Alzheimer’s: the long and slow goodbye.
In honor of the late Mary Joseph who past from Alzheimer's disease in 1998.
Alzheimer’s disease was first diagnosed just over 100 years ago, yet it remains an area of high unmet medical need with a heavy burden of care. So where is research taking companies?
Whoever and wherever the patient, Alzheimer’s disease can leave a trail of worn out, broken-hearted relatives as they care for their loved one on a journey that cannot be reversed.
Alzheimer’s is a progressive, irreversible brain disorder with a poorly understood cause and no known cure. It attacks and slowly steals the minds of its victim and brings heartache to the career, often a relative, who must watch their loved one slip away to a loathsome thief.
Symptoms of Alzheimer’s include memory loss, confusion, impaired judgment, personality changes, disorientation and loss of language skills. It is the most common form of irreversible dementia.
In the absence of better therapy, this global health problem will only get worse as populations age. It is estimated there will be over 51 million patients with dementia by 2020.
Understanding the needs of people with Alzheimer’s
Myths and misconceptions about Alzheimer’s
The World Health Organization says Alzheimer’s disease has many myths and misconceptions.
For example, some people regard the disease as the same as ‘going mad’, and others ask about the need to go to a doctor if Alzheimer’s is ‘part of getting old’.
As a director in the Business and Commercial Analysis group of GSK's Research & Development division, one of Jaron Ballentine’s responsibilities is to help the company better understand the needs of patients and physicians so it can develop better medicines.
In the case of Alzheimer’s, however, there is an additional need. “Alzheimer’s is a condition that affects not only the patient but also the career, the patient’s family and society as a whole,” he says.
While the core symptoms are memory and cognition loss, these can lead to other symptoms and physical ailments. "If an Alzheimer’s patient has trouble remembering the names of close friends and answering questions in social situations, chances are that this will eventually result in embarrassing social situations. In turn, this will lead to a lack of confidence and withdrawal," says Jason.
Caring for the care-giver
Alzheimer’s concerns more than the patient, of course. Most have a career or care-giver who takes primary responsibility for their well-being. This person is usually a loved one – over 80 per cent of careers are a partner, spouse or relative, usually a son or daughter. A majority of careers are retired or homemakers; about 30 to 40 per cent have part-time or full-time jobs which place additional burdens on them. The time given to caring has been compared to having another job.
“Regardless of the circumstance, caring for an Alzheimer’s patient takes dedication and self-sacrifice. We are told that 70 per cent of care-givers have
reported they have decreased social activities as a result of being a care-giver. About half of them have limited hobbies or have given them up, and almost ten per cent have changed or given up their job.” This significant care-giver burden is a factor that is now measured in Alzheimer’s trials at GSK. “The hope is that the medicines we are developing for Alzheimer’s will not only benefit the patient but also improve the care-giver’s quality of life.”
Alzheimer’s is a condition that affects not only the patient but also the career, the patient’s family and society as a whole. 
The emotional aspects of Alzheimer’s should not be forgotten. “Most careers are either a husband or wife, or a son or daughter, and they love the patient dearly. They recognize that while it is a significant sacrifice, they feel strongly that they want to take good care of their loved one and ensure they are well cared for and comfortable. It is the family who sees the patient slowly fade away, in what many call ‘the long goodbye’.”
Research directions for Alzheimer’s
So what are companies such as GSK doing to combat this soul-destroying disease?
Current mainstream therapies work by reducing the degradation of the neurotransmitter acetylcholine in the synapse (the region where nerve impulses are transmitted and received between nerve cells). If the level of acetylcholine in the synaptic areas of the brain can be maintained, memory dysfunction can be improved.
”Some of the therapies we are developing modulate and up-regulate the release of neurotransmitters. Other approaches endeavour to mimic the effect of the missing neurotransmitters or increase the response of the receiving cells to those transmitters,” says John Davis, director of one of the Molecular Discovery Research units in GSK's Research & Development division.
Avenue of exploration
The fact that energy metabolism appears to be affected in Alzheimer’s disease is offering GSK a further avenue of exploration. “Drugs that can modulate glucose utilization, like those currently used in diabetes, are a good bet in trying to modulate glucose utilization in the brain,” says John.
“By having a number of symptomatic approaches, we hope to produce new therapies for patients that have improved or different side-effect profiles. We also hope to produce improved efficacy - or at least efficacy that can be added to existing treatments - so that the armoury which physicians have to combat the disease is increased.”
However, the problem with symptomatic treatments is that they do not tackle the underlying progression of the disease. “If a patient’s drug is removed, we may find that their condition deteriorates rapidly in response, so we are also looking for disease-modifying therapies that will tackle the underlying cause of the disease.”
Going back to Alois Alzheimer
As well as having a number of symptomatic treatments in the clinical pipeline, GSK is looking at somehow modifying the disease.
Alzheimer’s facts
- About 18 million people worldwide are estimated to have Alzheimer’s
- More than 50 per cent of people with Alzheimer’s live in developing countries. By 2025, this will be over 70 per cent
- Alzheimer’s can occur at any age, even as young as 30 years
- The total worldwide cost of dementia care is estimated to be US $360.4 billion annually.
- It is currently not possible to predict who will get Alzheimer’s - it can strike anyone irrespective of gender, caste, creed, culture or socioeconomic status
- 21 September marks Alzheimer’s Disease Day, organised by the Alzheimer’s Disease International, an umbrella body for Alzheimer’s groups around the world.
Here, researchers have returned to some of Alois Alzheimer’s original observations, one of which concerns characteristic plaques in the brain. These contain a substance called beta-amyloid, which is thought to be important in the progression of the disease.
GSK is investigating a number of disease modifying approaches that aim to lower amyloid levels in the brain.
Focus on the Alzheimer’s patient
"In the past few years we have been conducting some ground-breaking work using large patient populations to work out how patients can help in developing new therapies and approaches towards delivering drugs," says John.
"On the one hand we have conducted genetic association studies, where we can identify genetic mutations carried in the population that predispose those patients towards contracting or developing Alzheimer’s disease. The other way of using these large banks of data derived from patients is to look for biomarkers of the disease or physiological processes that can be targeted in the pathology of the disease." The hope is that these markers may then be used to manage the development of therapeutics more efficiently.
There are many people, among them the careers and those who are and will be patients, who are hoping the research paths being taken now - 100 years since Alois Alzheimer first described this saddening disease - are fruitful ones.
