Do Alzheimer’s sufferers finally have cause for optimism?
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Version 0 of 1. Every week in my neurology clinic at the Walton Neuro-Centre in Liverpool, I see people who are worried that they may have Alzheimer’s disease. Perhaps this is not surprising, given there is a news story about the disease almost daily, an estimated 850,000 people in the UK have dementia, and the government has described it as “one of the greatest challenges of our lifetime”. This is why news of solanezumab, a drug that appears to slow decline in Alzheimer’s patients, has provoked such interest. Currently, the treatments we can offer patients with Alzheimer’s disease are very limited Determining whether someone has dementia can be a complex business, but in some cases it is relatively straightforward. One patient who tells me she is worried because two weeks ago at 8.30pm she stopped to do some shopping on the way home from the office, but forgot to buy milk, has probably not got dementia. Indeed anyone who can tell me exactly what they forgot is likely to be one of the “worried well”. They are a bit forgetful, maybe over-tired, stressed, and possibly even depressed, but their cognitive function is essentially intact. In contrast, if I ask a patient why they have come to clinic and they look slightly befuddled and turn to the relative sitting next to them for help, this is a pretty good clue that they may well have dementia. Dementia is an umbrella term describing a progressive impairment of the brain’s higher mental functions. It is characterised by changes in memory, behaviour and personality, difficulty thinking and reasoning. Although it has many causes, Alzheimer’s disease is the most common. More than 100 years ago a German doctor, Aloysius Alzheimer, was looking down the microscope at brain tissue from a patient with severe short-term memory loss; he was the first person to describe the amyloid plaques and neurofibrillary tangles that typify the disease. We now know these plaques are short segments of a normal protein that have folded abnormally; the tangles are made from another protein, which has also gone wrong. But whether these abnormal clumps of protein are the cause of the disease, or a consequence of the primary disease process, is not known. Currently, the treatments we can offer patients with Alzheimer’s disease are very limited. The brain is a complex collection of billions of neurons, like a massive telephone exchange sending signals in all directions. Messages are passed down each neuron as electrical currents; chemical neurotransmitters are used to pass the signal across the junction boxes from one neuron to the next. Acetylcholine is one such chemical; and because it is reduced in patients with Alzheimer’s we use drugs to boost its levels. But these current treatments are only sticking plasters that do not deal with the underlying disease process. They typically slow the deterioration in symptoms by only a few months. With the genetically engineered antibody, solanezumab, we may have for the first time a treatment that tackles the amyloid protein critical to the disease. Antibodies are part of our natural protection against things that shouldn’t be there, such as infections, malignant cancer cells and abnormal proteins. The drug was created by injecting mice with amyloid protein so they produce antibodies; then taking the antibody-producing cells and modifying their DNA to make “humanised” antibodies, which can be given to patients. In mice, the antibodies mopped up the amyloid protein and study results indicate that the drug may delay disease progression in humans with Alzheimer’s. Interestingly, the study’s initial reports, published in 2012 showed no benefit overall. But that study included patients with both mild and moderate disease. When patients with mild disease only were analysed, the drug did seem to slow the disease down, and today’s further analysis, which includes more patients, appears to back this up. Related: Alzheimer’s: what the mice are really telling us | David Shariatmadari However, caution is needed before anyone gets too excited. This is a secondary analysis of the data and it is sometimes possible to produce all sorts of results if you work at the data hard enough. The results were presented in the razzmatazz of an international Alzheimer’s conference in the US, where there is a strong lobby for more investment in dementia; the results have not yet undergone the cool, calm scrutiny of publication in a peer-reviewed journal. And none of the other drugs that target the amyloid protein have so far been proved to work; indeed the trial results for a similar antibody, presented at the same meeting, were disappointing. The definitive results of a larger study of solanezumab will be published at the end of 2016. In the meantime, given that Alzheimer’s is a disease for which almost every drug trial ends in disappointment, the fact that these latest results are promising should be cause for quiet optimism for the growing number of people it affects. |