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Types of treatments being researched

Clinical trials

Researchers approach dementia from different angles depending on their interests as well as their understanding, theories and models of dementia. The objectives of their research may also differ. Some may be trying to find a way to prevent or delay the onset of the disease, whereas others may be interested in trying to slow down its progression or treat the symptoms. A few research areas are very briefly described below.

Research area

Explanation of how drug or treatment would or does work

Acetylcholinesterase inhibitors
(existing drugs include Exelon, Reminyl and Aricept)

People who have Alzheimer’s disease seem to have less acetylcholine in their brains than other people. Acetylcholine is a neurotransmitter (a chemical produced in the brain which acts as a kind of messenger between brain cells). Once acetylcholine has been produced and used in the brain, it is broken down by acetylcholinesterase (special enzymes). This is a natural process which is repeated over and over again.

However, as people with Alzheimer’s disease no longer produce as much acetylcholine as they used to, drugs containing acetylcholinesterase inhibitors have been developed which interfere with the breaking down of their limited supply of acetylcholine. Three such drugs have already been authorised but clinical trials are still being conducted for these drugs (e.g. for different types of dementia, different combinations of the drug and different doses or ways to administer them).

NMDA receptor antagonists
(e.g. Memantine)

Brain cells, which are damaged as a result of Alzheimer’s disease and some other forms of dementia, can lead to some cells releasing too much glutamate (a chemical which carries messages between brain cells). The glutamate then sticks to “docking sites” (known as N-methyl-D-aspartate receptors) on these cells and this allows too much calcium to get into the cell which further damages brain cells. Drugs known as N-methyl-D-aspartate (NMDA) receptor antagonists stick to the same docking sites thereby preventing the glutamate from attaching itself and letting too much calcium in. As with the acetylcholinesterase inhibitors, clinical trials for the NMDA receptor antagonist are still being conducted.

(e.g. RemberTM, Divalproex)

Tau is a protein which accumulates in the brains of people with Alzheimer’s disease. It results in the build up of brain lesions made up of neurofibrillary tangles (short fragments of the tau protein) which are the hallmarks of Alzheimer’s disease. This happens long before the symptoms of the disease start to show. Researchers are interested in finding ways to stop these neurofibrillary tangles from accumulating e.g. by dissolving the tau tangle filaments before they start to form the tangles.

Example of a study involving tau:

Rember is a drug, currently under trial, which it is claimed inhibits the aggregation of tau protein. Its active ingredient is methylthioninium chloride (MTC). This is better known as methylene blue (which is a deep blue dye used in biology to stain tissue and in certain industrial products such as ink). Initial results demonstrated a slowing down of the progression of AD in people with mild AD who took the drug over a 50 week period. Further trials (phase 3) were initiated, also in order to investigate whether the drug could prevent the formation of the disease in the first place.

(e.g. Flurizan, Myrian, PBT2)

Beta-amyloid, another kind of protein, also accumulates in the brains of people with Alzheimer’s disease. It is a kind of sticky protein which accumulates in the brain in the form of protein fragments. Beta-amyloid is produced by a larger protein called the beta-amyloid precursor protein (APP). These protein fragments are naturally broken down and eliminated but this does not happen in people with Alzheimer’s disease. Consequently, the fragments accumulate and form hard, insoluble plaques which are hallmarks of Alzheimer’s disease.

Research efforts have concentrated on trying to prevent the formation of beta-amyloid plaques and on trying to eliminate them from the brain.

Synapse function
(e.g. Souvenaid)

People with Alzheimer’s disease lose a significant amount of brain synapses and this loss tends to correspond to a loss of cognitive abilities. Researchers are looking into ways to improve synaptic formation and synaptic transmission which would then prevent or compensate for this loss. This might eventually be in the form of a specific treatment or perhaps a nutritional supplement.

(e.g. Pittsburgh Compound-B)

Biomarkers capable of tracking the presence of Alzheimer’s disease in plasma and cerebrospinal fluid (CSF), for example, constitute another line of research. This could involve various scanning techniques or even blood samples which are then analysed in the laboratory. Some scanning techniques can detect minute changes in the structure of the brain which are linked to the rate and extent of brain loss (i.e. speed of loss and volume of loss).

The ability to identify biomarkers could eventually help doctors identify individuals who are at risk of developing Alzheimer’s disease and to monitor patients’ response to treatment more effectively.

Examples of studies involving CSF:

Researchers at Washington University of School of Medicine St Louis, took a first set of samples of CSF from people with mild Alzheimer’s disease and a second sample, three and a half years later. Levels of beta-amyloid and phosphorated tau 181 were monitored and compared to the observed rate of decline. This kind of study is important as it may contribute towards the identification of people at particular risk of a steep decline in cognitive abilities and also help monitor the effectiveness of drugs in preventing or slowing down the progression of dementia.

In another study, three types of data were analysed: 1. CSF and ratios of AD-related proteins, 2. MRI volume measures of certain sections of the brain and 3. scores on tests measuring memory, learning and brain function. The participants in the study were either healthy or had Alzheimer’s disease or amnestic mild cognitive impairment. The researchers, from Trinity College, Dublin, found that when the various types of data were combined it was possible to distinguish with 94% accuracy the participants who progressed from MCI to AD versus healthy people. The researches state that the model needs to be validated by an autopsy study of the AD cases.

(e.g. Bapineuzumab, ACC-001, Intravenous immunoglobin IVIg)

Researchers have been trying for some time to develop a vaccine capable of stimulating an immune response to amyloid protein in the brain. Unfortunately, problems linked to meningoencephalitis (inflammation of the brain) in one study led to the research being halted. Nevertheless, passive immunization is now also being explored as a possible alternative method (e.g. Bapineuzumab) whereby antibodies are contained in the drug rather than generated by the body.

A study involving IVIg:

Researchers from the Mount Sinai School of Medicine, New York analysed the medical records of 847 people who had received at least one treatment of IVIg (for other conditions such as cancer) over four years and 84,700 who had not. They found that people who had received IVIg had a significantly lower risk of developing Alzheimer’s disease compared to those who had not received IVIg. A large scale clinical trial is now underway to determine whether IVIg could be an effective treatment for Alzheimer’s disease.

Drugs currently used for other conditions
(e.g. Dimebon)

Sometimes, there is sufficient evidence to suggest that a drug used to treat one medical condition might be effective in the treatment of another condition. This was the case for Dimebon. It was originally marketed in Russia as an antihistamine drug but was found to improve the function of mitochondria (the central energy source of all cells). This is important for AD as an impairment of the mitochondrial function is believed to play a significant role in the loss of brain cell function in AD.



Last Updated: vendredi 21 août 2009




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