Antidiabetic Drugs in Alzheimer’s disease
Today, Dr Grazia Daniela Femminella gives an overview of the potential use of antidiabetic drugs in Alzheimer’s disease, as described in her research article published in Journal of Diabetes Research earlier last month. She is a post-doctoral Clinical Research Fellow at the Imperial College Memory Research Centre, London and has previously held a Research Fellow post at the University of Naples Federico II, Italy. Dr Femminella is a Geriatrician with a specific interest in neurodegenerative diseases with a focus on neuroimaging.
Alzheimer’s disease (AD) is the most common cause of dementia and affects 10% of individuals over the age of 65, rising to over 40% in those aged over 85. It was first described by Dr Alois Alzheimer, a German psychiatrist, in 1906. He identified the hallmarks of the disease, which are abnormal amyloid plaques and neurofibrillary tangles in the brain of AD patients. These abnormal proteins lead to progressive death of nerve cells and loss of brain tissue over time. Most of the patients with AD usually experience problems with their short-term memory as their earliest symptoms, however, as the diseases progresses and larger areas of brain are involved, other symptoms develop, affecting thinking, reasoning, perception or communication.
The reasons why some people develop AD are not yet completely understood. AD is known as a “multifactorial” disease, meaning that a combination of genetic and environmental factors are implied in its onset and progression. There are several genetic factors that increase the risk of a person to develop AD during their lifetime, and both medical conditions and lifestyle habits that can increase its occurrence. Among the medical conditions, diabetes, high blood pressure, stroke, obesity, and high cholesterol are all known to be risk factors for AD. The connection between type 2 diabetes and AD is well known; people with type 2 diabetes are twice more likely to develop AD than healthy people of the same age. In addition, it has been shown that regulation of insulin is abnormal in AD brains.
Even though 400 clinical trials have been carried out in patients with AD in the last decade, there is currently no treatment that can prevent the disease or stop its progression, and the available treatments help marginally with symptom control only. Thus, the need for new drugs is an important priority in AD research.
Given the links between AD and diabetes, medications currently approved for diabetes present a real opportunity for novel therapeutic strategies. At the moment, one large trial is ongoing in the US, testing the efficacy of intranasal insulin administration in AD with a view to issuing a report in 2018.
At Imperial College, London, I am currently working with Dr Paul Edison, who is leading a large multicentre trial (ELAD) where we are evaluating liraglutide in 206 patients with AD. Liraglutide is a drug licensed for the treatment of type 2 diabetes, and it has been shown to reduce nerve cell inflammation as well as abnormal amyloid plaques and neurofibrillary tangles in animal models. Additionally, the drug promotes the formation of new nerve cells and has been shown to protect memory in laboratory studies. Because of these special properties, liraglutide prevents the progressive decline in glucose uptake, indicating that nerve cell function is maintained in the mouse model. These properties of liraglutide make this compound a promising candidate for AD treatment.
The ELAD trial is currently recruiting volunteers in the UK, and we estimate to complete the study by early 2019. It is a privilege for me to work with volunteers with AD, and I am hopeful that a treatment that will stop disease progression will very soon be available to patients and their families.
Opinions in this blog post are that of the author, and not necessarily that of Hindawi. Profile photo credit: Grazia Daniela Femminella. The text in this blog post is by Grazia Daniela Femminella and is distributed under the Creative Commons Attribution License (CC-BY). Illustration by Hindawi and is also CC-BY.