. The two main classes of available treatments focus on two neurotransmitters which are thought to be involved with this neurodegeneration: acetylcholine and glutamate. While these medications are effective in slowing down disease progression initially, they typically do not work for extended periods of time, and a need for more efficacious treatment is evident.

A key aspect of Alzheimer’s disease is the presence of abnormal aggregations of protein in the brain: tangles of a protein named Tau, and plaques formed of mis-folded beta-amyloid. One of the major focuses of Alzheimer’s research in recent years has been using monoclonal antibodies to target beta-amyloid formations. These typically work by binding to the proteins which give rise to amyloid plaques, preventing them from aggregating, or by binding to the plaques themselves and destroying them. While there has been some promising efficacy data in phase II clinical trials, several of the monoclonal antibody therapies are only able to prove statistically significant efficacy in patients who are treated in the very early stages of the disease[2]. This may suggest that while these therapies can reduce the amyloid plaques associated with Alzheimer’s disease, the capacity this has to improve symptoms and prevent further degeneration may be limited.

While several key aspects of the neurodegeneration pathway are becoming better understood, it is important to untangle cause and effect to identify appropriate targets for new medications. A significant amount of research is focused on better understanding these highly complex pathways, and trials such as those with monoclonal antibodies can play an important role in identifying which elements should be targeted. Programmes such as The Connectivity Map[3] (also known as cmap) are enabling researchers to screen the proteins involved in Alzheimer’s disease against a database of currently available medications. Once identified, lab models such as mice can be used to test if a drug could have an effect on the development and progression of neurodegeneration.

As more and more investment and research occurs in the field of dementia, we can hope to see more clinical trials and positive outcomes for new and repurposed medications over the next decade. With the currently high prevalence of Alzheimer’s combined with our aging population, it has been estimated that over 115 million people worldwide will have the condition by 20501.

Therefore any product with a significant improvement on the efficacy of currently available treatments has huge potential both for profit, and for improving the quality of later life for millions of patients.

[1] https://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf
[2] Prins ND, Scheltens P: ‘Treating Alzheimer's disease with monoclonal antibodies: current status and outlook for the future.’ Alzheimer’s Research & Therapy. November 29 (2013)
[3] https://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=2967 ;