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Fighting Alzheimer’s disease? Get the immune system on board

James Fuller

James Fuller

James Fuller discusses his research into developing antibodies against Alzheimer’s disease in the third and final highly commended article for the Max Perutz Science Writing Award 2012.

Imagine living with the knowledge that over the next decade your brain will be slowly destroyed by your own body. As neurons are snuffed out like candles, what will you lose next? Will it be precious memories? The ability to perform an everyday task? Perhaps a facet of your personality? Your family and friends will have to watch helpless as the person they love is slowly eroded away.

Imagine now finding out that with all of our medical expertise there is nothing we can do. Not one treatment that can slow the course of this deterioration. This is a reality for someone diagnosed with dementia.

Alzheimer’s disease is the most common form of dementia with an estimated 20 million sufferers worldwide, incurring a £400 billion cost to healthcare services. These figures are already frightening, but our population is getting older and the number of people with dementia will double in 30 years. The only way to prevent this is to develop new drugs to combat this devastating condition. Current therapies work by increasing certain chemicals in the brain; allowing neurons to function but not stopping them from dying. Despite a lot of research and trials of potential drugs not one therapy has been found that can slow the rate at which neurons die.

So, what is holding us back from developing these new therapies? There are many problems but perhaps the biggest is that we do not fully understand how this disease works, and how to model the disease in the lab. This may be the reason why so many drugs have failed in clinical trials — clearly what we need are new approaches. By looking at the blood or brains of patients we can get an idea of what goes wrong in Alzheimer’s disease and therefore design potential new treatments.

From these studies we now know that a protein called Aβ for an unknown reason builds up in the brain of Alzheimer’s patients, forming large clumps called plaques. One idea suggests that the buildup of these plaques causes the destruction of neurons, and therefore removal of these plaques could protect the neurons from dying. As a result of this observation, therapies are being developed to break up these deposits or reduce the amount of Aβ produced.

One of the most effective and revolutionary ideas has been to “vaccinate” Alzheimer’s patients against these plaques. This is a very similar process to what happens when you are vaccinated against a disease like tuberculosis (TB). The TB vaccine teaches your immune system to recognise and remember a dead version of the bacteria which causes the disease.

This means that when you encounter the real bacteria, immune cells can fight off the infection. During this process, antibodies are being produced that bind to the bacteria; the immune system is then activated to engulf and destroy the antibody-coated bacteria preventing you from getting ill.

At this point you may be wondering; what does this have to do with Alzheimer’s disease?

Scientists can produce antibodies in the lab that bind to almost anything: a virus, a cancer cell or even the plaques we find in the brains of Alzheimer’s patients. When an Alzheimer’s patient is treated with an antibody that binds to plaques, these deposits become coated in the antibody. The subsequent immune response clears the patient’s brain of these potentially dangerous plaques.

Fantastic, so we can now use these antibodies to help patients? Well not quite… while the antibody efficiently clears the plaques from the brain, the success has been tempered by side effects. To remove the antibody-coated plaques it is necessary to activate cells from the immune system and this can cause inflammation in the brain. While this inflammation is actually helpful in removing bacteria such as TB, inflammation in the brain can have severe consequences.

Inflammation in Alzheimer’s patients occurs around blood vessels in the brain causing damage and bleeding, potentially inducing further deterioration and memory loss. For my PhD project I am developing new antibodies to prevent these nasty side effects. By making tiny adjustments to the structure of antibodies we can control how the immune system responds to the therapy. We are hoping that these new antibodies remove the plaques without inducing further damage to the brain.

Advances in healthcare have greatly increased the length of time we live, however the quality of life we experience in our older years has not increased at the same rate. Dementia is one of science’s biggest challenges and the problem will only get worse if new therapies are not found soon.

Harnessing the power of the immune system using antibodies may be one of these therapies, and this has already been an effective strategy in the treatment of bacterial infections, cancer and rheumatoid arthritis. If we could make this form of therapy safe for the treatment of Alzheimer’s disease, it would be a good step forward to reduce the suffering of millions of patients worldwide.

James Fuller

James is a PhD student at the University of Southampton.

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